Large-scale genome analysis of bovine commensal Escherichia coli reveals that bovine-adapted E. coli lineages are serving as evolutionary sources of the emergence of human intestinal pathogenic strains.

How pathogens evolve their virulence to humans in nature is a scientific issue of great medical and biological importance. Shiga toxin (Stx)-producing Escherichia coli (STEC) and enteropathogenic E. coli (EPEC) are the major foodborne pathogens that can cause hemolytic uremic syndrome and infantile diarrhea, respectively. The locus of enterocyte effacement (LEE)-encoded type 3 secretion system (T3SS) is the major virulence determinant of EPEC and is also possessed by major STEC lineages. Cattle are thought to be the primary reservoir of STEC and EPEC. However, genome sequences of bovine commensal E. coli are limited, and the emerging process of STEC and EPEC is largely unknown. Here, we performed a large-scale genomic comparison of bovine commensal E. coli with human commensal and clinical strains, including EPEC and STEC, at a global level. The analyses identified two distinct lineages, in which bovine and human commensal strains are enriched, respectively, and revealed that STEC and EPEC strains have emerged in multiple sublineages of the bovine-associated lineage. In addition to the bovine-associated lineage-specific genes, including fimbriae, capsule, and nutrition utilization genes, specific virulence gene communities have been accumulated in stx- and LEE-positive strains, respectively, with notable overlaps of community members. Functional associations of these genes probably confer benefits to these E. coli strains in inhabiting and/or adapting to the bovine intestinal environment and drive their evolution to highly virulent human pathogens under the bovine-adapted genetic background. Our data highlight the importance of large-scale genome sequencing of animal strains in the studies of zoonotic pathogens.

Enteropathogenic Escherichia coli O80:H2 in Young Calves with Diarrhea, Belgium.

Serogroup O80 was detected in 40% of 104 enteropathogenic Escherichia coli isolates from calves with diarrhea from 42 farms in Belgium during 2008‒2015. These isolates harbored the eae-ξ and fliCH2 genes, similar to the O80 attaching-effacing Shigatoxigenic E. coli isolates found in humans in France. This strain might be emerging.

Zoonoses in pet birds: review and perspectives.

Pet birds are a not-so-well known veterinarian's clientship fraction. Bought individually or in couples, as families often do (which is a lucrative business for pet shops or local breeders) or traded (sometimes illegally) for their very high genetic or exotic value, these birds, commonly canaries, parakeets or parrots, are regularly sold at high prices. These animals, however, are potential carriers and/or transmitters of zoonotic diseases. Some of them could have an important impact on human health, like chlamydophilosis, salmonellosis or even highly pathogenic avian influenza A H5N1. This review paper, although non exhaustive, aims at enlightening, by the description of several cases of bird-human transmission, the risks encountered by bird owners, including children. Public health consequences will be discussed and emphasis will be made on some vector-borne diseases, known to be emergent or which are underestimated, like those transmitted by the red mite Dermanyssus gallinae. Finally, biosecurity and hygiene, as well as prevention guidelines will be developed and perspectives proposed.

Characterization of methicillin-resistant Staphylococcus pseudintermedius isolated from dogs and cats.

The aim of this study was to explore the presence of methicillin-resistant Staphylococcus pseudintermedius (MRSP) in a collection of S. pseudintermedius strains isolated from dogs and cats with dermatitis in Japan and to compare their genotypic and phenotypic characteristics. Clonal relationships were determined by pulse field gel electrophoresis (PFGE), staphylococcal chromosomal cassette mec (SCCmec) typing, and multilocus sequence typing (MLST). Biofilm formation assay was performed using safranin staining in microplates. Three virulence genes coding for S. intermedius exfoliative toxin and Panton-Valentine leukocidin (siet, lukS-PV and lukF-PV) were searched for in a collection of strains. Antimicrobial resistance against 15 antibiotics was studied by a disc diffusion method. Twenty-seven MRSP were isolated. According to PFGE results the isolates were not closely related except for a few strains. MLST showed that the strains belonged to five groups, ST71 and ST26 being the two most prevalent. Three types of SCCmec (II, II-III and V) were identified. All isolates were siet-positive but PVL-negative. Most strains (except for two) produced strong biofilm in tryptic soy broth with glucose. Seventy-eight percent of the isolates were resistant or intermediate to twelve or more antibiotics. Our study demonstrates that the ST71 lineage is widespread in Japan and that ST26 could represent an emerging lineage. Moreover, most of our strains are capable of forming strong biofilm and possess siet gene, two virulence characteristics that probably help the bacteria to persist and spread. Finally, our MRSP strains show a strong resistance profile to antibiotics commonly used in veterinary medicine.

