We Are What We Eat: Food Safety and Proteomics - American ...

REVIEWS pubs.acs.org/jpr

We Are What We Eat: Food Safety and Proteomics Angelo D’Alessandro and Lello Zolla* Department of Ecological and Biological Sciences, Tuscia University, Largo dell’Universita snc, 01100 - Viterbo, Italy ABSTRACT: In this review, we lead the reader through the evolution of proteomics application to the study of quality control in production processes of foods (including food of plant origin and transgenic plants in particular, but also meat, wine and beer, and milk) and food safety (screening for foodborne pathogens). These topics are attracting a great deal of attention, especially in recent years, when the international community has become increasingly aware of the central role of food quality and safety and their influence on the health of endconsumers. Early proteomics studies in the field of food research were mainly aimed at performing exploratory analyses of food (bovine, swine, chicken, or lamb meat, but also transgenic food such as genetically modified maize, for example) and beverages (wine), with the goal of improving the quality of the end-products. Recently, developments in the field of proteomics have also allowed the study of safety issues, as the technical advantages of sensitive techniques such as mass spectrometry have guaranteed a faster and improved individuation of food contaminating pathogens with unprecedented sensitivity and specificity. KEYWORDS: food safety, proteomics, mass spectrometry, quality controls

1. FOOD SAFETY: WHY DOES IT MATTER? “You are what you eat” is a famous and provocative statement by Ludwig Feuerbach that mocks the idealistic notion of man as Homo sapiens and points to the naturalistic foundation of our existence.1 Apparently, the German philosopher was but the precursor of the modern “new-age”-permeated holistic view of biology. It is thus small wonder that, over the last decades, food safety and quality control in all production processes have growingly attracted a great deal of attention. Speaking in more general terms, the individuation of standard quality criteria has become a pivotal step in the agenda of international companies and institutions from clinical routine practice to alimentary industry products, both aiming at guaranteeing top quality standards for end-user consumers. Food safety itself might be implicit in the broader concept of food security, which is defined as a situation in which all people at all the time have physical and economic access to sufficient, safe, and nutritious food to meet their dietary needs and live an active healthy life.2 In short, food security is a three step process, and depends on: (i) the availability of food; (ii) overall access to the available food; and (iii) proper use of the accessed food.2 Food safety encompasses each one of the three aspects. In times of world economic crisis, the romantic linkage between food and people described by Feuerbach has gradually shifted toward a more pragmatic one between food and health and, ultimately, between food and the costs behind a welfareadequate healthcare system. Recent analyses on healthcare conditions pinpointed at the balance between costs and quality.3 As Brezis and Wiist debated in a recent review, the participation of for-profit healthcare industries in the main healthcare systems r 2011 American Chemical Society

such as in the U.S. might fuel the trend toward increasing costs at the expenses of the patients, especially from poorer, sicker or least educated social classes.3 These considerations prompted the need to improve prevention rather than curing diseases in order to cut costs for the medical expenses. During the last decades, it became evident to the mainstream culture that food might be pivotal in the natural prevention of a wide number of diseases.4 This widespread conviction stems from the scientific evidence that numerous clinical, physiopathological and epidemiological studies have underlined the detrimental or beneficial role of nutritional factors in complex inflammation-related disorders such as allergy, asthma, obesity, type 2 diabetes, cardiovascular disease, rheumatoid arthritis and cancer (for a complete review the interested reader is referred to D’Alessandro et al.5). Therefore, a correct lifestyle based upon physical exercise and good alimentary habitudes have rapidly become a cornerstone in western education seeking to pose, for example, a firm challenge to obesity, an actual plague for the new generations especially in the U.S. and in Italy.6,7 In recent years, food safety is an increasingly broadening concept which encompasses mainly three main areas: (i) food quality (food composition); (ii) traceability (food origin); (iii) food safety per se (absence of allergens, pathogens or other contaminants). Indeed, food safety is not only a matter of determining the origin of a product, but it is also to evaluate Special Issue: Microbial and Plant Proteomics Received: September 2, 2011 Published: October 12, 2011 26

dx.doi.org/10.1021/pr2008829 | J. Proteome Res. 2012, 11, 26–36

Journal of Proteome Research

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Figure 1. Proteomics has recently found several applications in the monitoring of food safety, especially of food of plant origin. Several aspects can be monitored through proteomics: from (A) food traceability to the determination and positive selection of (B) those quality traits that confer resistance to abiotic stresses such as drought, cold, flood or osmotic stress. Another important facet is the application of proteomics to the assessment of the principle of substantial equivalence between food from (C) genetically modified plants and wild type counterparts. Last, but not least, the sensitivity and specificity of the mass spectrometry-based proteomics approaches allows for revealing traces of (D) contaminating agents, such as E. coli bacteria in soybean sprouts.

food edibility through biochemical assessment of product purity, both under a chemical and microbiological standpoint. As for the latter, a warning sign might be represented by the recent epidemy of mutant E. coli which has involved the north of Germany and almost paralyzed vegetable commerce within Europe at the beginning of June 2011. Early attempts to individuate quality standards through biomolecules mainly relied on rough biochemical parameters, such as product composition (for examples through labeling of percentages of lipids, carbohydrates, proteins and vitamins). Recent advancements in the fields of biochemistry and molecular biology allowed us to look for actual biomarkers to be potentially exploited as indicators of product quality and traceability.8,9 In this frame, proteomics has already contributed to accumulating a relevant body of knowledge, which might result not only in improving food safety through enhancing selection of food quality and traceability markers but also in providing the end-user consumer with a unique tool to make a fully aware alimentary choice. Both of these concepts (traceability and quality) represent funding values in the international community, which continuously strives for the valorization of local products in each country, although the need to meet food safety standards poses international challenges about the individuation of shared strict standards for production processes in the alimentary pipeline. In this review, we will focus on the role held by proteomics research in the individuation of quality markers of most various foods, from meat to vegetables, of biological or transgenic origin. We will then give a glance at the recent introduction of emerging techniques for the individuation of microbial food contaminations.

valorize local cultivars worldwide, although the introduction of quantitative and redox proteomics techniques have contributed valuable information as well.10 Plant and cultivar peculiarities in food quality (and quantity) is also relevant in the light of the need to meet the demand for safe, sufficient and nutritious food for everyone from the international food security agenda. In other terms, local cultivars with peculiar resistances to abiotic stresses11 14 have attracted a great deal of interest in the field of plant proteomics since they might represent a biological clue to the need of increasing food productivity worldwide, especially in those areas where the climate makes it difficult to fulfill a self-sustaining plant production politics. Plant proteomics analyzing plant responses to abiotic stresses include (i) responses to drought stress;15 (ii) to flooding stress;16 (iii) to salinity and osmotic stress;17,18 (iv) to cold stress;19,20 (v) to heat stress;21 (vi) plant response to radioactive contamination;22,23 and (vii) plant resistance to heavy metal exposure.24 The determination of the characteristics at the protein level that render one specific cultivar resistant to a specific stress might result fundamental in the choice to export it in those areas where adverse environmental conditions hamper cultivation or result in poorer harvests. Such an approach enables artificial selection of natural species, while on the other hand recent advancements in the field of recombinant DNA technology allowed direct manipulation of DNA of local cultivars to boost their natural growing performances, thus increasing either productivity or natural resistance to abiotic stresses. In plant science, recombinant DNA technology is often combined with other techniques for the introduction of DNA using cultured cells and tissues which are pivotal for transferring selected elite trait genes from a plant into another plant or nonrelated plant species in order to create genetically modified crops.25 Since the first commercialization of genetically modified tomatoes in 1994, the land area of planted genetically modified crops has increased almost one hundred fold to reach 148 million hectares (representing about 10% of total arable land on the planet) across 29 countries in 2010.26 Most of the genetic modification have been aimed so far at conferring traits for tolerance to total herbicides or resistance to insects, which helped increasing crop yields and reducing chemical use and soil impacts.26 Genetically modified plants have not only been designed to improve productivity, but also to improve quality of plant-derived food. Several studies showed promising

