Statins increase rifampin mycobactericidal effect.

Autor:	Lobato LS; Laboratório de Microbiologia Celular, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Rio de Janeiro, Brazil., Rosa PS; Lauro de Sousa Lima Institute, Department of Biology, Bauru, São Paulo, Brazil., Ferreira Jda S; Laboratório de Microbiologia Celular, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Rio de Janeiro, Brazil., Neumann Ada S; Laboratório de Microbiologia Celular, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Rio de Janeiro, Brazil., da Silva MG; Laboratório de Micobactérias, Instituto de Microbiologia Professor Paulo de Góes, Cidade Universitária, Rio de Janeiro, Brazil., do Nascimento DC; Lauro de Sousa Lima Institute, Department of Biology, Bauru, São Paulo, Brazil., Soares CT; Lauro de Sousa Lima Institute, Department of Biology, Bauru, São Paulo, Brazil., Pedrini SC; Lauro de Sousa Lima Institute, Department of Biology, Bauru, São Paulo, Brazil., Oliveira DS; Laboratório de Microbiologia Celular, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Rio de Janeiro, Brazil., Monteiro CP; Lauro de Sousa Lima Institute, Department of Biology, Bauru, São Paulo, Brazil., Pereira GM; Laboratório de Microbiologia Celular, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Rio de Janeiro, Brazil., Ribeiro-Alves M; Centro de Pesquisa Clínica em HIV/AIDS, Evandro Chagas Clinical Research Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., Hacker MA; Laboratório de Hanseníase, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Rio de Janeiro, Brazil., Moraes MO; Laboratório de Hanseníase, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Rio de Janeiro, Brazil., Pessolani MC; Laboratório de Microbiologia Celular, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Rio de Janeiro, Brazil., Duarte RS; Laboratório de Micobactérias, Instituto de Microbiologia Professor Paulo de Góes, Cidade Universitária, Rio de Janeiro, Brazil., Lara FA; Laboratório de Microbiologia Celular, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Rio de Janeiro, Brazil flavioalveslara2000@gmail.com.
Jazyk:	angličtina
Zdroj:	Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2014 Oct; Vol. 58 (10), pp. 5766-74. Date of Electronic Publication: 2014 Jul 21.
DOI:	10.1128/AAC.01826-13
Abstrakt:	Mycobacterium leprae and Mycobacterium tuberculosis antimicrobial resistance has been followed with great concern during the last years, while the need for new drugs able to control leprosy and tuberculosis, mainly due to extensively drug-resistant tuberculosis (XDR-TB), is pressing. Our group recently showed that M. leprae is able to induce lipid body biogenesis and cholesterol accumulation in macrophages and Schwann cells, facilitating its viability and replication. Considering these previous results, we investigated the efficacies of two statins on the intracellular viability of mycobacteria within the macrophage, as well as the effect of atorvastatin on M. leprae infections in BALB/c mice. We observed that intracellular mycobacteria viability decreased markedly after incubation with both statins, but atorvastatin showed the best inhibitory effect when combined with rifampin. Using Shepard's model, we observed with atorvastatin an efficacy in controlling M. leprae and inflammatory infiltrate in the BALB/c footpad, in a serum cholesterol level-dependent way. We conclude that statins contribute to macrophage-bactericidal activity against Mycobacterium bovis, M. leprae, and M. tuberculosis. It is likely that the association of statins with the actual multidrug therapy effectively reduces mycobacterial viability and tissue lesion in leprosy and tuberculosis patients, although epidemiological studies are still needed for confirmation. (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)
Databáze:	MEDLINE
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