A Structurally Characterized
            <i>Staphylococcus aureus</i>
            Evolutionary Escape Route from Treatment with the Antibiotic Linezolid

Perlaza-Jiménez, Laura; Tan, Kher-Shing; Piper, Sarah; Johnson, Rachel M.; Bamert, Rebecca S.; Stubenrauch, Christopher J.; Wright, Alexander; Lupton, David W.; Lithgow, Trevor; Belousoff, Matthew J.

doi:10.1128/spectrum.00583-22

Cited by 4 publications

(1 citation statement)

References 46 publications

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“…Furthermore, the mutation of domain V of the 23S rRNA [ 121 ] and mutation of the ribosomal proteins near the linezolid binding site in the ribosomal peptidyl transferase center [ 128 ] results in linezolid resistance in MRSA. Multiple MRSA clones with two mutations in the ribosomal protein uL3 exhibited resistance to linezolid, with a two-fold higher MIC than the clinical breakpoint [ 243 ].…”

Section: Mrsa Resistance To Non-β-lactamsmentioning

confidence: 99%

Molecular Basis of Non-β-Lactam Antibiotics Resistance in Staphylococcus aureus

2022

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Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most successful human pathogens with the potential to cause significant morbidity and mortality. MRSA has acquired resistance to almost all β-lactam antibiotics, including the new-generation cephalosporins, and is often also resistant to multiple other antibiotic classes. The expression of penicillin-binding protein 2a (PBP2a) is the primary basis for β-lactams resistance by MRSA, but it is coupled with other resistance mechanisms, conferring resistance to non-β-lactam antibiotics. The multiplicity of resistance mechanisms includes target modification, enzymatic drug inactivation, and decreased antibiotic uptake or efflux. This review highlights the molecular basis of resistance to non-β-lactam antibiotics recommended to treat MRSA infections such as macrolides, lincosamides, aminoglycosides, glycopeptides, oxazolidinones, lipopeptides, and others. A thorough understanding of the molecular and biochemical basis of antibiotic resistance in clinical isolates could help in developing promising therapies and molecular detection methods of antibiotic resistance.

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Section: Mrsa Resistance To Non-β-lactamsmentioning

confidence: 99%