Chicken Origin Research Articles

Erratum to “Diversity and origin of South African chickens” (Poult. Sci. 90(10):2189–2194)

* Agricultural Research Council, Animal Production Institute, Private Bag X2, Irene, 0062, South Africa; † Department of Animal Science, Stellenbosch University, Private Bag X1, Matieland, 7602, South Africa; ‡ Discipline of Animal and Poultry Science, University of KwaZulu-Natal, Private Bag X01, Scottsville, 3209, Pietermaritzburg, South Africa; and § Institute of Farm Animal Genetics, Friedrich Loeffler Institut, Holtystr. 10, 31535 Neustadt-Mariensee, Germany

Antibiotic resistance phenotypes of Salmonella isolates of broiler meat and chicken origin

Bu çalışmada tavuk eti ve tavuk orijinli Salmonella izolatlarında 23 antimikrobiyal ajana karşı dirençlilik fenotiplerinin belirlenmesi amacı ile perakende satış yerleri ve çiftlik örneklerinden elde edilen 64 adet et ve 79 adet tavuk Salmonella izolatı, Şubat 2006 ile Ocak 2009 arasında laboratuvarımızda analiz edildi. Tüm Salmonella izolatlarının, örnek tipi göz önünde bulundurulmaksızın, test edilen antimikrobiyalleden en yüksek direnç oranı ile sırası ile eritromisin’e (%100.0), basitrasin’e (%99.3) ve rifampisin’e (%98.6) olmak üzere en az 4 antimikrobiyale dirençli olduğu belirlendi. Ayrıca, et izolatlarının basitrasin, klindamisin, eritromisin, rifampisin’e; tavuk izolatlarının ise eritromisin, spiramisin, penisilin G, doksisiklin hidroklorür ve tetrasiklin’e %100.0 dirençli olduğu bulundu. Tüm et izolatlarının %82.83’ü 4 ile 7 Çoklu İlaç Direnci (ÇİD) gösterirken, tüm tavuk izolatlarının %55.68’i 10, 12, 15 ve 17 antimikrobiyale ÇİD gösterdiği belirlendi. Et izolatlarında %35.94 oranında ve tavuk izolatlarında ise %13.92 oranında olmak üzere en sık rastlanan ÇİD paternleri sırasıyla B/DA/E/RD ve N/B/CT/E/SP/P/RD/DO/OT/TE olarak bulundu. Salmonella izolatlarında karşılaşılan bu yüksek dirençlilik oranlarının ve ÇİD paternlerinin insanlardaki Salmonella infeksiyonlarının tedavisinde risk oluşturabileceği belirtildi

The necessity of identity assessment of animal intestinal cell lines: A case report.

Eight intestinal cell lines, established from different animal species were submitted to DSMZ (German Collection of Microorganisms and Cell Cultures) in order to analyze their species of origin and their microbial contamination. Species identity was determined by PCR targeting mitochondrial genes and hence confirmed by sequencing the amplified PCR products. For three cell lines (CIEB, CLAB, PSI-1) we confirmed the species identity, whereas the species of origin of the three other cell lines (B6, B10XI and IPEC) was not the expected one: B6 and B10XI cells, which were supposed to be of chicken origin were identified as porcine cells. IPEC, allegedly a sub clone of the well-known porcine intestinal cell line IPEC-J2, was of bovine instead of porcine origin. However, two further IPEC-clones, namely IPEC-1 and IPEC-J2, provided by another source were shown to be derived from the correct species (i.e. pig). Furthermore, six out of these eight cell lines turned out to be highly contaminated with mycoplasma. Alerted by this high incidence of infected and false specified cell lines, we feel obliged to inform all those working with animal intestinal cell lines and we strongly recommend verifying the species identity before using them. Also, the presence of mycoplasma should be tested when taking the cells in culture for the first time, and this mycoplasma control should be repeated at regular time intervals (e.g. every 4weeks).

