Mycobacterial persistence requires the utilization of host cholesterol
UMass Chan Affiliations
Department of Molecular Genetics and MicrobiologyDocument Type
Journal ArticlePublication Date
2008-03-13Keywords
Bacterial ProteinsCarbon
Cholesterol
Chronic Disease
Molecular Structure
Mycobacterium tuberculosis
Tuberculosis
Life Sciences
Medicine and Health Sciences
Microbiology
Metadata
Show full item recordAbstract
A hallmark of tuberculosis is the ability of the causative agent, Mycobacterium tuberculosis, to persist for decades despite a vigorous host immune response. Previously, we identified a mycobacterial gene cluster, mce4, that was specifically required for bacterial survival during this prolonged infection. We now show that mce4 encodes a cholesterol import system that enables M. tuberculosis to derive both carbon and energy from this ubiquitous component of host membranes. Cholesterol import is not required for establishing infection in mice or for growth in resting macrophages. However, this function is essential for persistence in the lungs of chronically infected animals and for growth within the IFN-gamma-activated macrophages that predominate at this stage of infection. This finding indicates that a major effect of IFN-gamma stimulation may be to sequester potential pathogens in a compartment devoid of more commonly used nutrients. The unusual capacity to catabolize sterols allows M. tuberculosis to circumvent this defense and thereby sustain a persistent infection.Source
Proc Natl Acad Sci U S A. 2008 Mar 18;105(11):4376-80. Epub 2008 Mar 11. Link to article on publisher's siteDOI
10.1073/pnas.0711159105Permanent Link to this Item
http://hdl.handle.net/20.500.14038/39199PubMed ID
18334639Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1073/pnas.0711159105