Whole-Genome Sequencing Analysis Accurately Predicts Antimicrobial Resistance Phenotypes in Campylobacter spp

Zhao, Shaohua; Tyson, Gregory H.; Chen, Y.; Li, C.; Mukherjee, Sampa; Young, Shenia; Lam, Claudia; Folster, Jason P.; Whichard, Jean M.; McDermott, Patrick F.

doi:10.1128/aem.02873-15

Cited by 220 publications

(213 citation statements)

References 37 publications

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“…The ability to predict AMR phenotype from WGS data with high sensitivity and specificity has previously been observed in Salmonella enterica isolated from humans and retail meats (27) and S. Typhimurium from swine (28), as well as in other organisms, including Staphylococcus aureus (29,30) Campylobacter spp. (31), and Mycobacterium tuberculosis (30). The results of our study further attest to the robustness of WGS in predicting resistance phenotypes in Salmonella enterica serotypes Typhimurium, Newport, and Dublin from both bovine and human sources.…”

Section: Discussionmentioning

confidence: 61%

Whole-Genome Sequencing of Drug-Resistant Salmonella enterica Isolates from Dairy Cattle and Humans in New York and Washington States Reveals Source and Geographic Associations

Carroll

Bakker

Siler

et al. 2017

Appl Environ Microbiol

107

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Multidrug-resistant (MDR) Salmonella enterica can be spread from cattle to humans through direct contact with animals shedding Salmonella as well as through the food chain, making MDR Salmonella a serious threat to human health. The objective of this study was to use whole-genome sequencing to compare antimicrobial-resistant (AMR) Salmonella enterica serovars Typhimurium, Newport, and Dublin isolated from dairy cattle and humans in Washington State and New York State at the genotypic and phenotypic levels. A total of 90 isolates were selected for the study (37 S. Typhimurium, 32 S. Newport, and 21 S. Dublin isolates). All isolates were tested for phenotypic antibiotic resistance to 12 drugs using Kirby-Bauer disk diffusion. AMR genes were detected in the assembled genome of each isolate using nucleotide BLAST and ARG-ANNOT. Genotypic prediction of phenotypic resistance resulted in a mean sensitivity of 97.2 and specificity of 85.2. Sulfamethoxazole-trimethoprim resistance was observed only in human isolates (P Ͻ 0.05), while resistance to quinolones and fluoroquinolones was observed only in 6 S. Typhimurium isolates from humans in Washington State. S. Newport isolates showed a high degree of AMR profile similarity, regardless of source. S. Dublin isolates from New York State differed from those from Washington State based on the presence/absence of plasmid replicons, as well as phenotypic AMR susceptibility/nonsusceptibility (P Ͻ 0.05). The results of this study suggest that distinct factors may contribute to the emergence and dispersal of AMR S. enterica in humans and farm animals in different regions.IMPORTANCE The use of antibiotics in food-producing animals has been hypothesized to select for AMR Salmonella enterica and associated AMR determinants, which can be transferred to humans through different routes. Previous studies have sought to assess the degree to which AMR livestock-and human-associated Salmonella strains overlap, as well as the spatial distribution of Salmonella's associated AMR determinants, but have often been limited by the degree of resolution at which isolates can be compared. Here, a comparative genomics study of livestock-and humanassociated Salmonella strains from different regions of the United States shows that while many AMR genes and phenotypes were confined to human isolates, overlaps between the resistomes of bovine and human-associated Salmonella isolates were observed on numerous occasions, particularly for S. Newport. We have also shown that whole-genome sequencing can be used to reliably predict phenotypic resistance across Salmonella isolated from bovine sources.

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Section: Discussionmentioning

confidence: 61%

Whole-Genome Sequencing of Drug-Resistant Salmonella enterica Isolates from Dairy Cattle and Humans in New York and Washington States Reveals Source and Geographic Associations

Carroll

Bakker

Siler

et al. 2017

Appl Environ Microbiol

107

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“…Zhao et al (86) recently found that the Campylobacter genotype, using WGS, is predictive of antibiotic resistance phenotypes using 114 isolates of Campylobacter (C. jejuni and C. coli) and 18 antibiotic resistance genes. They found between 95% and 100% correlation to phenotype.…”

Section: Discussionmentioning

confidence: 99%

Genomic Comparison of Campylobacter spp. and Their Potential for Zoonotic Transmission between Birds, Primates, and Livestock

