Evolutionary genomic analyses of canine E. coli infections identify a relic capsular locus associated with resistance to multiple classes of antimicrobials.

Autor:	Ceres K; Cornell University, Ithaca, New York, USA., Zehr JD; Cornell University, Ithaca, New York, USA., Murrell C; Cornell University, Ithaca, New York, USA., Millet JK; Université Paris-Saclay, INRAE, UVSQ, Virologie et Immunologie Moléculaires, Jouy-en-Josas, Paris, France., Sun Q; Cornell University, Ithaca, New York, USA., McQueary HC; Cornell University, Ithaca, New York, USA., Horton A; Cornell University, Ithaca, New York, USA., Cazer C; Cornell University, Ithaca, New York, USA., Sams K; Cornell University, Ithaca, New York, USA., Reboul G; Cornell University, Ithaca, New York, USA., Andreopoulos WB; San José State University, San José, California, USA., Mitchell PK; Cornell University, Ithaca, New York, USA., Anderson R; Cornell University, Ithaca, New York, USA., Franklin-Guild R; Cornell University, Ithaca, New York, USA., Cronk BD; Cornell University, Ithaca, New York, USA., Stanhope BJ; Cornell University, Ithaca, New York, USA., Burbick CR; Washington Animal Disease Diagnostic Laboratory, Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington, USA., Wolking R; Washington Animal Disease Diagnostic Laboratory, Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington, USA., Peak L; Louisiana Animal Disease Diagnostic Laboratory, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, USA., Zhang Y; Ohio Department of Agriculture Animal Disease Diagnostic Laboratory, Reynoldsburg, Ohio, USA., McDowall R; University of Guelph, Animal Health Laboratory, Guelph, Ontario, Canada., Krishnamurthy A; University of Guelph, Animal Health Laboratory, Guelph, Ontario, Canada., Slavic D; University of Guelph, Animal Health Laboratory, Guelph, Ontario, Canada., Sekhon Pk; South Dakota State University, Brookings, South Dakota, USA., Tyson GH; US Food and Drug Administration, Veterinary Laboratory Investigation and Response Network, Laurel, Maryland, USA., Ceric O; US Food and Drug Administration, Veterinary Laboratory Investigation and Response Network, Laurel, Maryland, USA., Stanhope MJ; Cornell University, Ithaca, New York, USA., Goodman LB; Cornell University, Ithaca, New York, USA.
Jazyk:	angličtina
Zdroj:	Applied and environmental microbiology [Appl Environ Microbiol] 2024 Aug 21; Vol. 90 (8), pp. e0035424. Date of Electronic Publication: 2024 Jul 16.
DOI:	10.1128/aem.00354-24
Abstrakt:	Infections caused by antimicrobial-resistant Escherichia coli are the leading cause of death attributed to antimicrobial resistance (AMR) worldwide, and the known AMR mechanisms involve a range of functional proteins. Here, we employed a pan-genome wide association study (GWAS) approach on over 1,000 E. coli isolates from sick dogs collected across the US and Canada and identified a strong statistical association (empirical P < 0.01) of AMR, involving a range of antibiotics to a group 1 capsular (CPS) gene cluster. This cluster included genes under relaxed selection pressure, had several loci missing, and had pseudogenes for other key loci. Furthermore, this cluster is widespread in E. coli and Klebsiella clinical isolates across multiple host species. Earlier studies demonstrated that the octameric CPS polysaccharide export protein Wza can transmit macrolide antibiotics into the E. coli periplasm. We suggest that the CPS in question, and its highly divergent Wza, functions as an antibiotic trap, preventing antimicrobial penetration. We also highlight the high diversity of lineages circulating in dogs across all regions studied, the overlap with human lineages, and regional prevalence of resistance to multiple antimicrobial classes. Importance: Much of the human genomic epidemiology data available for E. coli mechanism discovery studies has been heavily biased toward shiga-toxin producing strains from humans and livestock. E. coli occupies many niches and produces a wide variety of other significant pathotypes, including some implicated in chronic disease. We hypothesized that since dogs tend to share similar strains with their owners and are treated with similar antibiotics, their pathogenic isolates will harbor unexplored AMR mechanisms of importance to humans as well as animals. By comparing over 1,000 genomes with in vitro antimicrobial susceptibility data from sick dogs across the US and Canada, we identified a strong multidrug resistance association with an operon that appears to have once conferred a type 1 capsule production system. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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