Diversity and origin of South African chickens

The objectives of this study were to analyze the genetic diversity and structure of South African conserved and field chicken populations and to investigate the maternal lineages of these chicken populations. Four South African conserved chicken populations (n = 89), namely, Venda (VD_C), Ovambo, Naked Neck, and Potchefstroom Koekoek from the Animal Production Institute of the Agricultural Research Council, and 2 field populations, the Venda and Ovambo (OV_F), from which the Ovambo and the Venda conservation flocks were assumed to have been sampled, were genotyped for 460 bp of the mitochondrial DNA (mtDNA) D-loop sequence. Haplotypes of these chickens were aligned to 7 Japanese and 9 Chinese and Eurasian chicken mtDNA D-loop sequences taken from GenBank and reflecting populations from presumed centers of domestication. Sequence analysis revealed 48 polymorphic sites that defined 13 haplotypes in the South African chicken populations. All 6 South African conserved and field chicken populations observed were found to be polymorphic, with the number of haplotypes ranging from 3 for VD_C to 8 for OV_F. The lowest haplotype diversity, 0.54 ± 0.08, was observed in VD_C chickens, whereas the highest value, 0.88 ± 0.05, was observed in OV_F chickens. Genetic diversity between the 4 South African conserved and 2 field chicken populations constituted 12.34% of the total genetic variation, whereas within-population diversity constituted 87.66% of the total variation. The median network analysis of the mtDNA D-loop haplotypes observed in the South African conserved and field populations and the reference set resulted in 5 main clades. All 6 South African chickens were equally represented in the major clade, E, which is presumed to be of Indian subcontinent maternal origin and may have its roots in Southeast Asia. The results showed multiple maternal lineages of South African chickens. Conservation flocks and field chicken populations shared the major haplotypes A, D and E, which were presumed to be of Chinese, Southeast Asian, and Indian subcontinental origin.

Methicillin-ResistantStaphylococcus aureusin Retail Meat, Detroit, Michigan, USA

Methicillin-Resistant<i>Staphylococcus aureus</i>in Retail Meat, Detroit, Michigan, USA

Multiple Maternal Lineages of Vietnamese Local Chickens Inferred by Mitochondrial DNA D-loop Sequences

Mitochondrial DNA (mtDNA) is considered a powerful source of molecular information to track the ancestry of breeds back hundreds of generations (Harpending et al., 1998). Different hypotheses about chicken domestication based on mtDNA analyses are found in the literature. Fumihito et al. (1996) suggested a monophyletic origin of domestic chickens from Gallus gallus gallus and that a single domestication event occurred in Thailand and adjacent regions, while Kanginakudru et al. (2008) found evidence for domestication of Indian chickens from Gallus gallus spadiceus and Gallus gallus gallus as well as from Gallus gallus murghi. A study that analyzed BCDO2, a gene encoding an enzyme which converts carotene into its colourless variant, suggested the introgression of the yellow skin gene from Gallus sonneratii into modern chicken breeds (Eriksson et al., 2008). Other reports assumed multiple and independent domestication events in South China, Southeast Asia and the Indian subcontinent (Liu et al., 2006 a; Oka et al., 2007). Liu et al. (2006) revealed nine divergent clades (named clades A-I) related to geographical distribution in a wide range of domestic chickens in Eurasian regions. Oka et al. (2007) identified seven clades (named clades A-G) in Japanese chickens of which the four clades A, B, C and E are identical to clades E, A, D and B, respectively, described by Liu et al. (2006).