2. VEGETABLES AND CROPS When dealing with food safety in plants, there are several considerations to take into account. Safety of food of plant origin includes (i) the determination of protein biomarkers for food traceability (and thus, for example, the presence of allergens in cultivars from specific regions); (ii) the possibility to highlight eventual differences between wildtype plants and transgenic plants; and (iii) the absence of pathogens from biological or abiotic contaminants (e.g., microbiological contaminants such as toxins, or chemical contaminants such as heavy metals) (Figure 1). As for the first point, explorative proteomic studies have largely contributed to accumulate background knowledge to 27

dx.doi.org/10.1021/pr2008829 |J. Proteome Res. 2012, 11, 26–36


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applications of nutritionally enhanced genetically modified crops such as enrichment in β-carotene, vitamin E, omega-3-fatty acids or iron,27 while genetic modifications which might result in improved resistance to stresses are still under experimentation.25 Food safety and quality control become two funding principles in the alimentary industry when it comes to genetically modified organisms. Over recent years, it has become clear that food and feed plants carry an inherent risk of contaminating our food supply.28 The current procedures to assess the safety of food of genetically modified plant origin include the investigation of possible unintended effects (expression of allergens, for example) which might be deleterious to the end user consumers.29 To improve the probability of detecting unintended effects, profiling techniques such as proteomics are currently tested as complementary analytical tools to the existing safety assessment. In order to understand the importance of these tools in quality control of food from either wild type and recombinant plants, it could be worthwhile to recall the concept of “substantial equivalence”, according to which a novel food (for example, food derived from genetically modified organisms) should be considered the same as and as safe as a conventional food if it demonstrates the same characteristics and composition as the conventional food (OECD, 1991).30 The recombinant DNA technology approach, other than holding some ethic concerns about the comparison between natural and transgenic cultivation, also implies the fascinating molecular question of whether altering the DNA of a specific cultivar ultimately results in the modification of only one character or of the whole proteome. Several studies have sought to provide a temptative answer to this question. In 2008, Zolla et al. have proposed a comparison of proteomics profiles between wild type and seeds from genetically modified maize plants.31 The authors analyzed the proteomic profiles of one transgenic maize variety (event MON 810) in two subsequent generations (T05 and T06) with their respective isogenic controls (WT05 and WT06). Thus, by comparing the proteomic profiles of WT05 with WT06, the environmental effects were determined, while the comparison between WT06 and T06 seeds from plants grown under controlled conditions enabled Zolla’s group to investigate the effects of DNA manipulation.31 The Authors evidenced a differential expression of approximately 100 total proteins, the expression levels of which were altered as a consequence of the environmental influence (WT06 vs WT05). On the other hand, 43 proteins resulted in up- or downregulation in transgenic seeds with respect to controls (T06 vs WT06), which could be specifically related to the insertion of a single gene into a maize genome by particle bombardment.31 One of the most striking conclusions from this study was that transgenic seeds responded differentially to the same environment as compared to their respective isogenic controls, as a result of the genome rearrangement derived from gene insertion.31 Proteomics assessment of food safety in the field of transgenic maize has been also complemented by metabolomics approaches.32 The metabolic profiles of seeds from the transgenic maize variety 33P67 and of the corresponding traditional variety were also investigated using NMR techniques.32 About 40 water-soluble metabolites in the maize seed extracts were identified. The 1H spectra of transgenic and nontransgenic seed maize samples turned out to be conservative, allowing one to asses that no significant differences in metabolic profile exist between transgenic maize and traditional variety.32

It appears that substantial equivalence should be assessed at multiple levels, since proteomics might provide some clues that are not necessarily tied to other biological parameters, such as metabolism. Another important facet of proteomics application to food safety in plants is about plant diseases and microbial contamination. Plant diseases can be devastating for human health, both directly, if plant toxins are consumed, and indirectly, if plant diseases result in crop loss and subsequent malnutrition.33 For example, the yield loss to wheat crops from one race of wheat stem rust (Ug99) typically ranges from 40 to 80%, with some instances of complete crop failure.33 Some longstanding plant health problems, such as mycotoxins and ergotism, continue to add significantly to the health burden, especially of infants, and cause widespread problems with basic foodstuffs. Particularly vulnerable to these problems are the world’s approximately 850 million people who are not able to obtain sufficient food to lead healthy and productive lives.33 As for contaminations, the number of documented outbreaks of human infections associated with the consumption of raw fruits, vegetables, and unpasteurized fruit juices has increased in the last decades. According to the Centers for Disease Control and Prevention, in the U.S. the number of reported produce-related outbreaks per year doubled between the period 1973 1987 and 1988 1992.34 36 During both time periods, the etiologic agent was unknown in more than 50% of outbreaks. Outbreaks with identified etiology were predominantly of bacterial origin, primarily Salmonella. More recently, salmonellosis has been linked to tomatoes, seed sprouts, cantaloupe, mamey, apple juice, and orange juice.37 Escherichia coli O157:H7 infection has been associated with lettuce, sprouts, and apple juice, and enterotoxigenic E. coli has been linked to carrots.37 Documented associations of shigellosis with lettuce, scallions, and parsley; cholera with strawberries; parasitic diseases with raspberries, basil, and apple cider; hepatitis A virus with lettuce, raspberries, and frozen strawberries; and Norwalk/Norwalk-like virus with melon, salad, and celery have been made. Among the greatest concerns with human pathogens on fresh fruits and vegetables are enteric pathogens (e.g., E. coli O157:H7 and Salmonella) that have the potential for growth prior to consumption or have a low infectious dose.38 A mandatory first step in the strive against bacterial contamination is prevention. To limit the introduction of pathogenic bacteria through irrigation (preharvest steps), the origin and distribution of irrigation water, as well as the history of the land, should be known.38 Postharvest sources of contamination are not to be a priori excluded since they include feces, human handling, harvesting equipment, transport containers, wild and domestic animals, insects, dust, rinsewater, ice, transport vehicles, and processing equipment.38 While prevention is a necessary first step, quality control and microbial safety assessment is no second. In this frame, decades of microbial proteomics39 have recently found a valid application in the field of food technology and biotechnology.40 Investigations using protein based analysis to trace food borne pathogens have been reported more frequently over the last five years. Given the extreme sensitivity and specificity, proteomics technologies could be potentially applied to the (i) identification of microbial food contaminants; (ii) the detection of microbial toxins in food; (iii) monitoring of cleaning and sanitation processes; (iv) the prediction of the cellular response to environmental change.40 28



