title: Role of folP1 and folP2 Genes in the Action of Sulfamethoxazole and Trimethoprim Against Mycobacteria.
abstract: The combination of trimethoprim (TMP) and sulfamethoxazole (SMX) has been shown to be active against Mycobacterium tuberculosis (Mtb) in clinical tuberculosis (TB) treatment. However, the mechanism of action of TMP-SMX against Mtb is still unknown. To unravel this, we have studied the effect of TMP and SMX by deleting the folP2 gene in Mycobacterium smegmatis (Msm), and overexpressing the Mtb and Msm folP1/2 genes in Msm. Knocking out of the folP2 gene in Msm reduced the minimum inhibitory concentration of SMX 8-fold compared with wild type. Overexpression of the folP1 genes from Mtb and Msm increased the MICs by 4- and 2-fold in Msm for SMX and TMP, respectively. We show a strong correlation between the expression of folP1 and folP2 genes and TMP-SMX resistance in mycobacteria. This suggests that a combination of FolP2 inhibitor and SMX could be used for TB treatment with a better outcome.
authors.affiliation: School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, P.R. China.|State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, P.R. China.
authors.forename: Tianzhou
authors.initials: T
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, P.R. China.|School of Life Sciences, Anhui University, Hefei, Anhui 230601, P.R. China.
authors.forename: Bangxing
authors.initials: B
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, P.R. China.
authors.forename: Jintao
authors.initials: J
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, P.R. China.
authors.forename: Mugweru
authors.initials: M
authors.lastname: Julius
authors.affiliation: State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, P.R. China.
authors.forename: Moses
authors.initials: M
authors.lastname: Njire
authors.affiliation: State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, P.R. China.|School of Life Sciences, Anhui University, Hefei, Anhui 230601, P.R. China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, P.R. China.
authors.forename: Tian
authors.initials: T
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, P.R. China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, P.R. China.
authors.forename: Changwei
authors.initials: C
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, P.R. China.
authors.forename: Tianyu
authors.initials: T
authors.lastname: Zhang
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D017353:Gene Deletion; D015870:Gene Expression; D005798:Genes, Bacterial; D008826:Microbial Sensitivity Tests; D020102:Mycobacterium smegmatis / Q000187:drug effects* / Q000235:genetics; D009169:Mycobacterium tuberculosis / Q000235:genetics; D013420:Sulfamethoxazole / Q000494:pharmacology*; D014295:Trimethoprim / Q000494:pharmacology*
chemical_list: D000995:Antitubercular Agents; D014295:Trimethoprim; D013420:Sulfamethoxazole
keywords: Mycobacteria; folP1; folP2; sulfamethoxazole; trimethoprim