Mycobacterium tuberculosis Rv0494 Protein Contributes to Mycobacterial Persistence

Purpose: Fatty acid metabolism plays an important role in the survival and pathogenesis of Mycobacterium tuberculosis . During dormancy, lipids are considered to be the main source of energy. A previous study found that Rv0494 is a starvation-inducible, lipid-responsive transcriptional regulator. However, the role of Rv0494 in bacterial persister survival has not been studied. Methods: We constructed a Rv0494 deletion mutant strain of Mycobacterium tuberculosis H37Rv and evaluated the susceptibility of the mutant strain to antibiotics using a persistence test. Results: We found that mutations in Rv0494 lead to survival defects of persisters, which reflected in increased sensitivity to isoniazid. Conclusion: We conclude that Rv0494 is important for persister survival and may serve as a good target for developing new antibiotics that kill persister bacteria for improved treatment of persistent bacterial infections. Keywords: drug target, drug tolerance, lipids, persisters