| Summary: | <i>Mycobacteroides abscessus</i> (formerly <i>Mycobacterium abscessus</i>) is a clinically important, rapid-growing non-tuberculous mycobacterium notoriously known for its multidrug-resistance phenotype. The intrinsic resistance of <i>M. abscessus</i> towards first- and second-generation tetracyclines is mainly due to the over-expression of a tetracycline-degrading enzyme known as MabTetX (<i>MAB_1496c</i>). Tigecycline, a third-generation tetracycline, is a poor substrate for the MabTetX and does not induce the expression of this enzyme. Although tigecycline-resistant strains of <i>M. abscessus</i> have been documented in different parts of the world, their resistance determinants remain largely elusive. Recent work on tigecycline resistance or reduced susceptibility in <i>M. abscessus</i> revealed the involvement of the gene <i>MAB_3508c</i> which encodes the transcriptional activator WhiB7, as well as mutations in the <i>sigH-rshA</i> genes which control heat shock and oxidative-stress responses. The deletion of <i>whiB7</i> has been observed to cause a 4-fold decrease in the minimum inhibitory concentration of tigecycline. In the absence of environmental stress, the SigH sigma factor (<i>MAB_3543c</i>) interacts with and is inhibited by the anti-sigma factor RshA (<i>MAB_3542c</i>). The disruption of the SigH-RshA interaction resulting from mutations and the subsequent up-regulation of SigH have been hypothesized to lead to tigecycline resistance in <i>M. abscessus</i>. In this review, the evidence for different genetic determinants reported to be linked to tigecycline resistance in <i>M. abscessus</i> was examined and discussed.
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