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Milk quality is also affected by mastitis,51 which is rather frequent in intensive dairy farming (especially of high-milk yielding cows such as Holstein Friesian). This background knowledge on bovine milk, but also sheep,52 goat53 and donkey milks,54 can be ultimately exploited to improve cheese production quality.55 However, to better evaluate the influence of proteomics profile to cheese organoleptic properties, it is worthwhile to stress the role of proteins released by the bacterial ecosystem of Lactobacilli and their region specific strain.56

While approaches to microbial food safety have been purported through electrophoretic techniques,41 actual progresses have been recently made through the build up and application of protein databases through mass spectrometry which allow the identification of microorganisms and substrains through a fully automated process. Indeed, big strides in the field of mass spectrometry-application to microbiology are still defining an ongoing revolution which might spread its benefits to the food safety endeavor as well: the introduction of Bruker Daltonics’ MALDI-Biotyper.42 This technology allows for rapid and >97% accurate identification of bacteria and microorganism (and region-specific strains—overall 468 strains of 92 bacterial species43) cultured from routine clinical samples through the identification of species-specific proteomics profiles. Its application to the field of food safety might result in something more than a suggestive perspective, contributing to the cause of reducing the likelihood of untoward risks raising from the assumption of unsafe food. While this kind of application has been so far only postulated, the possibility to relate MALDI TOF-derived unique proteomic profiles to unique biologic features has been already applied to the traceability of honey obtained from Hawaian bees.44

4. WINE Grapevine (Vitis ssp.) is perhaps the most economy-relevant fruit plant, which holds a relevant role also due to its non climacteric productive attitude.57 A renewed interest in wines and thus in grapevine cultivars over the last decades has stemmed from the observation that French people suffering from coronary heart disease represented but a minor percentage, despite following a diet relatively rich in saturated fats,58 albeit rich in (red) wine consumption: a phenomenon known as the French paradox. Some grape berry proteins are production quality-relevant as they are known to resist fermentation and to cause turbidity in wines. As brilliantly synthesized by Giribaldi and Giuffrida,57 the detailed knowledge of the protein content and characteristics of grape berries and juices is important for winemakers, since protein precipitation is a major cause of haze formation in wines, and especially in white wines. The denaturation and subsequent aggregation of proteins can lead to amorphous sediment or flocculate, causing turbidity. A haze or deposit in bottled wine indicates that the product is unstable, has a low commercial value and is therefore unacceptable for sale, and winemakers usually perform some kind of fining, such as bentonite absorption, to avoid this defect. Conversely, proteins could also be considered as important constituents in wines, for example in the sparkling wine industry, because they promote foam formation and stability. Other than representing a likely production quality-limiting factor, some of the proteins detected both in wine and grape berries, such as Chitinase and lipid transfer protein, are known to be allergenic.59 61 In this respect, a further burden is represented by treatments with fining agents, which have been traditionally used in winemaking despite being also allergenic (e.g.: albumin, casein). However, caseins are also known as major food allergens and therefore, according to the Directive 2007/68/EC of the European Community (EC), “any substance used in production of a foodstuff and still present in the finished product” must be declared in the label, especially if it originates from allergenic material. Nonetheless, it is technically impossible to quantify any residual casein below the detection limit set by the EC (200 μg/L via indirect ELISA assay). Preliminary low-abundance protein enrichment strategy such as combinatorial peptide ligand libraries prior to electrophoresis have been adopted by Righetti’s group to reveal casein concentrations as low as 1 μg/L in wines.62,63 Proteomics has been applied in wines to detect either the presence of fining agents or wine-specific proteins. The majority of wine proteins are in the range of 20 30 kDa.61 Flamini and De Rosso have recently reported the application of different mass spectrometry (MS) techniques to study of grape and wine proteins.61 By liquid chromatography (LC) electrospray ionization (ESI) MS and nano-LC MS, 9 dipeptides and 80 peptides

3. MILK AND CHEESE Milk is one of the richest physiological liquids, whose function has always been tied to the provision of nutrients to offspring. In recent decades, milk has been growingly suggested to contribute to postnatal development of the newborn, through stimulation of its anatomical growth, maturation of its immune system, completion of its digestive tract, and the establishment of symbiotic microflora.45 Proteomics application to milk studies has rapidly become an eligible approach, since the protein fraction constitutes perhaps the most biologically relevant component in milk. While qualitative and quantitative information about animal milk provides relevant nutritional hints, a complete annotation of the bovine and human milk proteome for example has contributed fundamentally to the creation of artificial milk formulas for those infants that cannot be breastfed for any biological reason.45 47 Among milks, bovine milk has the longest history and the broadest commercial interest. Indeed, bovine milk consumption is of extreme importance to humans, as Enattah and colleagues concluded upon the observation that lactase persistency and cattle domestication have almost convergently evolved in most human populations.48 Bovine milk proteins, present at a concentration of 32 g L 1, are generally classified as caseins (80% of the total milk protein content), whey proteins (16%), peptones/low molecular weight peptides (3%) and milk fat globule membrane (MFGM) proteins (1%), and proteomics studies addressing each one of the subfractions have been extensively performed and reviewed.46 The determination of proteins in bovine milk has evident consequences in the alimentary industry other than for milk formulas. For example, it is possible to understand whether feeding the animal with a specific diet ends up influencing milk yield and composition, or rather test the presence of post-translational modifications such as glycosylation (O- and N-glycosylation) and lysine lactosylation differential patterns.49 The latter consideration holds relevant consequences in the frame of milk safety, since anomalous glycosylation or lactosylation profiles might trigger allergic responses in the consumer.50 29



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Figure 2. Proteomics application to food quality and safety contributes to (A) food traceability, which allows valorizing regional products. It also allows determination of (B) adulteration of food, as it is possible to discriminate meat from different animals given their proteomics profiles. (C) Microbial and parasite contamination is a relevant concern for meat food as well. (D) Determination of proteomics profiles allows for improving selection strategies for specific qualitative trait loci, as for example in the discrimination between beef cows and dairy cows, as in the case of Chianina and Holstein Friesian breeds. Analogously, it may help discriminating between qualitative traits yielding lean and high fat deposing pigs, thus improving organoleptic properties through positive selction of those traits. (E) Possibility of discriminating species specific protein biomarkers holds potential to reveal the origin of gelling and fining agents as well. (F) Finally, it is possible to understand the influence on meat and milk quality through direct comparison of different farming conditions (e.g., rearing environment, feeding).

were unambiguously identified in Champagne and Sauvignon Blanc wines, respectively. Using matrix-assisted laser desorption/ ionization (MALDI) time-of-flight (TOF) and surface-enhanced laser desorption/ionization TOF, the protein and peptide fingerprints in Chardonnay, Sauvignon Blanc and Muscat of Alexandria wines were determined.61 The authors reported that MALDI-TOF analyses allowed the identification of the mesocarp proteome of six Vitis grape varieties.61 Proteiomics has been also applied to study the extracts from different grape tissues upon exposure to pathogens.61 The major grape pathogenic-related

proteins were chitinases and thaumatin-like proteins, which were supposed to persist through the vinification process and thus cause hazes and sediments in bottled wines.61 Additional applications of proteomics to wine analysis have been reported in the literature, including the determination of the proteomics profiles in grape upon infection with Botrytis cinerea,64 the determination of yeast protein contaminants in white, red and rose wines,65 the determination of glycoproteomics profiles in red wines which are likely to influence protein stabilization and potential allergenic cross-reactivity.66 30



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Table 1. Milestones in SOD Biochemistry: A Historical Perspective authors

ref

year

brief description

Ashraf

15

2010

A critical review introducing the relevance of proteomics research in the study of plant resistance to drought stress.

