Title

Mycobacterial persistence requires the utilization of host cholesterol

UMMS Affiliation

Department of Molecular Genetics and Microbiology

Publication Date

3-13-2008

Document Type

Article

Subjects

Bacterial Proteins; Carbon; Cholesterol; Chronic Disease; Molecular Structure; Mycobacterium tuberculosis; Tuberculosis

Disciplines

Life Sciences | Medicine and Health Sciences | Microbiology

Abstract

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.

Rights and Permissions

Citation: Proc Natl Acad Sci U S A. 2008 Mar 18;105(11):4376-80. Epub 2008 Mar 11. Link to article on publisher's site

DOI of Published Version

10.1073/pnas.0711159105

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Proceedings of the National Academy of Sciences of the United States of America

PubMed ID

18334639