Identification and typing of Salmonella enterica serotypes isolated from guinea fowl (Numida meleagris) farms in Benin during four laying seasons (2007 to 2010).

The main problem for the local guinea fowl (Numida meleagris) traditional farming and raising system in north-east Benin is the high mortality rate of the keets (up to 70%) due to a combination of climatic, nutritional, hygienic and infectious causes. The present study was carried out to identify and compare the isolates of Salmonella enterica from necropsied keets, laying guinea fowl, surrogate hen mothers, other contact animal species and farmers during four laying seasons (2007 to 2010). S. enterica belonging to eight different serotypes (Adelaide, Farakan, Kingston, Legon, Luke, Oakland, Sangalkam and Teshie) and one untypable isolate were isolated from 13 to 19% of the necropsied keets. The serotypes Adelaide, Farakan, Luke, Sangalkam and Teshie and the untypable isolate were isolated in only one township during 1 year of sampling, while serotypes Oakland, Legon and Kingston were present in two to three townships for 2 to 3 years of sampling. Serotypes Farakan, Kingston, Legon, Oakland and Sangalkam were also isolated from faecal samples of laying guinea fowl and/or surrogate domestic fowl hen mothers. Further comparison by pulsed-field gel electrophoresis and virulotyping provided evidence for their clonality within each of those five serotypes and therefore for the adult guinea fowl and/or hens as the most probable origin of contamination of the keets. The antibiotic resistance profiles, with all isolates resistant to oxacillin, sulfamethoxazol and colistin, emphasize the rise of antibiotic resistance in salmonellas from guinea fowl in this area and the need for alternative therapy policies for these birds.

Escherichia coli O80 in Healthy Cattle: Absence of Shigatoxigenic and Enteropathogenic E. coli O80:H2 and (Phylo) Genomics of Non-Clonal Complex 165 E. coli O80.

The origin of human and calf infections by Shigatoxigenic (STEC) and enteropathogenic (EPEC) Escherichia coli O80:H2 is still unknown. The aim of this study was to identify E. coli O80 in healthy cattle with an emphasis on melibiose non-fermenting E. coli O80:H2. Faecal materials collected from 149 bulls at 1 slaughterhouse and 194 cows on 9 farms were tested with O80 antigen-encoding gene PCR after overnight growth in enrichment broths. The 53 O80 PCR-positive broths were streaked on different (semi-)selective agar plates. Five E. coli colonies from 3 bulls and 11 from 2 cows tested positive with the O80 PCR, but no melibiose non-fermenting E. coli was isolated. However, these 16 E. coli O80 were negative with PCR targeting the fliCH2, eae, stx1, stx2 and hlyF genes and were identified by WGS to serotypes and sequence types O80:H6/ST8619 and O80:H45/ST4175. They were phylogenetically related to E. coli O80:H6 and O80:H45 isolated from different animal species in different countries, respectively, but neither to STEC and EPEC O80:H2/ST301, nor to other serotypes of the clonal complex 165. As a conclusion, healthy adult cattle were not identified as a source of contamination of humans and calves by STEC or EPEC O80:H2.

Virulence of Shigatoxigenic and Enteropathogenic Escherichia coli O80:H2 in Galleria mellonella Larvae: Comparison of the Roles of the pS88 Plasmids and STX2d Phage.

The invasiveness properties of Shigatoxigenic and enteropathogenic Escherichia coli (STEC and EPEC) O80:H2 in humans and calves are encoded by genes located on a pS88-like ColV conjugative plasmid. The main objectives of this study in larvae of the Galleria mellonella moth were therefore to compare the virulence of eight bovine STEC and EPEC O80:H2, of two E. coli pS88 plasmid transconjugant and STX2d phage transductant K12 DH10B, of four E. coli O80:non-H2, and of the laboratory E. coli K12 DH10B strains. Thirty larvae per strain were inoculated in the last proleg with 10 µL of tenfold dilutions of each bacterial culture corresponding to 10 to 106 colony-forming units (CFUs). The larvae were kept at 37 °C and their mortality rate was followed daily for four days. The main results were that: (i) not only the STEC and EPEC O80:H2, but also different E. coli O80:non-H2 were lethal for the larvae at high concentrations (from 104 to 106 CFU) with some variation according to the strain; (ii) the Stx2d toxin and partially the pS88 plasmid were responsible for the lethality caused by the E. coli O80:H2; (iii) the virulence factors of E. coli O80:non-H2 were not identified. The general conclusions are that, although the Galleria mellonella larvae represent a useful first-line model to study the virulence of bacterial pathogens, they are more limited in identifying their actual virulence properties.