Comparison of genotypes and antibiotic resistance of Campylobacter jejuni isolated from humans and slaughtered chickens in Switzerland

To get an overview of genotypes and antibiotic resistances in Swiss Campylobacter jejuni implicated in human gastroenteritis and to examine the association with isolates from chickens. Multilocus sequence typing (MLST) and flaB typing were applied to 136 human clinical isolates. Phenotypic resistance to 12 antimicrobials and genotypic resistance to macrolides and quinolones were determined. MLST resulted in 35 known and six new sequence types (ST). The flaB analysis revealed 35 different types, which - in combination with MLST - increased the resolution of the typing approach. Resistance to quinolones, tetracycline and ampicillin was found in 37·5, 33·1 and 8·1% of the isolates, respectively, whereas macrolide resistance was found only once. Genotypic and phenotypic resistance correlated in all cases. A comparison to Camp. jejuni isolated from slaughtered chickens was performed. While 86% of the quinolone-sensitive human isolates showed overlapping MLST-flaB types with those of chicken origin, resistant strains showed only 39% of matching types. Mainly quinolone-sensitive Camp. jejuni strains implicated in human campylobacteriosis showed matching genotypes with isolates originating from chickens. A large proportion of human cases in Switzerland are likely to originate from domestic chickens, confirming that prevention measures in the poultry production are important.

Genetic diversity and genealogical origins of domestic chicken

This paper reviews some important features of the chicken genome, genealogical origins and the current status of the genetic diversity of the chicken. The small chicken genome exhibits six times more single nucleotide polymorphisms (>7,000,000 SNPs) than mammalian genomes and considerable microsatellite content (375,000). An obvious debate is still dedicated to whether chicken origin is monophyletic or polyphyletic. Modern genetic analysis conducted across the world's chicken population has determined no restricted phylo-geographical centre of domestication, as has been shown for other livestock species. Wild, unselected native and some fancy and conserved chicken populations showed high microsatellite and SNP diversity. Within-population diversity was higher than between-population diversity in selected or inbred chicken populations, whereas village chickens almost showed no sub-division in clusters. There is a variable degree of mitochondrial-DNA control-region (mtDNA-CR) sequence diversity within native chicken populations. Although commercial broilers exhibited considerable diversity in all marker types, they have lost >50% of SNP alleles found in their ancestors. Moreover, the linkage disequilibrium (LD) within broiler lines extends over shorter distances than in other inbred livestock populations. Domestic chickens are still genetically diverse and further conservation efforts are warranted to maintain the large between-population diversity.

Temperature-dependent phenotypic variation of Campylobacter jejuni lipooligosaccharides

BackgroundCampylobacter jejuni is a major bacterial cause of food-borne enteritis, and its lipooligosaccharide (LOS) plays an initiating role in the development of the autoimmune neuropathy, Guillain-Barré syndrome, by induction of anti-neural cross-reactive antibodies through ganglioside molecular mimicry.ResultsHerein we describe the existence and heterogeneity of multiple LOS forms in C. jejuni strains of human and chicken origin grown at 37°C and 42°C, respectively, as determined on sodium dodecyl sulphate-polyacrylamide electrophoresis gels with carbohydrate-specific silver staining and blotting with anti-ganglioside ligands, and confirmed by nuclear magnetic resonance (NMR) spectroscopy. The C. jejuni NCTC 11168 original isolate (11168-O) was compared to its genome-sequenced variant (11168-GS), and both were found to have a lower-Mr LOS form, which was different in size and structure to the previously characterized higher-Mr form bearing GM1 mimicry. The lower-Mr form production was found to be dependent on the growth temperature as the production of this form increased from ~5%, observed at 37°C to ~35% at 42°C. The structure of the lower-Mr form contained a β-D-Gal-(1→3)-β-D-GalNAc disaccharide moiety which is consistent with the termini of the GM1, asialo-GM1, GD1, GT1 and GQ1 gangliosides, however, it did not display GM1 mimicry as assessed in blotting studies but was shown in NMR to resemble asialo-GM1. The production of multiple LOS forms and lack of GM1 mimicry was not a result of phase variation in the genes tested of NCTC 11168 and was also observed in most of the human and chicken isolates of C. jejuni tested.ConclusionThe presence of differing amounts of LOS forms at 37 and 42°C, and the variety of forms observed in different strains, indicate that LOS form variation may play a role in an adaptive mechanism or a stress response of the bacterium during the colonization of different hosts.