Kong et al.

16

2010

Differentially expressed cell wall proteins were detected under flooding stress to wheat roots through gel-based

Proteomics on food of plant origin

proteomic and LC MS/MS-based proteomic techniques. Eighteen proteins were found to be significantly regulated in response to flood by gel-based proteomics and 15 proteins by LC MS/MS-based proteomics. Toorchi et al.

17

2009

Protein profiles from soybean plants treated with polyethylene glycol (PEG - as a model for osmotic stress) were

Wang et al.

18

2009

High resolution of proteome reference maps of S. europaea shoot were performed as to obtain evidence on the salt

monitored by a proteomics approach. 37 differential proteins were identified upon PEG treatment. tolerance mechanism by analyzing the proteomic responses of this plant to high salinity. Results demonstrated that significant variations existed in 196 out of 1880 protein spots detected on 2-DE gels. Rinalducci et al.

19

2011

A proteomics investigation on long-term responsiveness and the evaluation of the effects of cold exposure of an Iranian

Rinalducci et al.

20

2011

A study on the influence of both optimal and low temperatures on growth and development in a vernalization-requiring

Aghaei et al.

21

2008

A proteomics investigation of the effects of high salinity to potato crops (Kennebec and Concord cultivars), the

spring wheat (cv. Kohdasht). winter wheat (Triticum aestivum L. cv Cheyenne) after prolonged times of treatment. main abiotic stress for this crop. 47 proteins were differentially expressed under NaCl treatment in shoot of both Danchenko et al.

22

2009

cultivars. Plant adaptation mechanisms toward permanently increased level of radiation using a quantitative high-throughput proteomics approach. Soybeans of a local variety (Soniachna) were sown in contaminated and control fields in the Chernobyl region. Mature seeds were harvested and the extracted proteins were subjected to 2-DE. In total, 9.2% of 698 quantified protein spots on 2-D gel were found to be differentially expressed.

Klubikova et al.

23

2011

A proteomic approach to flax seed development in the remediated Chernobyl area. A quantitative approach (2-DE and

Fagioni et al.

24

2009

Basal and apical leaves of spinach were tested through proteomics upon cadmium exposure.

Zolla et al.

31

2008

Proteomics analysis of wild-type and genetically modified maize seeds to assess the principle of substantial equivalence at the protein level.

Piccioni et al.

32

2009

Metabonomics analysis of wild-type and genetically modified maize seeds. While proteomics indicated the likely

MS/MS) yielded differential expression profiles for 379 2-DE spots through seed development.

nonsubstantial equivalence of these samples, NMR-based metabolomics did not show major deviations. Microbial identification Washburn

39

2000

A thorough review on the advancements in the field of microbial proteomics.

Gaso-Sokac et al.

40

2010

A comprehensive review on the application of proteomics in food technology and biotechnology for quality controls.

García-Ca~ nas

41

2007

An exhaustive and critical review, discussing CE methods developed to detect and identify contaminants of microbial

et al. Seng et al.

42

2009

origin, including toxins, that represent a hazard to humans in foods. MALDI Biotyper technology for the (99% confidence) identification of microbial species through mass spectrometry.

Sogawa et al.

43

2011

MALDI Biotyper-based identification of 468 strains of 92 bacterial species with >97% confidence.

Wang et al.

44

2009

MALDI Biotyper application to the traceability of honey produced by Hawaian bees. Milk proteomics

D’Alessandro

45

2010

et al.

A review cataloguing a referenced list of proteins discovered in milk through proteomics and targeted protein-oriented investigations (Western blot and protein arrays) which encompasses the differences and similarities between human and bovine milk proteomes. This thematic data set might be useful for preparation of milk formulas for nonbreastfed infants.

D’Alessandro et al

46

2011

A review enlisting a total of 578 unique protein entries from all bovine milk fractions. A role is proposed for bovine milk proteins in triggering anatomical and immune system development of the lactating calf and, indirectly, of the bovine

Hettinga et al.

47

2011

The aim of this study was to study the difference in the host defense proteome of human and bovine milk. Human and

milk fed child. bovine milk were analyzed through a shot-gun proteomics approach, while focusing on host defense-related proteins. In total, 268 proteins in human milk and 269 proteins in bovine milk were identified. Of these, 44 from human milk and 51 from bovine milk were related to the host defense system. Of these proteins, 33 were found in both species but with significantly different quantities. Arena et al.

49

2010

A combination of proteomic procedures based on analyte capture by combinatorial peptide ligand libraries, selective trapping of lactosylated peptides by m-aminophenylboronic acid-agarose chromatography and collision-induced dissociation and electron transfer dissociation MS was used for systematic identification of the lactosylated proteins in milk samples subjected to different thermal treatments. 31



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Table 1. Continued authors

ref

year

brief description

Hogarth et al.

51

2004

Whey from dairy cows with clinical mastitis was compared to whey from healthy animals by 2-DE and MALDI MS analysis.

Pisanu et al.

52

2011

An optimized protein extraction method was applied to sheep milk fat globule membrane fraction, and extracts were subjected to SDS-PAGE separation followed by shotgun LC tandem mass spectrometry for identification and characterization of 170 proteins.

D’Auria et al.

53

2005

Proteomics characterization of milk obtained from different mammalian species in order to understand the mechanisms

Cunsolo et al.

54

2011

Proteomics of donkey milk, which is today categorized among the best mother’s milk substitute for allergic newborns.

behind allergy to cow’s milk. Through the use of combinatorial peptide ligand library technology, and treating large volumes (up to 300 mL) of defatted, decaseinized (whey) milk, the Authors have been able to identify 106 unique gene products. Johnson and

55

2006

Lucey

A review about the role of milk proteomics in the improvement of cheese production. Genomics and proteomics have increased the likelihood of the development of nonstarter adjuncts with specific enzymatic activity. The use of adjunct microorganisms has been designed as to produce cheese with a unique flavor profile.

Gagnaire et al.

56

2004

Analysis of proteins secreted by Lactobacili in Emmental cheese. Proteomics analyses documented stress responses triggered by thermophilic lactic acid bacteria and Propionibacterium strains at the end of ripening. Information was also obtained regarding the origin and nature of the peptidases released into the cheese, thus providing a greater understanding of casein degradation mechanisms during ripening. Different peptidases arose from Streptococcus thermophilus and Lactobacillus helveticus, suggesting that streptococci are involved in peptide degradation in addition to the proteolytic activity of lactobacilli. Grapevine and wine proteomics

Giribaldi and

57

2010

Giuffrida

An extensive review on proteomics application to the analysis of grapevine cultivars. Proteomics approaches to the investigation of grapevine proteins are reported, with a particular focus on 2007 papers onward, since the completion of the mapping of the Vitis ssp. genome.

Ferreira et al.

59

2002

Proteomics of allergens in grapevine berries: a review.

Flamini and De Rosso

60

2006

By liquid chromatography (LC) electrospray ionization (ESI) MS and nano-LC/MS, nine dipeptides and 80 peptides were unambiguously identified in Champagne and Sauvignon Blanc wines

Cereda et al.

