探究碳青霉烯耐药肺炎克雷伯菌双组分系统对多粘菌素耐药的影响
Journal: Basic Medical Theory Research DOI: 10.12238/bmtr.v7i6.17069
Abstract
目的：本研究旨在分析耐多粘菌素和耐碳青霉烯肺炎克雷伯菌（Polymyxin resistant and Carbapenemase - resistant Klebsiella pneumoniae，PR-CRKP）的双组分系统对多粘菌素耐药的影响，为多粘菌素耐药机制研究基础提供参考。方法：收集2019年6月-2022年12月南部战区总医院临床标本检出的PR-CRKP共37株，通过PCR扩增多粘菌素耐药相关的双组分系统调控基因（mgrB，phoP，phoQ，pmrA，pmrB）并进行测序及比对；使用荧光实时定量PCR（RT-qPCR）比较其在多粘菌素耐药组及敏感组中表达量的差异。结果：PCR检测结果显示37株PR-CRKP mgrB突变率为100%，包括插入突变及点突变等8种突变类型，pmrA、phoP和phoQ均为野生型，有23 株PR-CRKP存在pmrB R256G突变，1株为A160T突变。RT-qPCR结果显示，多粘菌素敏感组与耐药组之间mgrB、phoP和phoQ整体表达量存在显著差异，但pmrB和pmrA基因的表达量两组间并无显著差异。结论：ISKpn26的插入使mgrB的表达量显著下降，phoP与phoQ基因相对表达量升高，pmrA与pmrB升高不显著，表明该插入片段使mgrB对PhoP/PhoQ具有负调控作用，从而导致多粘菌素耐药；IS903B插入对mgrB表达无显著影响，但phoP和phoQ的表达量升高，其他mgrB突变类型也存在mgrB相对表达活跃，说明双组分系统的表达未被抑制，提示可能存在其他通路或者影响因素影响多粘菌素耐药。
Keywords
多粘菌素耐药；mgrB；耐碳青霉烯肺炎克雷伯菌
Full Text
PDF - Viewed/Downloaded: 0 TimesReferences
[1] Jayol A, Nordmann P, Brink A, et al. Heteroresistance to Colistin in Klebsiella pneumoniae Associated with Alterations in the PhoPQ Regulatory System[J]. Antimicrobial Agents and Chemotherapy,2015,59(5):2780-2784.
[2] Cannatelli A, Giani T, D’Andrea M M, et al. MgrB Inactivation Is a Common Mechanism of Colistin Resistance in KPC-Producing Klebsiella pneumoniae of Clinical Origin[J]. Antimicrobial Agents and Chemotherapy, 2014, 58(10): 5696-5703.
[3] Huang J, Li C, Song J, et al. Regulating polymyxin resistance in Gram-negative bacteria: roles of two-component systems PhoPQ and PmrAB[J]. Future Microbiology, 2020, 15(6): 445–459.
[4] Poirel L, Jayol A, Bontron S, et al.The mgrB gene as a key target for acquired resistance to colistin in Klebsiella pneumoniae[J]. Journal of Antimicrobial Chemotherapy, 2015, 70(1):75–80.
[5] 胡付品,郭燕,朱德妹,等.2021年CHINET中国细菌耐药监测[J].中国感染与化疗杂志,2022,22(5):521-530.
[6] Cheng Y-H, Lin T-L, Pan Y-J, et al. Colistin Resistance Mechanisms in Klebsiella pneumoniae Strains from Taiwan[J]. Antimicrobial Agents and Chemotherapy, 2015, 59(5): 2909-2913.
[7] Xu Q, Xu T, Zhuang Y, et al. In Vivo Development of Polymyxin B Resistance in Klebsiella pneumoniae owing to a 42 bp Deletion in the Sequence of phoQ[J]. BioMed Research International, 2020, 2020: 1-6.
[8] Uz Zaman T, Albladi M, Siddique M I, et al. Insertion element mediated mgrB disruption and presence of ISKpn28 in colistin-resistant Klebsiella pneumoniae isolates from Saudi Arabia[J]. Infection and Drug Resistance, 2018, 11: 1183-1187.
[9] 胡黄都.浙江省碳青霉烯耐药肺炎克雷伯菌多黏菌素耐药机制研究[D].浙江大学,2020.
[2] Cannatelli A, Giani T, D’Andrea M M, et al. MgrB Inactivation Is a Common Mechanism of Colistin Resistance in KPC-Producing Klebsiella pneumoniae of Clinical Origin[J]. Antimicrobial Agents and Chemotherapy, 2014, 58(10): 5696-5703.
[3] Huang J, Li C, Song J, et al. Regulating polymyxin resistance in Gram-negative bacteria: roles of two-component systems PhoPQ and PmrAB[J]. Future Microbiology, 2020, 15(6): 445–459.
[4] Poirel L, Jayol A, Bontron S, et al.The mgrB gene as a key target for acquired resistance to colistin in Klebsiella pneumoniae[J]. Journal of Antimicrobial Chemotherapy, 2015, 70(1):75–80.
[5] 胡付品,郭燕,朱德妹,等.2021年CHINET中国细菌耐药监测[J].中国感染与化疗杂志,2022,22(5):521-530.
[6] Cheng Y-H, Lin T-L, Pan Y-J, et al. Colistin Resistance Mechanisms in Klebsiella pneumoniae Strains from Taiwan[J]. Antimicrobial Agents and Chemotherapy, 2015, 59(5): 2909-2913.
[7] Xu Q, Xu T, Zhuang Y, et al. In Vivo Development of Polymyxin B Resistance in Klebsiella pneumoniae owing to a 42 bp Deletion in the Sequence of phoQ[J]. BioMed Research International, 2020, 2020: 1-6.
[8] Uz Zaman T, Albladi M, Siddique M I, et al. Insertion element mediated mgrB disruption and presence of ISKpn28 in colistin-resistant Klebsiella pneumoniae isolates from Saudi Arabia[J]. Infection and Drug Resistance, 2018, 11: 1183-1187.
[9] 胡黄都.浙江省碳青霉烯耐药肺炎克雷伯菌多黏菌素耐药机制研究[D].浙江大学,2020.
Copyright © 2025 黄小煌, 朱姿婧, 卜仕君, 陈曦, 陈丽丹
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License