Abstract:
:Ramoplanin is an actinomycetes-derived antibiotic with broad-spectrum activity against Gram-positive bacteria that has been evaluated in clinical trials for the treatment of gastrointestinal vancomycin-resistant enterococci (VRE) and Clostridium difficile infections. Recent studies have proposed that ramoplanin binds to bacterial membranes as a C2 symmetrical dimer that can sequester Lipid II, which causes inhibition of cell wall peptidoglycan biosynthesis and cell death. In this study, ramoplanin was shown to bind to anionic and zwitterionic membrane mimetics with a higher affinity for anionic membranes and to induce membrane depolarization of methicillin-susceptible Staphylococcus aureus (MSSA) ATCC 25923 at concentrations at or above the minimal bactericidal concentration (MBC). The ultrastructural effects of ramoplanin on S. aureus were also examined by transmission electron microscopy (TEM), and this showed dramatic changes to bacterial cell morphology. The correlation observed between membrane depolarization and bacterial cell viability suggests that this mechanism may contribute to the bactericidal activity of ramoplanin.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Cheng M,Huang JX,Ramu S,Butler MS,Cooper MAdoi
10.1128/AAC.00061-14subject
Has Abstractpub_date
2014-11-01 00:00:00pages
6819-27issue
11eissn
0066-4804issn
1098-6596pii
AAC.00061-14journal_volume
58pub_type
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