62

2009

Proteomics analysis of wines enriched through combinatorial peptide ligand libraries to detect traces of fining agents.

D’Amato et al.

63

2010

Proteomics analysis of red wines enriched through combinatorial peptide ligand libraries to detect traces of fining agents. Although the typical levels of casein found range between 45 to 85 μg/L, in one case as little as 3.8 μg/L of casein could be detected, an extremely high level of sensitivity, close to our lower detection limit of 1 μg/L reported for white wines.

Cilindre et al.

64

2008

2DE-MS analysis of wine proteins upon infection with Botrytis cinerea, in order to detect proteomics changes upon

Wigand et al.

65

2009

A total of 121 tryptic peptides were identified, which were attributed to 12 grape proteins and 6 proteins derived from yeast in white, red and rose wines.

Palmisano et al.

66

2010

A total of 28 yeast glycoproteins and 44 glycosylation sites were identified in white wine,which are likely to influence wine

infection: most of the identified differential proteins were from grape origin

stability and allergenic properties. Meat food proteomics Picard et al.

69

2010

Proteomics for the identification of meat quality traits. In this paper, biological markers of meat quality, particularly tenderness in cattle, pigs and fowl are presented, including protein modifications during meat aging in cattle, protein markers of PSE meat in turkeys and of post-mortem muscle metabolism in pigs.

Murgiano et al.

70

2010

D’Alessandro

71

2011

et al.

Proteomics analysis for the identification of protein markers for the selection of local meat quality traits in pigs with different fat deposing attitudes, namely high-fat deposing Casertana and typical Large White breed. Differential proteomics and metabolomics analysis of meat from pigs with different fat deposing attitudes. The integration of proteomics, metabolomics and quality traits such as Minolta values, post mortem pH, water holding capacity has been exploited to obtain correlation matrices for meat quality prediction through biochemical parameters.

Sentandreu et al.

72

2010

A proteomic-based method is proposed for the detection of chicken meat within mixed meat preparations. The procedure comprises the extraction of myofibrillar proteins, enrichment of target proteins using OFFGEL isoelectric focusing, in-solution trypsin digestion of myosin light chain 3, and analysis of the generated peptides by LC MS/MS. Using this approach, the Authors reported detection of 0.5% contaminating chicken in pork meat with high

Leitner et al.

73

2006

confidence. Detection of adulteration of meat soybean proteins through chromatography and mass spectrometry. Soybean proteins are frequently added to processed meat products for economic reasons and to improve their functional properties. Monitoring of the addition of soybean protein to meat products is of high interest due to the strict regulations forbidding or limiting the amount of soybean proteins that can be added during the processing of meat products. 32



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Table 1. Continued authors

ref

year

Grundy et al.

74

2007

brief description Determination of species origin for gelling agents. The reported method was based on the detection of species-specific marker peptides, fibrinopeptides, released from the blood protein fibrinogen during gelling of the blood protein by thrombin. The fibrinopeptides were isolated from foods spiked with commercial bovine binding agent by acid precipitation followed by enrichment using solid-phase extraction and analyzed by liquid chromatography electrospray ionization triple quadrupole mass spectrometry.

D’Alessandro

75

2010

et al.

A review enlisting existing knowledge about egg yolk and white proteins. Redundant proteins were excluded, while isoforms of the same proteins were maintained to reach a total of 260 distinct gene products for egg yolk and 148 for egg white having a match in the database.

Lee and Kim

76

2010

Detection of egg protein traces in food products. Protein-based immunochemical methods, including ELISA as an initial screening quantitative analysis and immunoblotting, were very sensitive and specific in detecting potentially allergenic egg residues in processed foods in trace amounts. In contrast, the proteomics-based, MALDI-TOF MS and LC tandem quadrupole time-of-flight MS methods were not able to detect some egg allergens, such as ovomucoid, because of its nondenaturing property under urea and trypsin.

Leduc et al.

77

1999

This study was aimed at detecting antigens and allergens in egg-white byproduct ingredients and after their incorporation in processed pork meat pastes. Masked egg-white allergens were recognized by human serum IgE after pasteurization. Egg-white antigens were detectable in sterilized meat by ELISA techniques.

Della Donna

78

2009

Detection of traces of growth performance enhancing agents in bovine sera. A multivariate MALDI-TOF-MS proteomics platform was developed using bovine serum samples. Univariate and multivariate discrimination models were capable to identify calves undergoing illicit treatments through beta-2-glycoprotein.

spectrometric approaches.72 This field of applied research has been fueled by the observation of differential protein patterns in meat from different animals, which allows easing the task of those agencies targeting adulteration frauds. Adulteration of meat has been also performed through the addition of proteins of nonanimal origins, such as soybean proteins. In this field as well, mass spectrometry-based proteomics has provided some clues.73 Mass spectrometry-based methods have been also established for example to assess the addition of porcine or bovine gelling agents to porcine, bovine, lamb or chicken meat, which is of clear commercial interest, especially in light of religious issues on certain meat consumption.74 The expansion of proteomics knowledge about egg yolk and white75 has prompted the possibility to highlight through mass spectrometry or immunohistochemistry the presence of traces of protein allergens of egg origins in food76 and meat products,77 respectively. Proteomics application to the study of contaminated meat is not only a matter of microorganisms or adulteration with meat/ gelling agents from other species, but it also involves detection of performance enhancing agents, which are illegally used in cattle (especially in young veals) and other meat producing species to increase food conversion and lean meat production.78

5. MEAT AND MEAT QUALITY When dealing with food safety, it is worthwhile to recall the worldwide alarms for safe meat consumption in relation to Creutzfeld-Jakob (mad cow) disease, avian flu and, more recently, to swine flu. A 2011 study by Price’s group evidenced that a sampling of grocery store meat in five U.S. cities showed that a type of drug-resistant bacteria, Staphylococcus aureus, was contained in about one-quarter of beef, chicken, pork and turkey for sale.67 Besides, surveys conducted by the National Antimicrobial Resistance Monitoring System (NARMS) indicate that retail meat and poultry products are frequently contaminated with multidrug-resistant Campylobacter species, Salmonella species, Enterococcus species, and Escherichia coli.68 Meat safety and quality represent a mandatory issue in the healthcare system agenda (Figure 2) but also for alimentary industries, for which safer and better quality meat might translate into a broader market and higher incomes. Early attempts to apply genomic and proteomics to meat science have sought to provide breeder with the determination of specific traits to be exploited in the selection processes during intensive farming to the end of improving meat quality69 or valorizing regional breeds while maintaining the organoleptic properties of more flavoured meat against the blandness of meat obtained through intensive farming.70,71 The individuation of these traits has allowed increasing food production, although it created new relevant drawbacks including the increased incidence of mastitis in high-yield milk cows or the excess of backfat accumulation in some pig phenotypes such as Mangalica. However, meat safety is not only a matter of food contamination, and proteomics has found proper applications not only in the search for meat quality markers. In the case of meat products, adulteration is a relevant concern, which implies that high quality meat is, at least in part, substituted with lower value meat, resulting in an increased profit for food producers. Different approaches have been used to determine meat authentication, including chromatographic, electrophoretic, and mass

6. NEW PROTEOMIC TECHNOLOGIES AND FUTURE PERSPECTIVES In this review we encompassed all the facets of the concepts behind food safety, including quality, traceability, authenticity, absence of contaminating or adulterating agents (microorganisms or performance enhancing agents in meat, for example), substantial equivalence between food derived from wild type and genetically modified organisms. Most of the contribution of proteomic experts in food research have been so far addressing the quality issue, through the depiction 33



