RshA mutations contributing to tigecycline resistance in Mycobacteroides abscessus

<jats:p>Tigecycline is an important rescue antibiotic for many bacterial infections. In <jats:italic>
<jats:named-content content-type="species">
<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://doi.org/10.1601/nm.31320" xlink:type="simple">Mycobacteroides abscessus</jats:ext-link>
</jats:named-content>
</jats:italic>, 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 <jats:italic>
<jats:named-content content-type="species">
<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://doi.org/10.1601/nm.31320" xlink:type="simple">M. abscessus</jats:ext-link>
</jats:named-content>
</jats:italic> (CL5A and CL6A) with mutations in the <jats:italic>rshA</jats:italic> 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 <jats:italic>rshA</jats:italic> interrupt the RshA–SigH interaction to cause the overexpression of the <jats:italic>sigH</jats:italic> gene that leads to tigecycline resistance or reduced susceptibility.</jats:p>