Clinical significance of Escherichia albertii.

Discriminating Escherichia albertii from other Enterobacteriaceae is difficult. Systematic analyses showed that E. albertii represents a substantial portion of strains currently identified as eae-positive Escherichia coli and includes Shiga toxin 2f-producing strains. Because E. albertii possesses the eae gene, many strains might have been misidentified as enterohemorrhagic or enteropathogenic E. coli.

Development of a duplex qPCR for the differentiation of a live attenuated Escherichia coli aroA mutant vaccine strain from field isolates in chickens.

Avian pathogenic Escherichia coli (APEC) can cause colibacillosis in poultry, characterised by localised or systemic infections. Colibacillosis is considered one of the leading causes of economic losses in the poultry industry due to reduced performance, increased mortality, treatment costs and carcass condemnations. A live attenuated Escherichia coli O78 aroA gene mutant is widely used to prevent disease. However, no effective strategies to differentiate the vaccine strain from field strains are available, hampering follow-up of vaccination campaigns. In the current study, we report a PCR-based method to simultaneously detect the vaccine strain by targeting the vaccine-specific mutation in the aroA gene, as well as the wild type E. coli strains by targeting the xanQ gene. The specificity of this PCR was evaluated using 123 E. coli isolates, form which 5 WT aroA auxotrophic strains (WT strains with a natural aroA deficiency), as well as 7 non-Escherichia isolates. The PCR showed 100% sensitivity of the xanQ primers for E. coli detection and 100% sensitivity of the ΔaroA primers for the vaccine strain. In order to allow quantification of the vaccine strain in complex samples containing many different E. coli strains and other related organisms, such as chicken faeces, a probe-based duplex qPCR was developed. The limit of detection (LOD) of this duplex qPCR method was 8.4*103 copies/g faeces. The specificity of the duplex qPCR was confirmed by determining both the vaccine strain levels, and the total E. coli load in intestinal digesta from both vaccinated and non-vaccinated birds. E. coli could be detected in both vaccinated and non-vaccinated birds. The duplex qPCR was specific for the vaccine strain as this strain was detected in all vaccinated birds, whereas no signal was detected in non-vaccinated birds. The duplex qPCR is helpful in monitoring colonization and shedding of the vaccine strain.

Study of polymorphisms in tir, eae and tccP2 genes in enterohaemorrhagic and enteropathogenic Escherichia coli of serogroup O26.

BACKGROUND: Enteropathogenic (EPEC) and enterohaemorrhagic (EHEC) Escherichia coli are responsible for food poisoning (enteritis and enterotoxaemia) in humans in developed countries. Cattle are considered to be an important reservoir of EHEC and EPEC strains for humans. Moreover, some of the strains, belonging to the O26, O111, O118 serogroups, for example, are also responsible for digestive disorders in calves. The Translocated intimin receptor (Tir), the intimin (Eae) and the Tir-cytoskeleton coupling protein (TccP) represent three virulence factors implicated in the intimate attachment of the bacteria to the eukaryotic cell. Major variants have already been described for these genes among the different serogroups but minor variations have not often been studied. In this study, we examined the polymorphisms of the tir, eae and tccP2 genes of O26 strains (EPEC and EHEC isolated from bovines and from humans) with the aim to determine whether these polymorphisms are host specific or not. RESULTS: Of the 70 tested strains, 10 strains (14% of the strains) presented one or several polymorphisms in the tir and eae genes, which have never previously been described. Concerning tccP2 detection, 47 of the 70 strains (67% of the strains) were found to be positive for this gene. Most of the strains were found to possess tccP2 variants described in strains of serogroup O26. Nevertheless, three strains had tccP2 genes respectively described in strains of serogroup O111, O103 and O55. Moreover, none of the polymorphisms was statistically specific to the bovine or the human isolates. Nevertheless, the two major variants of tccP2 were statistically associated with the pathotype (EPEC or EHEC). CONCLUSIONS: In conclusion, tir and eae gene polymorphisms were found not to be numerous and not to be predominantly synonymous. Moreover, no difference was observed between human and bovine strains regarding the presence of polymorphisms. Finally, some tccP2 variants appeared to be pathotype specific. Further investigations need to be performed on a larger number of strains in order to confirm this specificity.

