RshA mutations contributing to tigecycline resistance in Mycobacteroides abscessus

Abstract

Tigecycline is an important rescue antibiotic for many bacterial infections. In Mycobacteroides abscessus , tigecycline resistance has been associated with dysregulated stress response caused by aberrations in the interaction of the SigH and RshA factors. In this study, two tigecycline-resistant mutants of M. abscessus (CL5A and CL6A) with mutations in the rshA gene were studied using gene complementation, RT-qPCR and the bacterial adenylate cyclase two-hybrid (BACTH) system. The results supported the premise that mutations in the rshA interrupt the RshA–SigH interaction to cause the overexpression of the sigH gene that leads to tigecycline resistance or reduced susceptibility.