Battacin (Octapeptin B5), a New Cyclic Lipopeptide Antibiotic from Paenibacillus tianmuensis Active against Multidrug-Resistant Gram-Negative Bacteria

Abstract

Hospital-acquired infections caused by drug-resistant bacteria are a significant challenge to patient safety. Numerous clinical isolates resistant to almost all commercially available antibiotics have emerged. Thus, novel antimicrobial agents, specifically those for multidrug-resistant Gram-negative bacteria, are urgently needed. In the current study, we report the isolation, structure elucidation, and preliminary biological characterization of a new cationic lipopeptide antibiotic, battacin or octapeptin B5, produced from a Paenibacillus tianmuensis soil isolate. Battacin kills bacteria in vitro and has potent activity against Gramnegative bacteria, including multidrug-resistant and extremely drug-resistant clinical isolates. Hospital strains of Escherichia coli and Pseudomonas aeruginosa are the pathogens most sensitive to battacin, with MICs of 2 to 4 g/ml. The ability of battacin to disrupt the outer membrane of Gram-negative bacteria is comparable to that of polymyxin B, the last-line therapy for infections caused by antibiotic-resistant Gram-negative bacteria. However, the capacity of battacin to permeate bacterial plasma membranes is less extensive than that of polymyxin B. The bactericidal kinetics of battacin correlate with the depolarization of the cell membrane, suggesting that battacin kills bacteria by disrupting the cytoplasmic membrane. Other studies indicate that battacin is less acutely toxic than polymyxin B and has potent in vivo biological activity against E. coli. Based on the findings of the current study, battacin may be considered a potential therapeutic agent for the treatment of infections caused by antibioticresistant Gram-negative bacteria.

Characterization of the Antimicrobial Peptide Penisin, a Class Ia Novel Lantibiotic from Paenibacillus sp. Strain A3

“…After inoculation, the mice received peptide treatment (up to 100 mg/kg) i.p., once a day for the first day and twice daily for the next 3 days. Mice that survived 12, 24, or 72 h or 7 days after treatment were recorded, and the survival rate was calculated as described earlier (33). All experiments were carried out in a biosafety level 2 facility animal house at our institute.…”

“…To determine the bacterial load in the thighs, the homogenate was serially diluted in PBS and aliquots (50 l) of each dilution were plated on Trypticase soy broth (TSB; Himedia, India) plates. The plates were incubated for 18 h at 37°C, and bacterial colonies were counted (33).…”

Screening concepts, characterization and structural analysis of microbial-derived bioactive lipopeptides: a review

“…[126] A subsequent study identified GC-MS peaks that were characteristic of b-hydroxy fatty acid methyl derivatives. [127] The purified active compound was hydrolyzed with 6 M HCl at 110 C for 2 h in a sealed vial. Free fatty acids were converted to methyl esters and analyzed with a GC-MS.…”

Development of new polymyxin derivatives for multi-drug resistant Gram-negative infections

“…30 A related octapeptide, Battacin, Octapeptin B5 was isolated in 2012. 31 This is reported to have the D-amino acid at position 5 of the cyclic core, and this was recently confirmed by total synthesis. 32 …”