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Identification of genetic markers of resistance to macrolide class antibiotics in Mannheimia haemolytica isolates from a Saskatchewan feedlot

Date

2024-06-12

Authors

Deschner, Darien
Voordouw, Maarten J.
Fernando, Champika
Campbell, John
Waldner, Cheryl L.
Hill, Janet E.

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Publisher

American Society for Microbiology [Society Publisher]

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Article

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Abstract

Mannheimia haemolytica is a major contributor to bovine respiratory disease (BRD), which causes substantial economic losses to the beef industry, and there is an urgent need for rapid and accurate diagnostic tests to provide evidence for treatment decisions and support antimicrobial stewardship. Diagnostic sequencing can provide information about antimicrobial resistance genes in M. haemolytica more rapidly than conventional diagnostics. Realizing the full potential of diagnostic sequencing requires a comprehensive understanding of the genetic markers of antimicrobial resistance. We identified genetic markers of resistance in M. haemolytica to macrolide class antibiotics commonly used for control of BRD. Genome sequences were determined for 99 M. haemolytica isolates with six different susceptibility phenotypes collected over 2 years from a feedlot in Saskatchewan, Canada. Known macrolide resistance genes estT, msr(E), and mph(E) were identified in most resistant isolates within predicted integrative and conjugative elements (ICEs). ICE sequences lacking antibiotic resistance genes were detected in 10 of 47 susceptible isolates. No resistance-associated polymorphisms were detected in ribosomal RNA genes, although previously unreported mutations in the L22 and L23 ribosomal proteins were identified in 12 and 27 resistant isolates, respectively. Pangenome analysis led to the identification of 79 genes associated with resistance to gamithromycin, of which 95% (75 of 79) had no functional annotation. Most of the observed phenotypic resistance was explained by previously identified antibiotic resistance genes, although resistance to the macrolides gamithromycin and tulathromycin was not explained in 39 of 47 isolates, demonstrating the need for continued surveillance for novel determinants of macrolide resistance.

Description

Accepted Manuscript Copyright © 2024 American Society for Microbiology. All Rights Reserved.

Keywords

Mannheimia haemolytica, antimicrobial agents, antibiotic resistance, cattle, macrolides, genomics, bovine respiratory disease

Citation

Deschner D, Voordouw MJ, Fernando C, Campbell J, Waldner CL, Hill JE. 2024. Identification of genetic markers of resistance to macrolide class antibiotics in Mannheimia haemolytica isolates from a Saskatchewan feedlot. Appl Environ Microbiol 90:e00502-24. https://doi.org/10.1128/aem.00502-24

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Citation

Deschner D, Voordouw MJ, Fernando C, Campbell J, Waldner CL, Hill JE. 2024. Identification of genetic markers of resistance to macrolide class antibiotics in Mannheimia haemolytica isolates from a Saskatchewan feedlot. Appl Environ Microbiol 90:e00502-24. https://doi.org/10.1128/aem.00502-24

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DOI

10.1128/aem.00502-24

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