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Aims
Staphylococcus aureus is a common bacterial species associated with bovine mastitis in dairy cattle globally, including in Taiwan. This study investigates the in vitro selection, reversal, and mutations associated with beta-lactam antimicrobial resistance in S. aureus.
Methods and results
Resistance was induced in a susceptible strain of S. aureus through serial in vitro exposure to increasing concentrations of ampicillin sodium salt, cefapirin, cefuroxime sodium salt, and cefquinome. The resulting resistant isolates significantly increased minimum inhibitory concentrations (MICs), with up to thousands of fold increases in resistance compared to the susceptible strain. Upon removal of the antimicrobial selection pressure, a reversal of resistance observed, with MICs declining by up to approximately 32-fold compared to the resistance-induced isolates. Cross-resistance was evaluated in the resistance-induced isolates, revealing varying degrees of resistance to tested antimicrobials. Whole genome sequencing was employed to identify mutations associated with resistance, and several resistance-associated mutations were detected in the penicillin-binding proteins, ABC transporter ATP-binding protein, cell wall–active antibiotics response protein, cyclic-di-AMP phosphodiesterase and two-component system sensor histidine kinase. Additionally, these mutations were investigated in the S. aureus isolates collected from mastitis-infected dairy cows. The mutations were detected and correlated with observed MICs.
Conclusions
The present findings will be valuable for understanding beta-lactam resistance in S. aureus and implementing strategies to mitigate resistance in the treatment of bovine mastitis.
Keywords: Staphylococcus aureus, Beta-lactam resistance, Whole genome sequencing, Protein mutation
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- Huynh T. Q., V. N. Tran, V. C. Thai, H. A. Nguyen, N. T. G. Nguyen, M. K. Tran, T. P. T. Nguyen, C. A. Le, L. T. N. Ho, N. U. Surian, S. Chen,T. T. H. Nguyen. 2023. Genomic alterations involved in fluoroquinolone resistance development in Staphylococcus aureus. PLoS One. 26;18(7):e0287973. doi: 10.1371/journal.pone.0287973
- Basuino, L., A. Jousselin, J. A. N. Alexander, N. C. J. Strynadka, M. G. Pinho, H. F. Chambers, and S. S. Chatterjee. 2018. PBP4 activity and its overexpression are necessary for PBP4-mediated high-level β-lactam resistance. J Antimicrob. Chemother. 73:1177–1180. https://doi.org/10.1093/jac/dkx531.
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