Prudent use of antimicrobial agents: Not just for humans

The use of antimicrobial agents (AA) is required for the treatment of infectious diseases, but, at the same time, is the main cause for the selection of antimicrobial resistant bacteria. The wide use of AA in human medicine is a key cause of this problem, but not the only one, as other ‘‘non-human’’ uses of AA are also contributing to the alarming increase of resistant bacteria. AA are used in animals for therapeutic and prophylactic purposes in order to cure and prevent bacterial diseases. In these cases, AA are administered under veterinary control. Another use of AA in animals, although banned since 2006 in the European Union (EU) but still allowed in other non-European countries (USA, Japan, Australia, among others), is as animal growth promoters (AGP). In this case, AA are added in sub-therapeutic doses and for long periods of time in the feed of healthy animals, conditions that could contribute to the selection of resistant bacteria. The use of AA as AGP has been the object of strong debate in the scientific community for its potential risk to human health. AA use as AGP is associated to the selection of resistant intestinal bacteria in animals (both zoonotics and commensals), that could be transferred to humans through the food chain; these selected bacteria could also transfer resistant genes to other human intestinal bacteria. 1,2 There are different regulations for AGP use in those countries where they are still allowed. 3 The use of avoparcin as AGP in the EU, a glycopeptide with a similar structure to vancomycin, is a clear example of the contribution of this use in the selection and dissemination of vancomycinresistant enterococci in the animal ecosystem, with its potential risk to human health. After the EU banning of avoparcin as AGP in 1997, the prevalence of these resistant bacteria in intestinal samples of animals and healthy humans and in foods has significantly decreased. 2 The use of AA to treat or to prevent infectious diseases in food producing animals (FPA) also contribute to the selection of resistant bacteria that can be transferred from animals to humans. The food chain is considered as a transmission vehicle of resistant bacteria to humans, although direct animal-human contact can be another transmission route. Some examples will be highlighted. The introduction of fluoroquinolones (FQ) in animal production was associated with an increase of FQ-resistant bacteria isolated from FPA (as Campylobacter or E. coli, among others) and, later, in zoonotic bacteria implicated in human infections. 2,4 However, in Australia, where FQ are not used in FPA, this association has not been observed. FQ use in poultry was banned in Denmark in 2003, and was followed by a decrease in the percentage of FQ-resistant Campylobacter coli isolates of chicken origin. Similarly, the US Food and Drug Administration (FDA) banned the use of enrofloxacin in poultry in 2005 due to its possible risk to human health. 2

Campylobacter jejuni induces an anti-inflammatory response in human intestinal epithelial cells through activation of phosphatidylinositol 3-kinase/Akt pathway

Campylobacter jejuni ( C. jejuni) is the most common cause of human acute bacterial gastroenteritis. Poultry is a major reservoir of C. jejuni and considered an important source of human infections, thus, it is important to understand the host response to C. jejuni from chicken origin. In this study, we demonstrated firstly that a chicken isolate SC11 colonized chicks faster than clinical isolate NCTC11168. Using the SC11, we further studied the host responds to C. jejuni in terms of inflammatory response and involvement of cellular signaling pathways. Infection of C. jejuni SC11 was able to activate phosphatidylinositol 3-kinase (PI3K)/Akt pathway and induce pro-inflammatory interleukin-8 (IL-8) as well as anti-inflammatory cytokine IL-10 in human intestinal epithelial cell line Colo 205. The signalling pathways PI3K/Akt and mitogen-activated protein (MAP) kinases ERK and p38 were involved in C. jejuni-induced IL-8 and IL-10 expression. Inhibition of PI3K resulted in augmentation of C. jejuni-induced IL-8 production, concomitant with down-regulation of IL-10 mRNA, indicating an anti-inflammatory response was activated and associated with the activation of P13K/Akt. Similar effect was observed for cytolethal distending toxin (CDT) deficient mutants. Moreover, we demonstrated that heat-killed bacteria were able to induce IL-8 and IL-10 expression to a lower level than live bacteria. We therefore conclude that C. jejuni activate a PI3K/Akt-dependent anti-inflammatory pathway in human intestinal epithelial cells which may benefit the intracellular survival of C. jejuni during infection.

