Literature DB >> 25907064

Role of folP1 and folP2 Genes in the Action of Sulfamethoxazole and Trimethoprim Against Mycobacteria.

Tianzhou Liu1,2, Bangxing Wang2,3, Jintao Guo2, Yang Zhou2, Mugweru Julius2, Moses Njire2, Yuanyuan Cao2,3, Tian Wu2, Zhiyong Liu2, Changwei Wang2, Yong Xu2, Tianyu Zhang2.   

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.

Entities:  

Keywords:  Mycobacteria; folP1; folP2; sulfamethoxazole; trimethoprim

Mesh:

Substances:

Year:  2015        PMID: 25907064     DOI: 10.4014/jmb.1503.03053

Source DB:  PubMed          Journal:  J Microbiol Biotechnol        ISSN: 1017-7825            Impact factor:   2.351


  11 in total

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