Antimicrobial Susceptibility and Resistance Mechanisms in Mannheimia haemolytica Isolates from Sheep at Slaughter

Simple Summary Mannheimia haemolytica is a key bacterial pathogen contributing to important ruminant diseases and accounting for a large proportion of overall antimicrobial use in cattle and sheep. The recent emergence of ovine strains with reduced susceptibility to antimicrobials-which could lead to treatment failure, increased costs of livestock production, and the dissemination of antimicrobial-resistant genes to other bacteria and possibly the environment-is of concern. This study investigated the levels of antimicrobial resistance of M. haemolytica isolated from clinically healthy sheep at slaughter and the genetic bacterial resistance mechanisms. Low levels of phenotypic resistance were detected for most of the antimicrobials tested except for tetracycline (4.3%) and tylosin (89.1%). A few antimicrobial resistance determinants were found in the genome of six out of nine isolates, consisting of genes conferring resistance to tetracyclines (tetH), aminoglycosides (strA), and sulfonamides (sul2), which were sometimes linked to the presence of plasmids but did not always lead to resistance phenotypes. Our results suggest that there is limited resistance in M. haemolytica strains of veterinary origin, but the presence of several resistance genes, some of which were found in mobile genetic elements that play a major role in the dissemination of antimicrobial resistance in members of the Pasteurellaceae family, deserves further consideration. Mannheimia haemolytica is the main pathogen contributing to pneumonic pasteurellosis in sheep. The aim of this study was to investigate the antimicrobial resistance levels in M. haemolytica isolates from the lungs of slaughtered sheep and to examine the genetic resistance mechanisms involved. A total of 256 M. haemolytica isolates, 169 from lungs with pneumonic lesions and 87 from lungs without lesions, were analyzed by the disk diffusion method for 12 antimicrobials, and the whole genome of 14 isolates was sequenced to identify antimicrobial resistance determinants. Levels of phenotypic resistance ranged from <2% for 10 antimicrobials (amoxicillin, amoxicillin-clavulanic, ceftiofur, cefquinome, lincomycin/spectinomycin, gentamicin, erythromycin, florfenicol, enrofloxacin, and doxycycline) to 4.3% for tetracycline and 89.1% for tylosin. Six isolates carried tetH genes and four isolates carried, in addition, the strA and sul2 genes in putative plasmid sequences. No mutations associated with macrolide resistance were identified in 23 rDNA sequences, suggesting that the M. haemolytica phenotypic results for tylosin should be interpreted with care in the absence of well-established epidemiological and clinical breakpoints. The identification of strains phenotypically resistant to tetracycline and of several resistance genes, some of which were present in plasmids, highlights the need for continuous monitoring of susceptibility patterns in Pasteurellaceae isolates from livestock.

Automated summary

This study investigates the antimicrobial resistance levels and genetic resistance mechanisms of M. haemolytica isolated from clinically healthy sheep at slaughter. The results show that most antimicrobials have low levels of resistance except for tetracycline and tylosin. However, several resistance genes, some of which are associated with plasmids, are found in the genome of some isolates, indicating the need for further attention.