title: Statins increase rifampin mycobactericidal effect.
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.
authors: Laboratório de Microbiologia Celular, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Lívia Silva
authors: LS
authors: Lobato
authors: Lauro de Sousa Lima Institute, Department of Biology, Bauru, São Paulo, Brazil.
authors: Patrícia Sammarco
authors: PS
authors: Rosa
authors: Laboratório de Microbiologia Celular, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Jessica da Silva
authors: Jda S
authors: Ferreira
authors: Laboratório de Microbiologia Celular, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Arthur da Silva
authors: Ada S
authors: Neumann
authors: Laboratório de Micobactérias, Instituto de Microbiologia Professor Paulo de Góes, Cidade Universitária, Rio de Janeiro, Brazil.
authors: Marlei Gomes
authors: MG
authors: da Silva
authors: Lauro de Sousa Lima Institute, Department of Biology, Bauru, São Paulo, Brazil.
authors: Dejair Caitano
authors: DC
authors: do Nascimento
authors: Lauro de Sousa Lima Institute, Department of Biology, Bauru, São Paulo, Brazil.
authors: Cleverson Teixeira
authors: CT
authors: Soares
authors: Lauro de Sousa Lima Institute, Department of Biology, Bauru, São Paulo, Brazil.
authors: Silvia Cristina Barbosa
authors: SC
authors: Pedrini
authors: Laboratório de Microbiologia Celular, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Diego Sá Leal de
authors: DS
authors: Oliveira
authors: Lauro de Sousa Lima Institute, Department of Biology, Bauru, São Paulo, Brazil.
authors: Cláudia Peres
authors: CP
authors: Monteiro
authors: Laboratório de Microbiologia Celular, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Geraldo Moura Batista
authors: GM
authors: Pereira
authors: Centro de Pesquisa Clínica em HIV/AIDS, Evandro Chagas Clinical Research Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
authors: Marcelo
authors: M
authors: Ribeiro-Alves
authors: Laboratório de Hanseníase, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Mariana Andrea
authors: MA
authors: Hacker
authors: Laboratório de Hanseníase, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Milton Ozório
authors: MO
authors: Moraes
authors: Laboratório de Microbiologia Celular, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Maria Cristina Vidal
authors: MC
authors: Pessolani
authors: Laboratório de Micobactérias, Instituto de Microbiologia Professor Paulo de Góes, Cidade Universitária, Rio de Janeiro, Brazil.
authors: Rafael Silva
authors: RS
authors: Duarte
authors: Laboratório de Microbiologia Celular, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Rio de Janeiro, Brazil flavioalveslara2000@gmail.com.
authors: Flávio Alves
authors: FA
authors: Lara
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000627:therapeutic use*; D000069059:Atorvastatin; D002460:Cell Line; D004357:Drug Synergism; D006538:Heptanoic Acids / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007918:Leprosy / Q000188:drug therapy; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009166:Mycobacterium leprae / Q000187:drug effects* / Q000472:pathogenicity*; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000472:pathogenicity; D011758:Pyrroles / Q000627:therapeutic use; D012293:Rifampin / Q000627:therapeutic use*; D019821:Simvastatin / Q000627:therapeutic use
chemical_list: D000995:Antitubercular Agents; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin; D019821:Simvastatin; D012293:Rifampin