The actinobacterial mce4 locus encodes a steroid transporter
William W Mohn1, Robert van der Geize, Gordon R Stewart
1Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver V6T 1Z3, Canada. wmohn@interchange.ubc.ca
The Journal of Biological Chemistry
|October 29, 2008
Summary
The Mce4 system in Rhodococcus jostii RHA1 is a steroid transporter. This discovery provides direct evidence for the function of Mce proteins in cholesterol uptake and metabolism.
Area of Science:
- Microbiology
- Biochemistry
- Molecular Biology
Background:
- ATP-binding cassette transporter systems, including Mce proteins, are found in actinobacteria.
- In Mycobacterium tuberculosis, Mce proteins are linked to host-pathogen interactions.
Purpose of the Study:
- To provide direct evidence for the function of the Mce4 system in Rhodococcus jostii RHA1.
- To investigate the role of the Mce4 system in steroid uptake and metabolism.
Main Methods:
- Transcriptional analysis of the mce4 operon.
- Growth studies of RHA1 on various sterols.
- Radiolabeled cholesterol uptake assays.
- Bioinformatic analysis of mce4 loci.
Main Results:
- The Mce4 system is encoded by an 11-gene operon, upregulated during growth on cholesterol.
- Expression of the mce4 operon is essential for cholesterol uptake and growth on sterols.
- Cholesterol uptake is ATP-dependent and follows Michaelis-Menten kinetics.
- Bioinformatic analysis links mce4 loci to steroid metabolism genes across genomes.
Conclusions:
- The Mce4 system in Rhodococcus jostii RHA1 functions as a steroid transporter.
- All Mce4 systems are predicted to be steroid transporters.
- This finding supports the role of cholesterol metabolism in M. tuberculosis pathogenesis.
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