Response of Methicillin-Resistant Staphylococcus aureus to Amicoumacin A

摘要: Amicoumacin A exhibits strong antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA), hence we sought to uncover its mechanism of action. Genome-wide transcriptome analysis S. COL in response amicoumacin showed alteration transcription genes specifying several cellular processes including cell envelope turnover, cross-membrane transport, virulence, metabolism, and general stress response. The most highly induced gene was lrgA, encoding an antiholin-like product, which is cells undergoing a collapse Δψ. Consistent with the notion that LrgA modulates murein hydrolase activity, grown presence reduced autolysis, primarily caused by lower activity. To gain further insight into action A, whole genome comparison wild-type A-resistant mutants isolated serial passage method carried out. Single point mutations generating codon substitutions were uncovered ksgA (encoding RNA dimethyltransferase), fusA (elongation factor G), dnaG (primase), lacD (tagatose 1,6-bisphosphate aldolase), SACOL0611 (a putative glycosyl transferase). EF-G cause resistance fusidic acid reside separate domains do not bring about cross resistance. Taken together, these results suggest might perturbation membrane lead energy dissipation. Decreased rates metabolism protein synthesis DNA replication resistant strains allow compensate for dysfunction thus increase survivability.