Genetic changes associated with tigecycline resistance in Staphylococcus aureus in vitro-selected mutants belonging to different lineages

Tigecycline Resistance-Associated Mutations in the MepA Efflux Pump in Staphylococcus aureus

“…Each profile included abundant mutations. After whole-genome sequencing (WGS) for mutant strains selected in vitro , amino acid substitutions T29I and E287G were broadly detected in the mepA genes of selected mutants in this study, and T29I, E287G, V415A, and L441W were repeatedly detected in four other studies ( 22 – 25 ); all studies searched reported at least one in these four sites ( Fig. 1 ).…”

“…The mutations of MATE family efflux pump Tet(L) were discovered in Staphylococcus spp., and clone and expression experiments were performed to determine whether the mutations detected confer tigecycline resistance and pose the risk of clinical treatment failure ( 26 ). Mutations in mepA are frequently detected after laboratory evolution and in clinical isolates ( 22 – 25 ), but the role of diverse mutations on mepA in tigecycline resistance has not been confirmed.…”

“…The mepR gene encodes the substrate-responsive regulatory protein MepR and is the negative regulation factor of mepA ( 20 ), and the mutant mepR may inactivate MepR and cause mepA overexpression and confer resistance to tigecycline further ( 21 ). Apart from overexpression, mutations of mepA have been observed in adaptive laboratory evolution ( 22 – 24 ) and clinical isolates ( 25 ), but the associations between mutations on mepA and tigecycline resistance are still unclear.…”

New Antimicrobials for Gram-Positive Sustained Infections: A Comprehensive Guide for Clinicians

“…Tigecycline (TGC) resistance was also rarely associated with loss-of-function mutations in the transcriptional repressor mep R, resulting in a derepression and overexpression of the MepA efflux pump belonging to the multidrug and toxic compound extrusion (MATE) family of multidrug efflux pumps [ 11 ].…”