Differential Sensitivity of Well-Differentiated Avian Respiratory Epithelial Cells to Infection by Different Strains of Infectious Bronchitis Virus

Infectious bronchitis virus (IBV) is an avian coronavirus affecting the respiratory tract of chickens. To analyze IBV infection of the lower respiratory tract, we applied a technique that uses precision-cut lung slices (PCLSs). This method allows infection of bronchial cells within their natural tissue composition under in vitro conditions. We demonstrate that IBV strains 4/91, Italy02, and QX infect ciliated and mucus-producing cells of the bronchial epithelium, whereas cells of the parabronchial tissue are resistant to infection. This is the first study, using PCLSs of chicken origin, to analyze virus infection. PCLSs should also be a valuable tool for investigation of other respiratory pathogens, such as avian influenza viruses.

Transfer of vanA from an Enterococcus faecium isolate of chicken origin to a CC17 E. faecium isolate in the intestine of cephalosporin-treated mice

Transfer of vanA from an Enterococcus faecium isolate of chicken origin to a CC17 E. faecium isolate in the intestine of cephalosporin-treated mice

The origin and genetic variation of domestic chickens with special reference to junglefowls Gallus g. gallus and G. varius.

It is postulated that chickens (Gallus gallus domesticus) became domesticated from wild junglefowls in Southeast Asia nearly 10,000 years ago. Based on 19 individual samples covering various chicken breeds, red junglefowl (G. g. gallus), and green junglefowl (G. varius), we address the origin of domestic chickens, the relative roles of ancestral polymorphisms and introgression, and the effects of artificial selection on the domestic chicken genome. DNA sequences from 30 introns at 25 nuclear loci are determined for both diploid chromosomes from a majority of samples. The phylogenetic analysis shows that the DNA sequences of chickens, red and green junglefowls formed reciprocally monophyletic clusters. The Markov chain Monte Carlo simulation further reveals that domestic chickens diverged from red junglefowl 58,000±16,000 years ago, well before the archeological dating of domestication, and that their common ancestor in turn diverged from green junglefowl 3.6 million years ago. Several shared haplotypes nonetheless found between green junglefowl and chickens are attributed to recent unidirectional introgression of chickens into green junglefowl. Shared haplotypes are more frequently found between red junglefowl and chickens, which are attributed to both introgression and ancestral polymorphisms. Within each chicken breed, there is an excess of homozygosity, but there is no significant reduction in the nucleotide diversity. Phenotypic modifications of chicken breeds as a result of artificial selection appear to stem from ancestral polymorphisms at a limited number of genetic loci.

Lack of Phylogeographic Structure in Nigerian Village Chickens Revealed by Mitochondrial DNA D-loop Sequence Analysis

4 Abstract: Genetic diversity studies that utilize phenotypic and genetic information are informative when formulating breeding and conservation plans. The present study utilizes sequences of mitochondrial DNA (mtDNA) D-loop region of 232 village chickens from Southern and Northern Nigeria to determine the origin and diversity of Nigerian local chickens. Thirty-six polymorphic sites which generate 35 haplotypes are identified. Phylogenetic analyses group Nigerian local chickens to a single clade and 97.8% of the total maternal variation occurs within populations. Reference sequences representing the major chicken mtDNA lineages from Asia indicate the Indian subcontinent to be the likely main center of origin of Nigerian village chicken. Lack of phylogeograph ic structure among Nigerian village chickens suggest extensive genetic intermixing within the country.

