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JAC Advance Access originally published online on March 8, 2007
Journal of Antimicrobial Chemotherapy 2007 59(5):919-925; doi:10.1093/jac/dkm053
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© The Author 2007. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Antimycobacterial activity of bacteriocins and their complexes with liposomes

Vasily Sosunov1, Vladimir Mischenko1, Boris Eruslanov2, Edward Svetoch2, Yulia Shakina3, Norman Stern4, Konstantin Majorov1, Galina Sorokoumova3, Alla Selishcheva3,5 and Alexander Apt1,*

1 Laboratory for Immunogenetics, Central Institute for Tuberculosis, Moscow, Russia 2 State Research Center for Applied Microbiology, Obolensk, Russia 3 M. V. Lomonosov Moscow State Academy of Fine Chemical Technology, Moscow, Russia 4 US Department of Agriculture, Agriculture Research Service, Russell Research Center, Athens, GA, USA 5 Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia

Received 5 November 2006; returned 8 January 2007; revised 23 January 2007; accepted 1 February 2007

* Corresponding author. Fax: +7495-963-80-00; E-mail: asapt{at}aha.ru

Objectives: 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 (>MIC90 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.

Keywords: tuberculosis chemotherapy , mouse model , Mycobacterium tuberculosis


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