1887

Abstract

Tigecycline is currently acknowledged to be one of the most effective antibiotics against infections caused by .

The genetic determinants of tigecycline resistance in are not well understood.

In this study, we characterized a tigecycline-resistant mutant, designated CL7, to identify the potential resistance mechanism.

CL7 was characterized using antimicrobial susceptibility testing, whole-genome sequencing, PCR and RT-qPCR. For biological verification, gene overexpression assays were carried out.

Whole-genome sequencing and the subsequent gene overexpression assays showed that CL7 harboured a stop–gain mutation in c, which may be responsible for the tigecycline resistance phenotype. This gene encodes an orthologue of SigH, which is involved in the positive regulation of physiological stress response and is negatively regulated by the RshA anti-sigma factor in . We hypothesized that the MAB_3543 c mutation may disrupt the interaction between SigH and RshA (MAB_3542 c). RT-qPCR analyses revealed the upregulation of c and other key stress response genes, which has previously been shown to be a hallmark of SigH–RshA bond disruption and tigecycline resistance.

The MAB_3543c mutation may represent a novel determinant of tigecycline resistance in . The findings of this study will hopefully contribute to our knowledge of potential tigecycline resistance mechanisms in , which may lead to better diagnostics and treatment modalities in the future.

Funding
This study was supported by the:
  • UTARRF (Award IPSR/RMC/UTARRF/2018-C2/N03 (6200/N51) and IPSR/RMC/UTARRF/2019-C2/T07 (6200/TG6))
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2021-07-08
2021-08-02
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