Kibdelomycin Is a Bactericidal Broad-Spectrum Aerobic Antibacterial Agent

• Published in: Antimicrobial agents and chemotherapy Vol. 59; no. 6; pp. 3474 - 3481
• Main Authors: Singh, Sheo B., Dayananth, Priya, Balibar, Carl J., Garlisi, Charles G., Lu, Jun, Kishii, Ryuta, Takei, Masaya, Fukuda, Yasumichi, Ha, Sookhee, Young, Katherine
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01.06.2015
• Subjects: Acinetobacter baumannii; Acinetobacter baumannii - drug effects; Anti-Bacterial Agents; Anti-Bacterial Agents - pharmacology; Clostridium difficile; Escherichia coli; Escherichia coli - drug effects; Experimental Therapeutics; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas aeruginosa - drug effects; Pyrroles; Pyrroles - pharmacology; Pyrrolidinones; Pyrrolidinones - pharmacology; Staphylococcus aureus; Staphylococcus aureus - drug effects; Streptococcus pneumoniae
• ISSN: 0066-4804; 1098-6596; 1098-6596
• DOI: 10.1128/AAC.00382-15

Bacterial resistance to antibiotics continues to grow and pose serious challenges, while the discovery rate for new antibiotics declines. Kibdelomycin is a recently discovered natural-product antibiotic that inhibits bacterial growth by inhibiting the bacterial DNA replication enzymes DNA gyrase and topoisomerase IV. It was reported to be a broad-spectrum aerobic Gram-positive agent with selective inhibition of the anaerobic bacterium Clostridium difficile . We have extended the profiling of kibdelomycin by using over 196 strains of Gram-positive and Gram-negative aerobic pathogens recovered from worldwide patient populations. We report the MIC 50 s, MIC 90 s, and bactericidal activities of kibdelomycin. We confirm the Gram-positive spectrum and report for the first time that kibdelomycin shows strong activity (MIC 90 , 0.125 μg/ml) against clinical strains of the Gram-negative nonfermenter Acinetobacter baumannii but only weak activity against Pseudomonas aeruginosa . We confirm that well-characterized resistant strains of Staphylococcus aureus and Streptococcus pneumoniae show no cross-resistance to kibdelomycin and quinolones and coumarin antibiotics. We also show that kibdelomycin is not subject to efflux in Pseudomonas , though it is in Escherichia coli , and it is generally affected by the outer membrane permeability entry barrier in the nonfermenters P. aeruginosa and A. baumannii , which may be addressable by structure-based chemical modification.