Genomic relatedness of a canine Lactococcus garvieae to human, animal and environmental isolates.

Lactococcus (L.) garvieae is a zoonotic fish pathogen that can also cause bacteraemia and endocarditis in humans and has been isolated from healthy or diseased domestic animals. Nevertheless L. garvieae is more an opportunistic, than a primary pathogen since most affected humans have predisposing conditions and comorbidities. L. garvieae is also present in other animal species, most frequently cattle, but also sheep, goats, water buffaloes, and pigs, and much more rarely dogs, cats, horses, camel, turtle, snake and crocodile. The purpose of this study was to genomically (i) confirm the identification by MALDI-TOF MS® of a L. garvieae from the nasal discharge of a dog with chronic respiratory disorders and (ii) compare this canine isolate with human and animal L. garvieae isolates. According to the BLAST analysis after Whole Genome Sequencing, this canine isolate was more than 99% identical to 3 L. garvieae and belonged to a new Multi-Locus Sequence Type (ST45). MLST and whole genomes-based phylogenetic analysis were performed on the canine isolate and the 40 genomes available in Genbank. The canine L. garvieae was most closely related to an Australian camel and an Indian fish L. garvieae and more distantly to human L. garvieae. Twenty-five of the 29 putative virulence-associated genes searched for were detected, but not the 16 capsule-encoding genes. The heterogeneity of the L. garvieae species is reflected by the diversity of the MLSTypes and virulotypes identified and by the phylogenetic analysis.

Whole Genome Sequencing of Staphylococci Isolated From Bovine Milk Samples.

Staphylococci are among the commonly isolated bacteria from intramammary infections in bovines, where Staphylococcus aureus is the most studied species. This species carries a variety of virulence genes, contributing to bacterial survival and spread. Less is known about non-aureus staphylococci (NAS) and their range of virulence genes and mechanisms, but they are the most frequently isolated bacteria from bovine milk. Staphylococci can also carry a range of antimicrobial resistance genes, complicating treatment of the infections they cause. We used Illumina sequencing to whole genome sequence 93 staphylococcal isolates selected from a collection of staphylococcal isolates; 45 S. aureus isolates and 48 NAS isolates from 16 different species, determining their content of antimicrobial resistance genes and virulence genes. Antimicrobial resistance genes were frequently observed in the NAS species as a group compared to S. aureus. However, the lincosamide resistance gene lnuA and penicillin resistance gene blaZ were frequently identified in NAS, as well as a small number of S. aureus. The erm genes conferring macrolide resistance were also identified in several NAS isolates and in a small number of S. aureus isolates. In most S. aureus isolates, no antimicrobial resistance genes were detected, but in five S. aureus isolates three to six resistance genes were identified and all five of these carried the mecA gene. Virulence genes were more frequently identified in S. aureus, which contained on average five times more virulence genes compared to NAS. Among the NAS species there were also differences in content of virulence genes, such as S. chromogenes with a higher average number of virulence genes. By determining the content of a large selection of virulence genes and antimicrobial resistance genes in S. aureus and 16 different NAS species our results contribute with knowledge regarding the genetic basis for virulence and antimicrobial resistance in bovine staphylococci, especially the less studied NAS. The results can create a broader basis for further research into the virulence mechanisms of this important group of bacteria in bovine intramammary infections.

Prevalence, molecular typing, and antibiotic sensitivity of enteropathogenic, enterohaemorrhagic, and verotoxigenic Escherichia coli isolated from veal calves.