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of the protein portraits of specific aliments, the valorization of local/regional food, or the attempts to determine the mechanisms underpinning resistance to abiotic stresses as in plant research (Table 1). The explosion of recombinant DNA technologies over the last 10 years has prompted concerns about the evaluation of the risks incoming from the consumption of food derived from transgenic organisms. In this view, proteomics offers investigative tools that have been seldom adopted, mainly due to the lack of interdisciplinarity of the researcher tackling food safety issues, on the one hand, and proteomics experts, on the other. Where collaborations have been started proficuously, early fruits have already been harvested, although the feeling is that the best is yet to come. The investigations of other facets complementary to genomics and proteomics, such as metabolomics, might become pivotal in the correct interpretation of those phenomena at the molecular level which yield, for example, more flavoured meat rather than a plant that is more resistant to cold stress. In the next few years, the individuation and application of quali-quantitative protein biomarkers might become pivotal also in food testing to determine food safety. While safe food has a relevant meaning for half of the world, it is in the other half that it becomes pivotal, not only in terms of quality, but also quantity. In this respect, one of the main goals of global policies in food security is to guarantee not only safe, but also sufficient, food for all people. The adoption of specific and sensitive techniques such as proteomics might allow maintainance of the delicate balance between safe and unsafe food, especially in the light of the need for a growing bias toward the intensive application of recombinant DNA technology with the end of pursuing genetic modification-triggered improved harvests, which most of the experts envisage as mandatory to pursue those global politics. Therefore, while the first step has been already made, the big stride of proteomics as a routine food safety assessment tool is yet to come. If “we are what we eat” and if the day will ever come when “proteomics will tell us what we eat”, the syllogism will be concluded with the statement that, in the future, “proteomics will tell us who we are”.

(2) World Food Summit, 1996; http,//www.fao.org/wfs/index_en. htm Last accessed on August, 29th 2011 (3) Brezis, M.; Wiist, W. H. Vulnerability of health to market forces. Med. Care 2011, 49, 232–239. (4) vel Szic, K. S.; Ndlovu, M. N.; Haegeman, G.; Vanden Berghe, W. Nature or nurture, let food be your epigenetic medicine in chronic inflammatory disorders. Biochem. Pharmacol. 2010, 80, 1816–1832. (5) D’Alessandro, A.; Rinalducci, S.; Zolla, L. Redox proteomics and drug development. J. Proteomics 2011, DOI: 10.1016/j.jprot.2011.01.001. (6) Ryan, A. S. Exercise in aging, its important role in mortality, obesity and insulin resistance. Aging Health 2010, 6, 551–563. (7) Fazio, G.; Vernuccio, D.; Di Gesaro, G.; Bacarella, D.; D’Angelo, L.; Novo, G.; Novo, S. Obesity, a new pathology to pay attention to in young people. Curr. Pharm. Des. 2010, 16, 463–467. (8) Cairns, D. A. Statistical issues in quality control of proteomic analyses, Good experimental design and planning. Proteomics 2011, 11, 1037–1048. (9) Aldred, S.; Grant, M. M.; Griffiths, H. R. The use of proteomics for the assessment of clinical samples in research. Clin. Biochem. 2004, 37, 943–952. (10) Baginsky, S. Plant proteomics, concepts, applications, and novel strategies for data interpretation. Mass Spectrom. Rev. 2009, 28 (1), 93–120. (11) Timperio, A. M.; Egidi, M. G.; Zolla, L. Proteomics applied on plant abiotic stresses, role of heat shock proteins (HSP). J. Proteomics 2008, 71 (4), 391–411. (12) Kosova, K.; Vítamvas, P.; Prasil, I. T.; Renaut, J. Plant proteome changes under abiotic stress - Contribution of proteomics studies to understanding plant stress response. J. Proteomics 2011, 74 (8), 1301– 1322. (13) Qureshi, M. I.; Qadir, S.; Zolla, L. Proteomics-based dissection of stress-responsive pathways in plants. J. Plant Physiol. 2007, 164 (10), 1239–1260. (14) Vij, S.; Tyagi, A. K. Emerging trends in the functional genomics of the abiotic stress response in crop plants. Plant Biotechnol. J. 2007, 5 (3), 361–380. (15) Ashraf, M. Inducing drought tolerance in plants, recent advances. Biotechnol. Adv. 2010, 28 (1), 169–183. (16) Kong, F. J.; Oyanagi, A.; Komatsu, S. Cell wall proteome of wheat roots under flooding stress using gel-based and LC MS/MSbased proteomics approaches. Biochim. Biophys. Acta 2010, 1804 (1), 124–136. (17) Toorchi, M.; Yukawa, K.; Nouri, M. Z.; Komatsu, S. Proteomics approach for identifying osmotic-stress-related proteins in soybean roots. Peptides 2009, 30 (12), 2108–2117. (18) Wang, X.; Fan, P.; Song, H.; Chen, X.; Li, X.; Li, Y. Comparative proteomic analysis of differentially expressed proteins in shoots of Salicornia europaea under different salinity. J. Proteome Res. 2009, 8 (7), 3331–3345. (19) Rinalducci, S.; Egidi, M. G.; Karimzadeh, G.; Jazii, F. R.; Zolla, L. Proteomic analysis of a spring wheat cultivar in response to prolonged cold stress. Electrophoresis 2011, 32 (14), 1807–1818. (20) Rinalducci, S.; Egidi, M. G.; Mahfoozi, S.; Godehkahriz, S. J.; Zolla, L. The influence of temperature on plant development in a vernalization-requiring winter wheat, A 2-DE based proteomic investigation. J. Proteomics 2011, 74 (5), 643–659. (21) Aghaei, K.; Ehsanpour, A. A.; Komatsu, S. Proteome analysis of potato under salt stress. J. Proteome Res. 2008, 7 (11), 4858–4868. (22) Danchenko, M.; Skultety, L.; Rashydov, N. M.; Berezhna, V. V.; Matel, L.; Salaj, T.; Pret’ova, A.; Hajduch, M. Proteomic analysis of mature soybean seeds from the Chernobyl area suggests plant adaptation to the contaminated environment. J. Proteome Res. 2009, 8 (6), 2915–2922. (23) Klubicova, K.; Danchenko, M.; Skultety, L.; Berezhna, V. V.; Hricova, A.; Rashydov, N. M.; Hajduch, M. Agricultural recovery of a formerly radioactive area: II. Systematic proteomic characterization of flax seed development in the remediated Chernobyl area. J. Proteomics 2011, 74 (8), 1378–1384.

’ AUTHOR INFORMATION Corresponding Author

*Tuscia University, Largo dell’Universita snc, 01100 Viterbo, Italy. Tel. +39 0761 357 100; fax +39 0761 357 630. E-mail: [email protected].

