ArticlePloS one2015
Deletion of cyp125 Confers Increased Sensitivity to Azoles in Mycobacterium tuberculosis.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 12 citations in OpenAlex.
- Genomic variations in Mycobacterium tuberculosis from the lungs and blood of HIV-infected individuals in Uganda: insights into compartmentalization.African health sciences · 2024Article
- The prominent alteration in transcriptome and metabolome of Mycobacterium bovis BCG str. Tokyo 172 induced by vitamin BBMC microbiology · 2019Article
- Mutations in the anti-sigma H factor RshA confer resistance to econazole and clotrimazole inAccess microbiology · 2019Article
- Potential drug targets in the Mycobacterium tuberculosis cytochrome P450 system.Journal of inorganic biochemistry · 2018Review
- Cholesterol metabolism: a potential therapeutic target in Mycobacteria.British journal of pharmacology · 2017Review
- Imidazoles Induce Reactive Oxygen Species inACS omega · 2017Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mycobacterium tuberculosis is able to utilize cholesterol as a carbon source, and this ability is linked to its virulence in macrophages and in the mouse model of infection. The M. tuberculosis cytochrome P450 Cyp125 plays a key role in cholesterol metabolism being involved in the first steps of its degradation. Cyp125 is a cholesterol hydroxylase which is essential for cholesterol catabolism in M. bovis BCG and some strains of M. tuberculosis. We generated an unmarked, in-frame deletion of Cyp125 in M. tuberculosis H37Rv. The deletion strain was able to grow as well as wild-type in medium containing glucose as the carbon source. The Cyp125 deletion strain was more sensitive to growth inhibition by clotrimazole consistent with the ability of Cyp125 to bind azoles with high affinity. The deletion strain showed no difference in sensitivity to nitric oxide or hydrogen peroxide and was not attenuated for growth inside THP-1 human macrophage-like cells. These data suggest that the attenuation of virulence seen in operon deletion strains is not linked to the lack of Cyp125 alone.
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