Deletion of Causes Increased Sensitivity to -Aminosalicylic Acid and Sulfamethoxazole in Mycobacterium tuberculosis.

Although the folate biosynthesis pathway has been well studied in bacteria, little is known about its regulation. In the present study, the gene in was deleted. Subsequent drug susceptibility tests revealed that the Δ strain was more sensitive to -aminosalicylic acid (PAS) and sulfamethoxazole. Comparative transcriptional analysis was performed, and downregulation of was observed in the Δ strain, which was further verified by a quantitative reverse transcription-PCR and Western blot assay. Then, the production levels of -aminobenzoic acid (ABA) were compared between the deletion mutant and wild-type strain, and the results showed that deletion resulted in decreased production of ABA. In addition, SigB was able to recognize the promoter of Furthermore, we found that deleting also caused increased susceptibility to PAS. Taken together, our data revealed that, in , affects susceptibility to antifolates through multiple ways, primarily by regulating the expression of To our knowledge, this is the first report showing that SigB modulates ABA biosynthesis and thus affecting susceptibility to antifolates, which broadens our understanding of the regulation of bacterial folate metabolism and mechanisms of susceptibility to antifolates.