The plumage colour Dark brown in chicken is caused by an 8 kb deletion upstream of SOX10

Domestic animals have been selected by humans for thousands of years, which have drastically altered their genetic constitution and phenotypes. In this thesis, several of the most important genes causing pigmentation differences between the wild red junglefowl (Gallus gallus) and domestic chickens have been identified. Pigmentation phenotypes are easily scored, and the genes underlying these phenotypes are valuable models to study gene function and gene interaction. Dominant white colour is widespread among domestic chickens. The Dominant white allele specifically inhibits the expression of black (eumelanin) pigment and we identified several insertion/deletion mutations in the PMEL17 gene causing the different phenotypes controlled by this locus. The Silver allele on the other hand inhibits the expression of red (pheomelanin) colour and is a genetic variant of the SLC45A2 gene. Silver is the first pheomelanin-specific mutation(s) reported for this gene. An 8 kb deletion, including a conserved enhancer element, 14 kb upstream of the transcription factor SOX10 is causing the Dark brown phenotype. This phenotype restricts the expression of eumelanin and enhances red pheomelanin in specific parts of the plumage. These three gene identifications have extended the knowledge about genes affecting melanocyte function. Carotenoid-based pigmentation is of utmost importance in birds and other animals. The yellow skin allele in chicken allows deposition of carotenoids in skin and explains why most domestic chickens have yellow legs. We demonstrated that the yellow skin phenotype is caused by a tissue specific regulatory mutation in the gene for the enzyme beta-caroten dioxygenase 2 (BCDO2). This was the first identification of a specific gene underlying carotenoid-based pigmentation. Interestingly, the yellow skin haplotype was shown to originate from the grey junglefowl (Gallus sonneratii) and not the red junglefowl as expected, thus presenting the first conclusive evidence for a hybrid origin of the domestic chicken.

Antigenic variation between Newcastle disease viruses of goose and chicken origin

Newcastle disease virus (NDV) is believed to infect only domestic avian species, with waterfowl such as geese either not being infected, even by virulent strains, or developing only inapparent infection. Since the late 1990s, a new infectious disease producing high morbidity and mortality among geese broke out in many provinces of China. This disease was caused by a serotype I avian paramyxovirus known as (APMV-1)-NDV. To investigate how NDV spreads between chickens and geese, the serological similarities of NDV strains (goose-origin NDV/NA-1 and chicken-origin NDV/F48E9, F48E8) were assessed by cross-neutralization assays both in vivo and in vitro. The results indicated that antigenic variation had occurred between NDV/NA-1 strains and NDV/F48E9, F48E8 strains. Notably, NDV/NA-1 effectively protected vaccinated birds from morbidity and mortality against NDV/NA-1 strain challenge and significantly reduced virus shedding from the vaccinated birds when compared with F48E9-vaccinated birds. This might provide clues to the evolution of the goose NDV.

Characterization of antimicrobial resistance and molecular determinants of beta-lactamase in Escherichia coli isolated from chickens in China during 1970–2007

The aim of this study is to investigate the trend of antimicrobial resistance of 696 Escherichia coli strains of chicken origin in China during 1970–2007, and to characterize the beta-lactamase determinants of these strains. Minimum inhibitory concentrations (MICs) of these strains against 11 antimicrobials were determined by the broth microdilution method. Quinolone-resistant, and first-generation cephalosporin-resistant strains have emerged since the 1990s; third-generation cephalosporin-resistant strains were not detected until 2003. Afterwards these resistant strains increased rapidly, and an obvious increase of isolates with decreased susceptibility to forfenicol was also observed. Three classes of beta-lactamase genes in E. coli strains were detected by PCR and confirmed by DNA sequencing. The detection rate of narrow-spectrum beta-lactamase genes decreased from 71.2% in the 1970s to 28.8% during 2004–2007. Extended-spectrum beta-lactamase (ESBL) genes did not emerge until 2004 and the detection rate was 18.5% between 2004 and 2007. The detection rate of bla CMY-2, which emerged between 2000 and 2003, climbed to 6.6% during 2004–2007. bla CTX-M was the dominant genotype (75%) in ESBL gene-harboring E. coli strains. Fifty strains (17.6%), co-harboring multiple kinds of beta-lactamase genes, were detected in 284 beta-lactamase-producing strains. Southern hybridization revealed that two- or three kinds of ESBL and/or CMY-2 genes co-located on one plasmid in 9 strains. The rising trend of antimicrobial resistance and the high prevalence of beta-lactamase determinants in E. coli strains of chicken origin might be attributed to overuse of antimicrobials, especially beta-lactams, in poultry production.

