1Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Malaysia.
2Faculty of Information Science and Technology, Multimedia University, Malaysia.
J Med Microbiol. 2018 Dec;67(12):1676-1681. doi: 10.1099/jmm.0.000857. Epub 2018 Oct 23.
In this study, we characterized 7C, a spontaneous mutant selected from tigecycline-susceptible Mycobacterium abscessus ATCC 19977. Whole-genome sequencing (WGS) was used to identify possible resistance determinants in this mutant. Compared to the wild-type, 7C demonstrated resistance to tigecycline as well as cross-resistance to imipenem, and had a slightly retarded growth rate. WGS and subsequent biological verifications showed that these phenotypes were caused by a point mutation in MAB_3542c, which encodes an RshA-like protein. In Mycobacterium tuberculosis, RshA is an anti-sigma factor that negatively regulates the heat/oxidative stress response mechanisms. The MAB_3542c mutation may represent a novel determinant of tigecycline resistance. We hypothesize that this mutation may dysregulate the stress-response pathways which have been shown to be linked to antibiotic resistance in previous studies.
在这项研究中，我们对从替加环素敏感的脓肿分枝杆菌 ATCC 19977 中筛选出的自发突变体 7C 进行了表征。全基因组测序 (WGS) 用于鉴定该突变体中可能的耐药决定因素。与野生型相比，7C 对替加环素表现出耐药性以及对亚胺培南的交叉耐药性，并且生长速度略有延迟。WGS 和随后的生物学验证表明，这些表型是由编码 RshA 样蛋白的 MAB_3542c 中的点突变引起的。在结核分枝杆菌中，RshA 是一种反西格玛因子，可负调控热/氧化应激反应机制。MAB_3542c 突变可能代表替加环素耐药的一个新决定因素。我们假设这种突变可能会使应激反应途径失调，先前的研究表明这些途径与抗生素耐药性有关。
