2. A N Mason and
3. R F Bilton
The metabolic pathway of cholesterol degradation by bacteria has not been completely established. Several possible intermediates have not been identified and many pathway delineations have not involved the use of the cholesterol molecule per se and just one bacterial species. The bacterial degradation of cholesterol by Pseudomonas sp. NCIB has been studied. Major biotransformation products included cholest-5-en-3-one, cholest-4-en-3-one, 26-hydroxycholest-4-en-3-one, androsta-1, 4-dien-3-17-dione, cholest-4-en-3-one-26-oic acid, chol-4-en-3-one-24-oic acid, pregn-4-en-3-one-20-carboxylic acid, and pregna-1, 4-dien-3-one-20-carboxylic acid. Studies with selected intermediates have enabled the elucidation of a comprehensive pathway of cholesterol degradation by bacteria.
November 1983 The Journal of Lipid Research, 24, 1500-1511.
Mycobacterial persistence requires the utilization of host cholesterol
1. Amit K. Pandey and
2. Christopher M. Sassetti *
1. Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655
1. Edited by Barry R. Bloom, Harvard School of Public Health, Boston, MA, and approved January 22, 2008 (received for review November 26, 2007)
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 thatmce4 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-γ-activated macrophages that predominate at this stage of infection. This finding indicates that a major effect of IFN-γ 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.
Published online before print March 11, 2008, doi:10.1073/pnas.0711159105
Initial Steps in the Anoxic Metabolism of Cholesterol by the DenitrifyingSterolibacterium denitrificans*♦
1. Yin-Ru Chiang ‡ ,
2. Wael Ismail ‡ ,
3. Michael Müller § and
4. Georg Fuchs ‡ 1
1. ‡Mikrobiologie, Fakultät für Biologie, Universität Freiburg, Schänzlestrasse 1, D-79104 Freiburg, Germany and the §Institut für Pharmazeutische Wissenschaften, Universität Freiburg, Albertstrasse 25, D-79104 Freiburg, Germany 1. 1 To whom correspondence should be addressed. Tel.: 497612032649; Fax: 497612032626; E-mail: firstname.lastname@example.org.
The anoxic metabolism of the ubiquitous triterpene cholesterol is challenging because of its complex chemical structure, low solubility in water, low number of active functional groups, and the presence of four alicyclic rings and two quaternary carbon atoms. Consequently, the aerobic metabolism depends on oxygenase catalyzed reactions requiring molecular oxygen as co-substrate.Sterolibacterium denitrificans is shown to metabolize cholesterol anoxically via the oxidation of ring A, followed by an oxygen-independent hydroxylation of the terminal C-25 of the side chain. The anaerobic hydroxylation of a tertiary carbon using water as oxygen donor is...