Antimycobacterial activity of bacteriocins and their complexes with liposomes.
OBJECTIVE
Bacteriocins (Bcn) are natural peptides that are secreted by several taxonomically distant bacteria and exert bactericidal activity against other bacterial species. Their capacity to inhibit growth of virulent Mycobacterium tuberculosis H37Rv was evaluated in this study.


METHODS
Five different Bcn were isolated and purified from bacterial culture supernatants, their amino acid sequence was determined, and activity against mycobacteria assessed in three different models: in vitro mycobacterial cultures, in vitro infection of mouse macrophages and in vivo high-dose infection of inbred mice.


RESULTS
In the in vitro model, four out of five Bcn exhibited stronger antimycobacterial activity than equal concentrations of a widely used anti-TB antibiotic, rifampicin. These Bcn were non-toxic for mouse macrophages at a concentration of 0.1 mg/L (>MIC(90) of these compounds). Pure Bcn did not inhibit mycobacterial growth within murine macrophages when added at 0.01-0.1 mg/L, suggesting that at physiologically tolerable concentrations these molecules do not penetrate through the membrane of eukaryotic cells. However, when administered as a complex with phosphatidylcholine-cardiolipin liposomes, Bcn5 (selected as a model compound due to its cytotoxicity and antimycobacterial activity regular titration curves) demonstrated capacity both to inhibit intracellular growth of M. tuberculosis and to prolong survival of mice in an acute TB model.


CONCLUSIONS
Given that the mechanism of Bcn bactericidal activity differs from that of all commonly used antibiotics, their possible involvement in complex TB therapies deserves further study.
Sosunov
Vasily
V
Laboratory for Immunogenetics, Central Institute for Tuberculosis, Moscow, Russia.
Mischenko
Vladimir
V
Eruslanov
Boris
B
Svetoch
Edward
E
Shakina
Yulia
Y
Stern
Norman
N
Majorov
Konstantin
K
Sorokoumova
Galina
G
Selishcheva
Alla
A
Apt
Alexander
A
D000818:Animals; D000904:Antibiotics, Antitubercular / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000494:pharmacology; D001430:Bacteriocins / Q000008:administration & dosage / Q000494:pharmacology*; D008081:Liposomes; D017737:Macrophages, Peritoneal / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D012293:Rifampin / Q000494:pharmacology
D000904:Antibiotics, Antitubercular; D000995:Antitubercular Agents; D001430:Bacteriocins; D008081:Liposomes; D012293:Rifampin