The complete catalog of antimicrobial resistance secondary active transporters in Clostridioides difficile: evolution and drug resistance perspective

        Secondary active transporters move substances across cell membranes in both eukaryotic and prokaryotic organisms, using different electrochemical gradients and contributing to antibiotic resistance in pathogens. While primary active transporters in the Clostridium difficile 630 genome are fully cataloged, secondary active transporters are not. This study identified 147 secondary active transporters in C. difficile 630 from 27 families, with 50 (34%) likely involved in antimicrobial resistance (AMR). These AMR transporters belong to the AbgT, DMT, MFS, MATE, and RND families. The RND genes in C. difficile 630 are remnants from a common ancestor with other bacteria. Protein structure analysis revealed six new potential AMR transporters from the DMT, MATE, and MFS families. Pangenome analysis showed that half of the AMR transporters are accessory genes, indicating their role in adapting to antibiotic resistance. Gene expression studies confirmed their ability to respond to various antibiotics. These findings highlight the importance of AMR-secondary active transporters in antibiotic resistance and suggest they could be targeted to enhance existing antibiotic therapies.

Reference

Chanket W, Pipatthana M, Sangphukieo A, Harnvoravongchai P, Chankhamhaengdecha S, Janvilisri T, Phanchana M. The complete catalog of antimicrobial resistance secondary active transporters in Clostridioides difficile: evolution and drug resistance perspective. Comput Struct Biotechnol J. 2024 May 21;23:2358-2374.

DOI: 10.1016/j.csbj.2024.05.027