Genetic Determinants of Tigecycline Resistance in Mycobacteroides abscessus

(formerly ) is a clinically important, rapid-growing non-tuberculous mycobacterium notoriously known for its multidrug-resistance phenotype. The intrinsic resistance of towards first- and second-generation tetracyclines is mainly due to the over-expression of a tetracycline-degrading enzyme known as MabTetX ( ). 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 have been documented in different parts of the world, their resistance determinants remain largely elusive. Recent work on tigecycline resistance or reduced susceptibility in revealed the involvement of the gene which encodes the transcriptional activator WhiB7, as well as mutations in the genes which control heat shock and oxidative-stress responses. The deletion of 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 ( ) interacts with and is inhibited by the anti-sigma factor RshA ( ). 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 . In this review, the evidence for different genetic determinants reported to be linked to tigecycline resistance in was examined and discussed.