Antimicrobial Agents and Chemotherapy 2014-10-01

Statins increase rifampin mycobactericidal effect.

Lívia Silva Lobato, Patrícia Sammarco Rosa, Jessica da Silva Ferreira, Arthur da Silva Neumann, Marlei Gomes da Silva, Dejair Caitano do Nascimento, Cleverson Teixeira Soares, Silvia Cristina Barbosa Pedrini, Diego Sá Leal de Oliveira, Cláudia Peres Monteiro, Geraldo Moura Batista Pereira, Marcelo Ribeiro-Alves, Mariana Andrea Hacker, Milton Ozório Moraes, Maria Cristina Vidal Pessolani, Rafael Silva Duarte, Flávio Alves Lara

Index: Antimicrob. Agents Chemother. 58(10) , 5766-74, (2014)

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Abstract

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.