title: Mycobacterium tuberculosis Rv0198c, a putative matrix metalloprotease is involved in pathogenicity.
abstract: We are interested in the role of proteases in the biology of the global human pathogen, Mycobacterium tuberculosis. We have focused on a putative matrix metalloprotease, Rv0198c. In order to investigate its role we constructed an unmarked chromosomal deletion of the gene and analysed the phenotype of the resulting mutant. No differences in growth in axenic culture were seen and there was no measurable change in overall protease activity in cell-free extracts. Transcriptome analysis revealed a small number of changes in gene expression in aerobic growth, with Rv2488c and Rv1971 being over 40-fold up-regulated and qor (Rv1454c) being 20-fold down-regulated; in addition, changes were seen in members of the heat shock regulon. Virulence assays demonstrated that the mutant was able to replicate in human macrophage-like cells (THP-1 cell line) to a comparable degree with the wild-type. However, the mutant was hyper-virulent in the SCID and C57BL/6 mouse models. Our data suggest that Rv0198c plays a role during infection.
authors.affiliation: Queen Mary University of London, Barts & The London School of Medicine and Dentistry, London E1 2AD, UK.
authors.forename: D G Niranjala
authors.initials: DG
authors.lastname: Muttucumaru
authors.forename: Debbie A
authors.initials: DA
authors.lastname: Smith
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: McMinn
authors.forename: Valerie
authors.initials: V
authors.lastname: Reese
authors.forename: Rhea N
authors.initials: RN
authors.lastname: Coler
authors.forename: Tanya
authors.initials: T
authors.lastname: Parish
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D002872:Chromosome Deletion; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D008168:Lung / Q000382:microbiology; D008264:Macrophages / Q000382:microbiology; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D009169:Mycobacterium tuberculosis / Q000201:enzymology* / Q000254:growth & development / Q000472:pathogenicity; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D013154:Spleen / Q000382:microbiology; D059467:Transcriptome; D014376:Tuberculosis / Q000382:microbiology; D014774:Virulence / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D020782:Matrix Metalloproteinases; C568229:Rv0198c protein, Mycobacterium tuberculosis