Author | Marques, Maria Angela M. | |
Author | Pinho, Marcia Berrêdo | |
Author | Rosa, Thabatta L. S. A. | |
Author | Pujari, Venugopal | |
Author | Lemes, Robertha M. R. | |
Author | Lery, Leticia M. S. | |
Author | Silva, Carlos Adriano M. | |
Author | Guimarães, Ana Carolina R. | |
Author | Atella, Georgia C. | |
Author | Wheat, William H. | |
Author | Brennam, Patrick J. | |
Author | Crick, Dean D. | |
Author | Belisle, John T. | |
Author | Pessolani, Maria Cristina V. | |
Access date | 2016-05-17T16:50:23Z | |
Available date | 2016-05-17T16:50:23Z | |
Document date | 2015 | |
Citation | MARQUES, Maria Angela M. et al. The essential role of cholesterol metabolism in the intracellular survival of Mycobacterium leprae is not coupled to central carbon metabolism and energy production. J. Bacteriol.,v.197, n.23, p.3698-3707. Dec. 2015. | pt_BR |
ISSN | 0021-9193 | |
URI | https://www.arca.fiocruz.br/handle/icict/14319 | |
Language | eng | pt_BR |
Publisher | American Society for Microbiology | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | Mycobacterium leprae | pt_BR |
Subject in Portuguese | Colesterol | pt_BR |
Subject in Portuguese | Infecção | pt_BR |
Subject in Portuguese | Hanseníase | pt_BR |
Subject in Portuguese | Estruturas celulares | pt_BR |
Title | The essential role of cholesterol metabolism in the intracellular survival of Mycobacterium 2 leprae is not coupled to central carbon metabolism and energy production | pt_BR |
Type | Article | pt_BR |
DOI | 10.1128/JB.00625-15 | |
Abstract | Mycobacterium leprae induces the formation of lipid droplets, which are recruited to pathogen-containing phagosomes in infected macrophages and Schwann cells. Cholesterol is among the lipids with increased abundance in M. leprae-infected cells, and intracellular survival relies on cholesterol accumulation. The present study investigated the capacity of M. leprae to acquire and metabolize cholesterol. In silico analyses showed that oxidation of cholesterol to cholest-4-en-3-one (cholestenone), the first step of cholesterol degradation catalyzed by the enzyme 3β-hydroxysteroid dehydrogenase (3β-HSD), is apparently the only portion of the cholesterol catabolic pathway seen in Mycobacterium tuberculosis preserved by M. leprae. Incubation of bacteria with radiolabeled cholesterol confirmed the in silico predictions. Radiorespirometry and lipid analyses performed after incubating M. leprae with [4-(14)C]cholesterol or [26-(14)C]cholesterol showed the inability of this pathogen to metabolize the sterol rings or the side chain of cholesterol as a source of energy and carbon. However, the bacteria avidly incorporated cholesterol and, as expected, converted it to cholestenone both in vitro and in vivo. Our data indicate that M. leprae has lost the capacity to degrade and utilize cholesterol as a nutritional source but retains the enzyme responsible for its oxidation to cholestenone. Thus, the essential role of cholesterol metabolism in the intracellular survival of M. leprae is uncoupled from central carbon metabolism and energy production. Further elucidation of cholesterol metabolism in the host cell during M. leprae infection will establish the mechanism by which this lipid supports M. leprae intracellular survival and will open new avenues for novel leprosy therapies.
Our study focused on the obligate intracellular pathogen Mycobacterium leprae and its capacity to metabolize cholesterol. The data make an important contribution for those interested in understanding the mechanisms of mycobacterial pathogenesis, since they indicate that the essential role of cholesterol for M. leprae intracellular survival does not rely on its utilization as a nutritional source. Our findings reinforce the complexity of cholesterol's role in sustaining M. leprae infection. Further elucidation of cholesterol metabolism in the host cell during M. leprae infection will establish the mechanism by which this lipid supports M. leprae intracellular survival and will open new avenues for novel leprosy therapies. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil / Colorado State University. Department of Microbiology, Immunology and Pathology. Fort Collins, CO, USA. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil | pt_BR |
Affilliation | Colorado State University. Department of Microbiology, Immunology and Pathology. Fort Collins, CO, USA | pt_BR |
Affilliation | Fundação Oswaldo Cruz.de Microbiologia Celular. Rio de Janeiro, RJ, Brasil Instituto Oswaldo Cruz. Laboratório | pt_BR |
Affilliation | Fundação Oswaldo Cruz.de Microbiologia Celular. Rio de Janeiro, RJ, Brasil Instituto Oswaldo Cruz. Laboratório | pt_BR |
Affilliation | Colorado State University. Department of Microbiology, Immunology and Pathology. Fort Collins, CO, USA | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica. Laboratório de Bioquímica de Lipídeos e Lipoproteínas. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Colorado State University. Department of Microbiology, Immunology and Pathology. Fort Collins, CO, USA | pt_BR |
Affilliation | Colorado State University. Department of Microbiology, Immunology and Pathology. Fort Collins, CO, USA | pt_BR |
Affilliation | Colorado State University. Department of Microbiology, Immunology and Pathology. Fort Collins, CO, USA | pt_BR |
Affilliation | Colorado State University. Department of Microbiology, Immunology and Pathology. Fort Collins, CO, USA | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
Subject | Mycobacterium leprae | pt_BR |
Subject | Cholesterol | pt_BR |
Subject | Infection | pt_BR |
Subject | Leprosy | pt_BR |
e-ISSN | 1098-5530 | |