’ ACKNOWLEDGMENT A.D.A. and L.Z. have been supported by the “GENZOOT” research program, funded by the Italian Ministry of Agricultural, Food and Forestry Policies (Ministero delle Politiche Agricole, Alimentari e Forestali) and the “Nutrigenomicamediterranea: dalla nutrizione molecolare alla valorizzazione dei prodotti tipici della dieta mediterranea - NUME” project, funded by the Italian Ministry of Agricultural, Food and Forestry Policies (Ministero delle Politiche Agricole, Alimentari e Forestali). ’ REFERENCES (1) Feuerbach, L.; Marx, K.; Engels, F.; Schirmacher, W. Feuerbach’s sensual anthropology and the essence of religion. In German socialist philosophy; The Continuum Publishing Company: New York, 1997. 34



REVIEWS

(44) Wang, J.; Kliks, M. M.; Qu, W.; Jun, S.; Shi, G.; Li, Q. X. Rapid determination of the geographical origin of honey based on protein fingerprinting and barcoding using MALDI TOF MS. J. Agric. Food Chem. 2009, 57 (21), 10081–10088. (45) D’Alessandro, A.; Scaloni, A.; Zolla, L. Human milk proteins: an interactomics and updated functional overview. J. Proteome Res. 2010, 9, 3339–3373. (46) D’Alessandro, A.; Zolla, L.; Scaloni, A. The bovine milk proteome: cherishing, nourishing and fostering molecular complexity. An interactomics and functional overview. Mol. Biosyst. 2011, 7 (3), 579–597. (47) Hettinga, K.; van Valenberg, H.; de Vries, S.; Boeren, S.; van Hooijdonk, T.; van Arendonk, J.; Vervoort, J. The host defense proteome of human and bovine milk. PLoS One 2011, 6 (4), e19433. (48) Enattah, N.S. S.; Jensen, T. G.; Nielsen, M.; Lewinski, R.; Kuokkanen, M.; Rasinpera, H.; El-Shanti, H.; Seo, J. K.; Alifrangis, M.; Khalil, I. F.; Natah, A.; Ali, A.; Natah, D.; Comas, S. Q.; Mehdi, L.; Groop, E.; Vestergaard, E. M.; Imtiaz, F.; Rashed, M. S.; Meyer, B.; Troelsen, J.; Peltonen, L. Independent introduction of two lactasepersistence alleles into human populations reflects different history of adaptation to milk culture. Am. J. Hum. Genet. 2008, 82, 57–72. (49) Arena, S.; Renzone, G.; Novi, G.; Paffetti, A.; Bernardini, G.; Santucci, A.; Scaloni, A. Modern proteomic methodologies for the characterization of lactosylation protein targets in milk. Proteomics 2010, 10 (19), 3414–3434. (50) Wal, J. M. Structure and function of milk allergens. Allergy 2001, 56 (67), 35–38. (51) Hogarth, C. J.; Fitzpatrick, J. L.; Nolan, A. M.; Young, F. J.; Pitt, A.; Eckersall, P. D. Differential protein composition of bovine whey: a comparison of whey from healthy animals and from those with clinical mastitis. Proteomics 2004, 4, 2094–2100. (52) Pisanu, S.; Ghisaura, S.; Pagnozzi, D.; Biosa, G.; Tanca, A.; Roggio, T.; Uzzau, S.; Addis, M. F. The sheep milk fat globule membrane proteome. J. Proteomics 2011, 74 (3), 350–358. (53) D’Auria, E.; Agostoni, C.; Giovannini, M.; Riva, E.; Zetterstr€om, R.; Fortin, R.; Greppi, G. F.; Bonizzi, L.; Roncada, P. Proteomic evaluation of milk from different mammalian species as a substitute for breast milk. Acta Paediatr. 2005, 94 (12), 1708–1713. (54) Cunsolo, V.; Muccilli, V.; Fasoli, E.; Saletti, R.; Righetti, P. G.; Foti, S. Poppea’s bath liquor: The secret proteome of she-donkey’s milk. J. Proteomics 2011, 74 (10), 2083–2099. (55) Johnson, M. E.; Lucey, J. A. Major technological advances and trends in cheese. J. Dairy Sci. 2006, 89, 1174–1178. (56) Gagnaire, V.; Piot, M.; Camier, B.; Vissers, J. P.; Jan, G.; Leonil, J. Survey of bacterial proteins released in cheese: a proteomic approach. Int. J. Food Microbiol. 2004, 94 (2), 185–201. (57) Giribaldi, M.; Giuffrida, M. G. Heard it through the grapevine: proteomic perspective on grape and wine. J. Proteomics 2010, 73, 1647– 1655. (58) Ferrieres, J. The French paradox: lessons for other countries. Heart 2004, 90, 107–111. (59) Ferreira, R. B.; Pic-arra-Pereira, M. A.; Monteiro, S.; Loureiro, V. B.; Teixeira, A. R. The wine proteins. Trends Food Sci. Tech. 2002, 12, 230–239. (60) Flamini, R.; De Rosso, M. Mass spectrometry in the analysis of grape and wine proteins. Exp. Rev. Proteomics 2006, 3, 321–331. (61) Pastorello, E. A.; Farioli, L.; Pravettoni, V.; Ortolani, C.; Fortunato, D.; Giuffrida, M. G.; Perono, L.; Garoffo, L.; Calamari, A. M.; Brenna, O.; Conti, A. Identification of grape and wine allergens as an endochitinase 4, a lipid-transfer protein, and a thaumatin. J. Allergy Clin. Immunol. 2003, 111, 350–359. (62) Cereda, A.; Kravchuk, A. V.; D’Amato, A.; Bachi, A.; Righetti, P. G. Proteomics of wine additives: mining for the invisible via combinatorial peptide ligand libraries. J. Proteomics 2010, 73, 1732– 1739. (63) D’Amato, A.; Kravchuk, A. V.; Bachi, A.; Righetti, P. G. Noah’s nectar: the proteome content of a glass of red wine. J. Proteomics 2010, 73, 2370–2377.