HIGH PREVALENCE OF EXTENDED‐SPECTRUM β‐LACTAMASES ESCHERICHIA COLI AND VANCOMYCIN‐RESISTANT ENTEROCOCCI ISOLATES FROM CHICKEN PRODUCTS. A PROBLEM OF PUBLIC HEALTH

ABSTRACT Twenty‐nine chicken products were acquired from different supermarkets in Portugal during September to December 2007 and were analyzed for extended‐spectrum β‐lactamases (ESBL) Escherichia coli and vancomycin‐resistant enterococci (VRE). Cefotaxime‐resistant E. coli isolates were recovered in 27 of 29 chicken samples representing 93% of the analyzed samples. The highest percentages of resistance (more than 50% of the isolates) were detected for ampicillin, nalidixic acid and tetracycline. VRE isolates were detected in 17 of 29 samples of chicken origin (59%) and were identified as Enterococcus durans (n = 15) and E. faecium (n = 2) with the highest percentages of resistance being detected for erythromycin, tetracycline, ampicillin and ciprofloxacin. Seven E. durans and the two E. faecium isolates recovered from chicken wings, gizzard and skin show gelatinase activity. The high rate of colonization of chicken products by these bacteria supports other studies suggesting that the food chain could be a source of ESBL and VRE colonization in humans representing a public health problem. PRACTICAL APPLICATIONSThe data indicate that chicken products may be contaminated with a high prevalence of extended‐spectrum β‐lactamases Escherichia coli and vancomycin‐resistant enterococci (VRE). It is important to mention that the isolates present a diversity of phenotypes of antimicrobial resistance, and half of the VRE isolates show also gelatinase activity, indicating that these animals may be a reservoir of bacteria showing virulence and increased resistance to antimicrobial agents, raising special concerns about their transmission to humans through the food chain.

Collagen-induced arthritis in common marmosets: a new nonhuman primate model for chronic arthritis

IntroductionThere is an ever-increasing need for animal models to evaluate efficacy and safety of new therapeutics in the field of rheumatoid arthritis (RA). Particularly for the early preclinical evaluation of human-specific biologicals targeting the progressive phase of the disease, there is a need for relevant animal models. In response to this requirement we set out to develop a model of collagen-induced arthritis (CIA) in a small-sized nonhuman primate species (300 to 400 g at adult age); that is, the common marmoset (Callithrix jacchus).MethodsTwenty-two animals divided into three experiments were immunized with collagen type II (CII) of either bovine or chicken origin with different immunization strategies. The animals were analyzed for clinical manifestation of arthritis, hematology and clinical chemistry, immunological responses against CII and histopathological features of the arthritis.ResultsClinically manifest arthritis was observed in almost 100% (21 out of 22) of the animals. Fifty percent of the animals developed semi-acute CIA while the other 50% displayed a more chronic disease. Both cellular (CD3/CD4 and CD3/CD8) and humoral responses (IgM and IgG) against CII were involved in the development of the disease. Besides mild histopathological changes in bone and cartilage, severe inflammation in extraarticular tissues like periosteum and subcutaneous tissues was observed.ConclusionsThis new model in marmosets more closely resembles chronic RA with respect to the chronic disease course and pathomorphological presentation than the more acute monophasic and destructive CIA model in macaques. This model can therefore fill a niche in preclinical testing of new human specific therapeutics.