Anthracimycin activity against contemporary methicillin-resistant Staphylococcus aureus

TitleAnthracimycin activity against contemporary methicillin-resistant Staphylococcus aureus
Publication TypeJournal Article
Year of Publication2014
AuthorsHensler M.E, Jang K.H, Thienphrapa W., Vuong L., Tran D.N, Soubih E., Lin L., Haste N.M, Cunningham M.L, Kwan B.P, Shaw K.J, Fenical W, Nizet V.
JournalJournal of Antibiotics
Volume67
Pagination549-553
Date Published2014/08
Type of ArticleArticle
ISBN Number0021-8820
Accession NumberWOS:000341074600001
Keywordsactinomycete; anthracimycin; aureus; marine; methicillin-resistant; novel antibiotic; Staphylococcus; streptomyces sp
Abstract

Anthracimycin is a recently discovered novel marine-derived compound with activity against Bacillus anthracis. We tested anthracimycin against an expanded panel of Staphylococcus aureus strains in vitro and in vivo. All strains of S. aureus tested, including methicillin-susceptible, methicillin-resistant (MRSA) and vancomycin-resistant strains of S. aureus, were susceptible to anthracimycin at MIC values of <= 0.25 mg l(-1). Although its postantibiotic effects were minimal, anthracimycin exhibited potent and rapid bactericidal activity, with a >4-log kill of USA300 MRSA within 3 h at five times its MIC. At concentrations significantly below the MIC, anthracimycin slowed MRSA growth and potentiated the bactericidal activity of the human cathelicidin, LL-37. The bactericidal activity of anthracimycin was somewhat mitigated in the presence of 20% human serum, and the compound was minimally toxic to human cells, with an IC50 (inhibitory concentration 50)=70 mg l(-1) against human carcinoma cells. At concentrations near the MIC, anthracimycin inhibited S. aureus nucleic acid synthesis as determined by optimized macromolecular synthesis methodology, with inhibition of DNA and RNA synthesis occurring in the absence of DNA intercalation. Anthracimycin at a single dose of 1 or 10 mg kg(-1) was able to protect mice from MRSA-induced mortality in a murine peritonitis model of infection. Anthracimycin provides an interesting new scaffold for future development of a novel MRSA antibiotic.

DOI10.1038/ja.2014.36
Short TitleJ. Antibiot.
Integrated Research Themes: 
Student Publication: 
No
Research Topics: