title: Mycobacterium tuberculosis gene Rv2136c is dispensable for acid resistance and virulence in mice.
abstract: The gene Rv2136c is annotated to encode the Mycobacterium tuberculosis (Mtb) homolog of Escherichia coli's undecaprenyl pyrophosphate phosphatase. In previous work, a genetic screen of 10,100 Mtb transposon mutants identified Rv2136c as being involved in acid resistance in Mtb. The Rv2136c:Tn strain was also sensitive to sodium dodecyl sulfate, lipophilic antibiotics, elevated temperature and reactive oxygen and nitrogen intermediates and was attenuated for growth and persistence in mice. However, none of these phenotypes could be genetically complemented, leading us to generate an Rv2136c knockout strain to test its role in Mtb pathogenicity. Genetic deletion revealed that Rv2136c is not responsible for any of the phenotypes observed in the transposon mutant strain. An independent genomic mutation is likely to have accounted for the extreme attenuation of this strain. Identification of the mutated gene will further our understanding of acid resistance mechanisms in Mtb and may offer a target for anti-tuberculosis chemotherapy.
authors.affiliation: Department of Microbiology and Immunology, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA. darbycm@gmail.com
authors.forename: Crystal M
authors.initials: CM
authors.lastname: Darby
authors.forename: Aditya
authors.initials: A
authors.lastname: Venugopal
authors.forename: Sabine
authors.initials: S
authors.lastname: Ehrt
authors.forename: Carl F
authors.initials: CF
authors.lastname: Nathan
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D015139:Blotting, Southern; D005260:Female; D017353:Gene Deletion; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics*; D010587:Phagocytosis / Q000235:genetics*; D010588:Phagosomes / Q000235:genetics*; D010641:Phenotype; D060888:Real-Time Polymerase Chain Reaction; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D019883:Alkyl and Aryl Transferases; C499606:Rv2361c protein, Mycobacterium tuberculosis