Biosynthesis and Regulation of Sulfomenaquinone, a Metabolite Associated with Virulence in Mycobacterium tuberculosis
| Autor: | Daniel K. Nomura, Gabriela K. Fragiadakis, Kimberly M. Sogi, Cynthia M. Holsclaw, Carolyn R. Bertozzi, Julie A. Leary |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Tuberculosis Operon Mutant Virulence 01 natural sciences Article Microbiology Mycobacterium tuberculosis 03 medical and health sciences Mice Bacterial Proteins medicine Animals Humans Gene biology 010405 organic chemistry Cytochrome P450 Vitamin K 2 biology.organism_classification medicine.disease Phenotype 0104 chemical sciences 030104 developmental biology Infectious Diseases biology.protein |
| Zdroj: | ACS infectious diseases. 2(11) |
| ISSN: | 2373-8227 |
| Popis: | Sulfomenaquinone (SMK) is a recently identified metabolite that is unique to the Mycobacterium tuberculosis (M. tuberculosis) complex and is shown to modulate its virulence. Here, we report the identification of the SMK biosynthetic operon that, in addition to a previously identified sulfotransferase stf 3, includes a putative cytochrome P450 gene (cyp128) and a gene of unknown function, rv2269c. We demonstrate that cyp128 and stf 3 are sufficient for the biosynthesis of SMK from menaquinone and rv2269c exhibits promoter activity in M. tuberculosis. Loss of Stf3 expression, but not that of Cyp128, is correlated with elevated levels of menaquinone-9, an essential component in the electron-transport chain in M. tuberculosis. Finally, we showed in a mouse model of infection that the loss of cyp128 exhibits a hypervirulent phenotype similar to that in previous studies of the stf 3 mutant. These findings provide a platform for defining the molecular basis of SMK’s role in M. tuberculosis pathogenesis. |
| Databáze: | OpenAIRE |
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