(24) Fagioni, M.; Zolla, L. Does the different proteomic profile found in apical and basal leaves of spinach reveal a strategy of this plant toward cadmium pollution response?. J. Proteome Res. 2009, 8 (5), 2519–2529. (25) Job, D. Plant biotechnology in agriculture. Biochimie 2002, 84, 1105–1110. (26) James, C. Global Status of Commercialized Biotech/GM Crops: 2010, ISAAA Brief No. 42; ISAAA: Ithaca, NY, 2010. (27) Cahoon, E. B.; Hall, S. E.; Ripp, K. G.; Ganzke, T. S.; Hitz, W. D.; Coughland, S. J. Metabolic redesign of vitamin E biosynthesis in plants for tocotrienol production and increased antioxidant content. Nat. Biotechnol. 2003, 21, 1082–1087. (28) Ahmad, A.; Pereira, E. O.; Conley, A. J.; Richman, A. S.; Menassa, R. Green biofactories: recombinant protein production in plants. Recent Pat. Biotechnol. 2010, 4, 242–259. (29) Herman, E. M.; Burks, A. W. The impact of plant biotechnology on food allergy. Curr. Opin. Biotechnol. 2011, 22 (2), 224–230. (30) Ruebelt, M. C.; Lipp, M.; Reynolds, T. L.; Schmuke, J. J.; Astwood, J. D.; DellaPenna, D.; Engel, K. H.; Jany, K. D. Application of two-dimensional gel electrophoresis to interrogate alterations in the proteome of gentically modified crops. 3. Assessing unintended effects. J. Agric. Food Chem. 2006, 54, 2169–2177. (31) Zolla, L.; Rinalducci, S.; Antonioli, P.; Righetti, P. G. Proteomics as a complementary tool for identifying unintended side effects occurring in transgenic maize seeds as a result of genetic modifications. J. Proteome Res. 2008, 7, 1850–1861. (32) Piccioni, F.; Capitani, D.; Zolla, L.; Mannina, L. NMR metabolic profiling of transgenic maize with the Cry1Ab gene. J. Agric. Food Chem. 2009, 57, 6041–6049. (33) International Assessment of Agricultural Knowledge, Science and Technology for Development (IAASTD). Food Safety, Plant and Animal Health: Human Health and Sustainability Dimensions. Available at http://www.agassessment.org/docs/10505_FoodSafe.pdf; last accessed on August 30th, 2011. (34) Hussain, I; Burhan Uddin, M. Study of Microbial Flora on Germinated Wheat and Mungbean Seeds Flour. Int. J. Food Safety 2011, 13, 38–40. (35) Buck, J. W.; Walcott, R. Recent Trends in Microbiological Safety of Fruits and Vegetables. Plant Health Prog. 2003, DOI: 10.1094/ PHP-2003-0121-01-RV. (36) Bean, N. H.; Goulding, J. S.; Daniels, M. T.; Angulo, F. J. Surveillance for foodborne disease outbreaks: United States, 1988-1992. J. Food Prot. 1992, 60, 1265–1286. (37) Beuchat, L. R. Ecological factors influencing survival and growth of human pathogens on raw fruits and vegetables. Microbes Infect. 2002, 4, 413–423. (38) Burnett, S. L.; Beuchat, L. R. Human pathogens associated with raw produce and unpasteurized juices, and difficulties in contamination. J. Indust. Microbiol. Biotechnol. 2001, 27, 104–110. (39) Washburn, M. P.; Yates, J. R., 3rd Analysis of the microbial proteome. Curr. Opin. Microbiol. 2000, 3 (3), 292–297. (40) Gaso-Sokac, D.; Kovac, S.; Josic, D. Application of Proteomics in Food Technology and Food Biotechnology: Process Development, Quality Control and Product Safety. Food Technol. Biotechnol. 2010, 48, 284–295. (41) García-Ca~nas, V.; Cifuentes, A. Detection of microbial food contaminants and their products by capillary electromigration techniques. Electrophoresis. 2007, 28 (22), 4013–4030. (42) Seng, P.; Drancourt, M.; Gouriet, F.; La Scola, B.; Fournier, P. E.; Rolain, J. M.; Raoult, D. Ongoing revolution in bacteriology, routine identification of bacteria by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Clin. Infect. Dis 2009, 49, 543–551. (43) Sogawa, K.; Watanabe, M.; Sato, K.; Segawa, S.; Ishii, C.; Miyabe, A.; Murata, S.; Saito, T.; Nomura, F. Use of the MALDI BioTyper system with MALDI-TOF mass spectrometry for rapid identification of microorganisms. Anal. Bioanal. Chem. 2011, 400 (7), 1905–1911. 35



REVIEWS

(64) Cilindre, C.; Jegou, S.; Hovasse, A.; Schaeffer, C.; Castro, A. J.; Clement, C.; Van Dorsselaer, A.; Jeandet, P.; Marchal, R. Proteomic approach to identify champagne wine proteins as modified by Botrytis cinerea infection. J. Proteome Res. 2008, 7 (3), 1199–1208. (65) Wigand, P.; Tenzer, S.; Schild, H.; Decker, H. Analysis of protein composition of red wine in comparison with rose and white wines by electrophoresis and high-pressure liquid chromatographymass spectrometry (HPLC-MS). J. Agric. Food Chem. 2009, 57 (10), 4328–4333. (66) Palmisano, G.; Antonacci, D.; Larsen, M. R. Glycoproteomic profile in wine: a ’sweet’ molecular renaissance. J. Proteome Res. 2010, 9 (12), 6148–6159. (67) Waters, A. E.; Contente-Cuomo, T.; Buchhagen, J.; Liu, C. M.; Watson, L.; Pearce, K.; Foster, J. T.; Bowers, J.; Driebe, E. M.; Engelthaler, D. M.; Keim, P. S.; Price, L. B. Multidrug-Resistant Staphylococcus aureus in US Meat and Poultry. Clin. Infect. Dis. 2011, 52 (10), 1227–1230. (68) Food and Drug Administration. NARMS retail meat annual report, 2007. Available at: http://www.fda.gov/AnimalVeterinary/SafetyHealth/AntimicrobialResistance/NationalAntimicrobialResistanceMonitoringSystem/ucm164662.htm; last accessed on the August 31, 2011. (69) Picard, B.; Berri, C.; Lefaucheur, L.; Molette, C.; Sayd, T.; Terlouw, C. Skeletal muscle proteomics in livestock production. Brief Funct. Genomics 2010, 9, 259–278. (70) Murgiano, L.; D’Alessandro, A.; Egidi, M. G.; Crisa, A.; Prosperini, G.; Timperio, A. M.; Valentini, A.; Zolla, L. Proteomics and transcriptomics investigation on longissimus muscles in Large White and Casertana pig breeds. J Proteome Res. 2010, 9 (12), 6450–6466. (71) D’Alessandro, A.; Marrocco, C.; Zolla, V.; D’Andrea, M. S.; Zolla, L. Meat quality of the Longissimus lumborum muscle of Casertana and Large White pigs: metabolomics and proteomics intertwined. J. Proteomics 2011, DOI: 10.1016/j.jprot.2011.08.024 . (72) Sentandreu, M. A.; Fraser, P. D.; Halket, J.; Patel, R.; Bramley, P. M. A proteomic-based approach for detection of chicken in meat mixes. J. Proteome Res. 2010, 9 (7), 3374–3383. (73) Leitner, A.; Castro-Rubio, F.; Marina, M. L.; Lindner, W. Identification of marker proteins for the adulteration of meat products with soybean proteins by multidimensional liquid chromatographytandem mass spectrometry. J. Proteome Res. 2006, 5 (9), 2424–2430. (74) Grundy, H. H.; Reece, P.; Sykes, M. D.; Clough, J. A.; Audsley, N.; Stones, R. Screening method for the addition of bovine blood-based binding agents to food using liquid chromatography triple quadrupole mass spectrometry. Rapid Commun. Mass Spectrom. 2007, 21, 2919– 2925. (75) D’Alessandro, A.; Righetti, P. G.; Fasoli, E.; Zolla, L. The egg white and yolk interactomes as gleaned from extensive proteomic data. J. Proteomics 2010, 73 (5), 1028–1042. (76) Lee, J. Y.; Kim, C. J. Determination of allergenic egg proteins in food by protein-, mass spectrometry-, and DNA-based methods. J. AOAC Int. 2010, 93 (2), 462–477. (77) Leduc, V.; Demeulemester, C.; Polack, B.; Guizard, C.; Le Guern, L.; Peltre, G. Immunochemical detection of egg-white antigens and allergens in meat products. Allergy 1999, 54 (5), 464–472. (78) Della Donna, L.; Ronci, M.; Sacchetta, P.; Di Ilio, C.; Biolatti, B.; Federici, G.; Nebbia, C.; Urbani, A. A food safety control low massrange proteomics platform for the detection of illicit treatments in veal calves by MALDI-TOF-MS serum profiling. Biotechnol. J. 2009, 4, 1596–1609.

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