Tuberculosis treatment failure associated with evolution of antibiotic resilience.

Journal:
Science (New York, N.Y.), Volume: 378, Issue: 6624
Published:
December 9, 2022
PMID:
36480634
Authors:
Qingyun Liu Q, Junhao Zhu J, Charles L Dulberger CL, Sydney Stanley S, Sean Wilson S, Eun Seon Chung ES, Xin Wang X, Peter Culviner P, Yue J Liu YJ, Nathan D Hicks ND, Gregory H Babunovic GH, Samantha R Giffen SR, Bree B Aldridge BB, Ethan C Garner EC, Eric J Rubin EJ, Michael C Chao MC, Sarah M Fortune SM
Abstract:

The widespread use of antibiotics has placed bacterial pathogens under intense pressure to evolve new survival mechanisms. Genomic analysis of 51,229 ()clinical isolates has identified an essential transcriptional regulator, , herein called for resilience regulator, as a frequent target of positive (adaptive) selection. mutants do not show canonical drug resistance or drug tolerance but instead shorten the post-antibiotic effect, meaning that they enable to resume growth after drug exposure substantially faster than wild-type strains. We refer to this phenotype as antibiotic resilience. ResR acts in a regulatory cascade with other transcription factors controlling cell growth and division, which are also under positive selection in clinical isolates of . Mutations of these genes are associated with treatment failure and the acquisition of canonical drug resistance.