Cattle are considered to be an important reservoir of enterohaemorrhagic Escherichia coli (EHEC) and verotoxigenic Escherichia coli (VTEC) strains that can cause disease in humans, and numerous studies of the prevalence of these strains in cattle (focusing mainly on dairy and beef cattle) have been carried out in different regions of Europe, Asia, and America. To date, only a few studies of veal calves have been published focusing on EHEC strains belonging to the O157 serogroup EHEC, whereas EHEC and VTEC can belong to hundreds of different serotypes (many of which are as dangerous to humans as the O157:H7 EHEC, such as strains of the O26, O91, O103, O111, O113 and O145 serogroups). The aim of this study was to investigate the presence of enteropathogenic Escherichia coli (EPEC), EHEC, and VTEC strains in veal calves in Belgium and to characterize the positive isolates (serogroups, virulence-associated factor-encoding genes and antibiotic resistance profiles). The prevalence of EPEC, EHEC, and VTEC strains in faecal samples from veal calves in Belgium was found to be 11.7% (6.5% of the calves were found to be positive for EPEC strains, 2.6% for EHEC, and 3.9% for VTEC strains). No O157:H7 EHEC Strain was identified, but three calves were found to carry strains belonging to the O26 and O111 serogroups. The results of antibiotic sensitivity tests showed a high level of resistance (83% of strains were resistant or intermediate resistant to five or more antibiotics of the 13 tested antibiotics), which might be caused by the frequent use of antibiotics in veterinary practice.

Harley William Moon (1936-2018).

Harley William Moon,DVM, Ph.D., an outstanding American person and researcher of comparative microbiology and pathology of intestinal diseases, the former director of the USDA, ARS, National Animal Disease Center (Iowa), of Plum Island Animal Disease Center (New York) and of Veterinary Research Institute of Iowa State University, member of the National Academy of Sciences (USA) passed away after some difficult and lonely last years of his life, on October 7, 2018 at the age of 82.

Putative adhesins of enteropathogenic and enterohemorrhagic Escherichia coli of serogroup O26 isolated from humans and cattle.

Enterohemorrhagic Escherichia coli (EHEC) strains are responsible for food poisoning in developed countries via consumption of vegetal and animal food sources contaminated by ruminant feces, and some strains (O26, O111, and O118 serogroups) are also responsible for diarrhea in young calves. The prevalence of 27 putative adhesins of EHEC and of bovine necrotoxigenic E. coli (NTEC) was studied with a collection of 43 bovine and 29 human enteropathogenic (EPEC) and EHEC strains and 5 non-EPEC/non-EHEC (1 bovine and 4 human) O26 strains, using specific PCRs. Four "groups" of adhesins exist, including adhesins present in all O26 strains, adhesins present in most O26 strains, adhesins present in a few O26 strains, and adhesins not present in O26 strains. The common profile of EHEC/EPEC strains was characterized by the presence of loc3, loc5, loc7, loc11, loc14, paa, efa1, iha, lpfA(O26), and lpfA(O113) genes and the absence of loc1, loc2, loc6, loc12, loc13, saa, and eibG genes. Except for the lpfA(O26) gene, which was marginally associated with bovine EHEC/EPEC strains in comparison with human strains (P = 0.012), none of the results significantly differentiated bovine strains from human strains. One adhesin gene (ldaE) was statistically (P < 0.01) associated with O26 EHEC/EPEC strains isolated from diarrheic calves in comparison with strains isolated from healthy calves. ldaE-positive strains could therefore represent a subgroup possessing the specific property of producing diarrhea in young calves. This is the first time that the distribution of putative adhesins has been described for such a large collection of EHEC/EPEC O26 strains isolated from both humans and cattle.

Assessment of two selective agar media to isolate colistin-resistant bovine Escherichia coli: Correlation with minimal inhibitory concentration and presence of mcr genes.

The identification of colistin-resistant enterobacteria in veterinary medicine is impaired by the absence of first-line reliable phenotypic assay. The purpose of this study was to assess two selective agar media for the detection of colistin-resistant bovine pathogenic Escherichia coli. A total of 158 E. coli (46 R , 96 I and 16 S at the disk diffusion assay) isolated between 2013 and 2018 from <3 month-old calves suffering enteritis or septicaemia, were (i) tested by the broth dilution assay to determine colistin Minimal Inhibitory Concentrations (MIC); (ii) streaked on CHROMID® Colistin_R and CHROMagar™ COL-APSE agar plates; (iii) submitted to a pentaplex PCR to identify the presence of mcr-1 to mcr-5 genes. Of the 92 E. coli growing on both agar media, 90 had a MIC > 2.0 µg/ml as had the 3 E. coli that grew only on the CHROMID® Colistin_R agar medium and one E. coli that grew on neither agar media. Therefore, the positive predictive values of the CHROMID® Colistin_R and CHROMagar™ COL-APSE agar media were both 0.98 whereas their negative predictive values were 0.98 and 0.94, respectively. Also noteworthy 43 of the 46 R isolates had a MIC > 2.0 µg/ml and grew on both selective media as did half of the 96 I isolates and only 1 of the S isolates. Conversely, only 30 of the 90 isolates that grew on both agar media and with a MIC > 2.0 µg/ml tested positive for the mcr-1 or mcr-2 genes with the pentaplex PCR. These two selective agar media can be used to reliably detect colistin-resistant E. coli. Positive growth was highly correlated with R results at the disk diffusion assay, but not with the presence of mcr genes.

