Centre for Research on Communicable Diseases, Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Selangor, Malaysia.
J Med Microbiol. 2021 Jul;70(7). doi: 10.1099/jmm.0.001378.
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.
替加环素目前被认为是治疗 感染最有效的抗生素之一。 替加环素耐药的遗传决定因素尚未得到很好的理解。 在这项研究中，我们对一株替加环素耐药的 突变株 CL7 进行了特征分析，以确定潜在的耐药机制。 通过抗菌药物敏感性试验、全基因组测序、PCR 和 RT-qPCR 对 CL7 进行了表征。 为了进行生物学验证，进行了基因过表达实验。 全基因组测序和随后的基因过表达实验表明，CL7 携带 c 中的无义突变，这可能是导致替加环素耐药表型的原因。 该基因编码 SigH 的同源物，SigH 参与生理应激反应的正调控，并且受到 中的 RshA 反西格玛因子的负调控。 我们假设 MAB_3543 c 突变可能破坏 SigH 和 RshA 之间的相互作用（MAB_3542 c）。 RT-qPCR 分析显示 c 和其他关键应激反应基因的上调，这以前被认为是 SigH-RshA 键断裂和替加环素耐药的标志。 MAB_3543c 突变可能是 中替加环素耐药的一个新决定因素。 本研究的结果有望为我们在 中了解潜在的替加环素耐药机制提供帮助，这可能为未来提供更好的诊断和治疗方法。