Weis

Storey

Taff

et al. 2016

Appl Environ Microbiol

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Campylobacter is the leading cause of human gastroenteritis worldwide. Wild birds, including American crows, are abundant in urban, suburban, and agricultural settings and are likely zoonotic vectors of Campylobacter. Their proximity to humans and livestock increases the potential spreading of Campylobacter via crows between the environment, livestock, and humans. However, no studies have definitively demonstrated that crows are a vector for pathogenic Campylobacter. We used genomics to evaluate the zoonotic and pathogenic potential of Campylobacter from crows to other animals with 184 isolates obtained from crows, chickens, cows, sheep, goats, humans, and nonhuman primates. Whole-genome analysis uncovered two distinct clades of Campylobacter jejuni genotypes; the first contained genotypes found only in crows, while a second genotype contained "generalist" genomes that were isolated from multiple host species, including isolates implicated in human disease, primate gastroenteritis, and livestock abortion. Two major ␤-lactamase genes were observed frequently in these genomes (oxa-184, 55%, and oxa-61, 29%), where oxa-184 was associated only with crows and oxa-61 was associated with generalists. Mutations in gyrA, indicative of fluoroquinolone resistance, were observed in 14% of the isolates. Tetracycline resistance (tetO) was present in 22% of the isolates, yet it occurred in 91% of the abortion isolates. Virulence genes were distributed throughout the genomes; however, cdtC alleles recapitulated the crow-only and generalist clades. A specific cdtC allele was associated with abortion in livestock and was concomitant with tetO. These findings indicate that crows harboring a generalist C. jejuni genotype may act as a vector for the zoonotic transmission of Campylobacter. IMPORTANCEThis study examined the link between public health and the genomic variation of Campylobacter in relation to disease in humans, primates, and livestock. Use of large-scale whole-genome sequencing enabled population-level assessment to find new genes that are linked to livestock disease. With 184 Campylobacter genomes, we assessed virulence traits, antibiotic resistance susceptibility, and the potential for zoonotic transfer to observe that there is a "generalist" genotype that may move between host species. Campylobacter is a motile Gram-negative spiral bacterium that causes gastroenteritis in humans and other animals (1, 2). In livestock, Campylobacter may cause abortion in addition to gastroenteritis (3). It is one of the most common foodborne zoonotic pathogens worldwide and is often transmitted via the fecal-oral route through the consumption of contaminated food or water (1, 2). In the United States, campylobacteriosis is estimated to affect more than 1.3 million people each year, with symptoms including fever, abdominal cramping, and bloody diarrhea (1, 4, 5). Internationally, campylobacteriosis is a significant public health burden; the incidence in developed nations is estimated to be 4.4 to 9.3 per 1,000 people yearly and...

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“…For most bacteria, the evidence for using WGS to infer antimicrobial susceptibility data is sparse, although some studies have shown a high correlation between resistance phenotypes and the presence of resistance genes or resistance-associated mutations. This agreement has been best demonstrated with enteric bacteria, including Escherichia coli, Campylobacter spp., and nontyphoidal Salmonella (8)(9)(10)(11)(12). In addition, other DNAbased methods have been used to detect resistance determinants and even guide therapy for infections caused by Mycobacterium tuberculosis, Staphylococcus aureus, HIV, and other pathogens (13)(14)(15).…”

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confidence: 99%

Establishing Genotypic Cutoff Values To Measure Antimicrobial Resistance in Salmonella

Tyson

Zhao

Liu

et al. 2017

Antimicrob Agents Chemother

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Whole-genome sequencing (WGS) has transformed our understanding of antimicrobial resistance, helping us to better identify and track the genetic mechanisms underlying phenotypic resistance. Previous studies have demonstrated high correlations between phenotypic resistance and the presence of known resistance determinants. However, there has never been a large-scale assessment of how well resistance genotypes correspond to specific MICs. We performed antimicrobial susceptibility testing and WGS of 1,738 nontyphoidal Salmonella strains to correlate over 20,000 MICs with resistance determinants. Using these data, we established what we term genotypic cutoff values (GCVs) for 13 antimicrobials against Salmonella. For the drugs we tested, we define a GCV as the highest MIC of isolates in a population devoid of known acquired resistance mechanisms. This definition of GCV is distinct from epidemiological cutoff values (ECVs or ECOFFs), which currently differentiate wild-type from non-wild-type strains based on MIC distributions alone without regard to genetic information. Due to the large number of isolates involved, we observed distinct MIC distributions for isolates with different resistance gene alleles, including for ciprofloxacin and tetracycline, suggesting the potential to predict MICs based on WGS data alone.

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Whole-Genome Sequencing Analysis Accurately Predicts Antimicrobial Resistance Phenotypes in Campylobacter spp

Cited by 220 publications

References 37 publications

Whole-Genome Sequencing of Drug-Resistant Salmonella enterica Isolates from Dairy Cattle and Humans in New York and Washington States Reveals Source and Geographic Associations

Whole-Genome Sequencing of Drug-Resistant Salmonella enterica Isolates from Dairy Cattle and Humans in New York and Washington States Reveals Source and Geographic Associations

Genomic Comparison of Campylobacter spp. and Their Potential for Zoonotic Transmission between Birds, Primates, and Livestock

Establishing Genotypic Cutoff Values To Measure Antimicrobial Resistance in Salmonella

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