New Bacteriophages against Emerging Lineages ST23 and ST258 of Klebsiella pneumoniae and Efficacy Assessment in Galleria mellonella Larvae.

Klebsiella pneumoniae is a bacterial pathogen of high public health importance. Its polysaccharide capsule is highly variable but only a few capsular types are associated with emerging pathogenic sublineages. The aim of this work is to isolate and characterize new lytic bacteriophages and assess their potential to control infections by the ST23 and ST258 K. pneumoniae sublineages using a Galleria mellonella larvae model. Three selected bacteriophages, targeting lineages ST258 (bacteriophages vB_KpnP_KL106-ULIP47 and vB_KpnP_KL106-ULIP54) and ST23 (bacteriophage vB_KpnP_K1-ULIP33), display specificity for capsular types KL106 and K1, respectively. These podoviruses belong to the Autographivirinae subfamily and their genomes are devoid of lysogeny or toxin-associated genes. In a G. mellonella larvae model, a mortality rate of 70% was observed upon infection by K. pneumoniae ST258 and ST23. This number was reduced to 20% upon treatment with bacteriophages at a multiplicity of infection of 10. This work increases the number of characterized bacteriophages infecting K. pneumoniae and provides information regarding genome sequence and efficacy during preclinical phage therapy against two prominent sublineages of this bacterial species.

Corrigendum: Allelic variation contributes to bacterial host specificity.

This corrects the article DOI: 10.1038/ncomms9754.

Existence of two groups of Staphylococcus aureus strains isolated from bovine mastitis based on biofilm formation, intracellular survival, capsular profile and agr-typing.

Staphylococcus (S.) aureus is recognised worldwide as an important pathogen causing contagious acute and chronic bovine mastitis. Chronic mastitis account for a significant part of all bovine cases and represent an important economic problem for dairy producers. Several properties (biofilm formation, intracellular survival, capsular expression and group agr) are thought to be associated with this chronic status. In a previous study, we found the existence of two groups of strains based on the association of these features. The aim of the present work was to confirm on a large international and non-related collection of strains the existence of these clusters and to associate them with case history records. In addition, the genomes of eight strains were sequenced to study the genomic differences between strains of each cluster. The results confirmed the existence of both groups based on capsular typing, intracellular survival and agr-typing: strains cap8-positive, belonging to agr group II, showing a low invasion rate and strains cap5-positive, belonging to agr group I, showing a high invasion rate. None of the two clusters were associated with the chronic status of the cow. When comparing the genomes of strains belonging to both clusters, the genes specific to the group "cap5-agrI" would suggest that these strains are better adapted to live in hostile environment. The existence of these two groups is highly important as they may represent two clusters that are adapted differently to the host and/or the surrounding environment.

Allelic variation contributes to bacterial host specificity.

Understanding the molecular parameters that regulate cross-species transmission and host adaptation of potential pathogens is crucial to control emerging infectious disease. Although microbial pathotype diversity is conventionally associated with gene gain or loss, the role of pathoadaptive nonsynonymous single-nucleotide polymorphisms (nsSNPs) has not been systematically evaluated. Here, our genome-wide analysis of core genes within Salmonella enterica serovar Typhimurium genomes reveals a high degree of allelic variation in surface-exposed molecules, including adhesins that promote host colonization. Subsequent multinomial logistic regression, MultiPhen and Random Forest analyses of known/suspected adhesins from 580 independent Typhimurium isolates identifies distinct host-specific nsSNP signatures. Moreover, population and functional analyses of host-associated nsSNPs for FimH, the type 1 fimbrial adhesin, highlights the role of key allelic residues in host-specific adherence in vitro. Together, our data provide the first concrete evidence that functional differences between allelic variants of bacterial proteins likely contribute to pathoadaption to diverse hosts.