Mce3R, a TetR-type transcriptional repressor, controls the expression of a regulon involved in lipid metabolism in Mycobacterium tuberculosis.
The mce operons constitute four homologous regions in the Mycobacterium tuberculosis genome, each of which has 8-13 ORFs. Although the function of the Mce protein family has not been clearly established, its members are believed to be membrane lipid transporters. Based on functional experiments, we found that the regulator of the mce3 locus, Mce3R, negatively regulates the expression of the Rv1933c-Rv1935c and Rv1936-Rv1941 transcriptional units. These operons are adjacent to one another and divergently transcribed. The predicted functions of most of these genes are related to either lipid metabolism or redox reactions. Bioinformatic analysis of the 5' UTR sequences of the differentially expressed genes allowed us to define a putative Mce3R motif. Importantly, the Mce3R motif was present six and three times in the mce3R-yrbE3A and Rv1935c-Rv1936 intergenic regions, respectively. Two occurrences of this motif mapped within the two regions of the mce3 operon that were protected by Mce3R in a footprinting analysis, thus indicating that this motif is likely to serve as an operator site for the Mce3R regulator in the promoter. In addition, alterations in the lipid content of M. tuberculosis were detected in the absence of Mce3R. Taken together, these results suggest that Mce3R controls the expression of both the putative transport system encoded in the mce3 operon and the enzymes implicated in the modification of the Mce3-transported substrates.
Santangelo
María de la Paz
MP
Instituto de Biotecnología, CICVyA-INTA, N. Repetto and De los Reseros, 1686 Hurlingham, Argentina.
Klepp
Laura
L
Instituto de Biotecnología, CICVyA-INTA, N. Repetto and De los Reseros, 1686 Hurlingham, Argentina.
Nuñez-García
Javier
J
Veterinary Laboratories Agency (Weybridge), New Haw, Addlestone, Surrey KT15 3NB, UK.
Blanco
Federico C
FC
Instituto de Biotecnología, CICVyA-INTA, N. Repetto and De los Reseros, 1686 Hurlingham, Argentina.
Soria
Marcelo
M
Microbiología Agrícola Facultad de Agronomía, Universidad de Buenos Aires, Av. San Martin 4453, 1417 Buenos Aires, Argentina.
García-Pelayo
Maria Del Carmen
MDC
Veterinary Laboratories Agency (Weybridge), New Haw, Addlestone, Surrey KT15 3NB, UK.
Bianco
María Verónica
MV
Instituto de Biotecnología, CICVyA-INTA, N. Repetto and De los Reseros, 1686 Hurlingham, Argentina.
Cataldi
Angel A
AA
Instituto de Biotecnología, CICVyA-INTA, N. Repetto and De los Reseros, 1686 Hurlingham, Argentina.
Golby
Paul
P
Veterinary Laboratories Agency (Weybridge), New Haw, Addlestone, Surrey KT15 3NB, UK.
Jackson
Mary
M
Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523-1682, USA.
Gordon
Stephen V
SV
Veterinary Laboratories Agency (Weybridge), New Haw, Addlestone, Surrey KT15 3NB, UK.
Bigi
Fabiana
F
Instituto de Biotecnología, CICVyA-INTA, N. Repetto and De los Reseros, 1686 Hurlingham, Argentina.
D000818:Animals; D001426:Bacterial Proteins / Q000502:physiology*; D001483:Base Sequence; D002460:Cell Line; D017124:Conserved Sequence; D004269:DNA, Bacterial / Q000032:analysis / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D050356:Lipid Metabolism; D008055:Lipids / Q000032:analysis; D051379:Mice; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010084:Oxidation-Reduction; D011401:Promoter Regions, Genetic; D018085:Regulon; D012097:Repressor Proteins / Q000502:physiology*
D001426:Bacterial Proteins; D004269:DNA, Bacterial; D008055:Lipids; D012097:Repressor Proteins