New bisanthraquinone antibiotics and semi-synthetic derivatives with potent activity against clinical Staphylococcus aureus and Enterococcus faecium isolates.
The escalation of antibiotic resistance among Gram-positive pathogens presents increasing treatment challenges and requires the development of innovative therapeutic agents. Here, we present the antimicrobial properties of structurally unusual bisanthraquinone metabolites produced by a marine streptomycete and four semi-synthetic derivatives. Biological activities were measured against clinically derived isolates of vancomycin-resistant Enterococcus faecium (VRE), and methicillin-susceptible, methicillin-resistant, and tetracycline-resistant Staphylococcus aureus (MSSA, MRSA, and TRSA, respectively). The most potent antibiotic displayed MIC(50) values of 0.11, 0.23, and 0.90microM against a panel (n=25 each) of clinical MSSA, MRSA, and VRE, respectively, and was determined to be bactericidal by time-kill analysis.
Socha
Aaron M
AM
Department of Biomedical, University of Rhode Island, 53 Fogarty Hall Kingston, RI 02881, USA.
LaPlante
Kerry L
KL
Rowley
David C
DC
D000880:Anthraquinones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002478:Cells, Cultured / Q000187:drug effects; D016984:Enterococcus faecium / Q000187:drug effects*; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects*; D013753:Tetracycline Resistance; D020713:Vancomycin Resistance; D014769:Virginiamycin
D000880:Anthraquinones; D000900:Anti-Bacterial Agents; D014769:Virginiamycin