Department of Microbiology and Immunology, College of Basic Medicine, Guangdong Medical University, Zhanjiang, China.
Department of Anesthesiology and Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
Microb Drug Resist. 2021 Oct;27(10):1405-1411. doi: 10.1089/mdr.2020.0395. Epub 2021 Apr 9.
A clinically isolated pan-resistant strain (ST11), KPN142 was subjected to whole-genome sequencing. Genomic sequence of KPN142 showed that limited antibiotic resistances (β-lactams [], sulfonamides [ and ], bacitracin [], tetracycline [], aminoglycosides [, , , , and ], and chloramphenicol []) were mediated by enzymes, and efflux pumps contributed most to pan resistance. Five types of multidrug resistance efflux pump families were identified, including the resistance nodulation division superfamily (AcrAB-TolC, AcrD, MdtABC, and KexD), the ATP-binding cascade superfamily (MacAB), the small multidrug resistance family (KpnEF), the multidrug and toxic compound extrusion family (KdeA), and the major facilitator superfamily (EmrAB). There was an AcrAB-TolC efflux pump system, and inhibitory regulatory gene and of system carried deletion mutation, which lead to overexpression of AcrAB-TolC efflux pump, and in turn plays key role in the pan resistance of KPN142. Moreover, we did not find , a suppressor in the expression of , overexpression of which may confer the resistance of KPN142 to colistin B. In addition, KPN142 carries IS1, IS3, and , which means that KPN142 is able to transfer drug-resistance genes. Of note, we detected the overexpression of , , , and by real-time quantitative reverse transcription-polymerase chain reaction, and carbonyl cyanide chlorophenylhydrazone was able to reverse the resistance patterns of KPN142. In conclusion, we consider that the overexpression of AcrAB-TolC efflux pump mediates the resistance to most common clinical antimicrobial agents, and the overexpression of mediates the resistance to colistin B in KPN142.
一株临床分离的泛耐药株（ST11）KPN142 进行了全基因组测序。KPN142 的基因组序列表明，有限的抗生素耐药性（β-内酰胺类 []、磺胺类 []、杆菌肽 []、四环素类 []、氨基糖苷类 []、氯霉素 []）是由酶介导的，而外排泵对泛耐药性的贡献最大。鉴定出了 5 种多药耐药外排泵家族，包括耐药结节分裂超家族（AcrAB-TolC、AcrD、MdtABC 和 KexD）、ATP 结合盒超家族（MacAB）、小多药耐药家族（KpnEF）、多药和毒性化合物外排家族（KdeA）和主要易化子超家族（EmrAB）。存在 AcrAB-TolC 外排泵系统，系统的抑制调节基因 和 发生缺失突变，导致 AcrAB-TolC 外排泵过度表达，进而在 KPN142 的泛耐药性中发挥关键作用。此外，我们在 中没有发现表达的抑制子，其过表达可能赋予 KPN142 对多粘菌素 B 的耐药性。此外，KPN142 携带 IS1、IS3 和 ，这意味着 KPN142 能够转移耐药基因。值得注意的是，我们通过实时定量逆转录聚合酶链反应检测到 、 、 和 的过表达，羰基氰基氯苯腙能够逆转 KPN142 的耐药模式。总之，我们认为 AcrAB-TolC 外排泵的过度表达介导了对大多数常见临床抗菌药物的耐药性，而 的过度表达介导了 KPN142 对多粘菌素 B 的耐药性。
