Rv0684/fusA1, an Essential Gene, Is the Target of Fusidic Acid and Its Derivatives in Mycobacterium tuberculosis.
Vinayak SinghGodwin Akpeko DziwornuAmanda MabhulaKelly ChibalePublished in: ACS infectious diseases (2021)
Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a major global health concern given the increase in multiple forms of drug-resistant TB. This underscores the importance of a continuous pipeline of new anti-TB agents. Drug repurposing has shown promise in expanding the therapeutic options for TB chemotherapy. Fusidic acid (FA), a natural product-derived antibiotic, is one such candidate for repurposing. The present study aimed to understand the mechanism of action of FA and its selected analogs in M. tuberculosis. By using chemical biology and genetics, we identified elongation factor G as the target of FA in M. tuberculosis. We showed essentiality of its encoding gene fusA1 in M. tuberculosis by demonstrating that the transcriptional silencing of fusA1 is bactericidal in vitro and in macrophages. Thus, this work validated a novel drug target FusA1 in M. tuberculosis.
Keyphrases
- mycobacterium tuberculosis
- drug resistant
- pulmonary tuberculosis
- global health
- multidrug resistant
- acinetobacter baumannii
- public health
- genome wide
- gene expression
- squamous cell carcinoma
- dna methylation
- oxidative stress
- emergency department
- transcription factor
- radiation therapy
- adverse drug
- molecular docking
- drug induced
- hepatitis c virus
- electronic health record
- artificial intelligence
- human immunodeficiency virus
- molecular dynamics simulations
- hiv infected