Acquisition of Tigecycline Resistance by Carbapenem-Resistant Klebsiella pneumoniae Confers Collateral Hypersensitivity to Aminoglycosides.
Acquisition of Tigecycline Resistance by Carbapenem-Resistant Klebsiella pneumoniae Confers Collateral Hypersensitivity to Aminoglycosides.
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耐碳青霉烯类肺炎克雷伯菌获得替加环素耐药性导致对氨基糖苷类药物过敏
DOI：
10.3389/fmicb.2021.674502
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发表时间：
2021
影响因子：
5.2
通讯作者：
Zhou TL
中科院分区：
文献类型：
--
作者：
Chen HL;Jiang Y;Li MM;Sun Y;Cao JM;Zhou C;Zhang XX;Qu Y;Zhou TL
替格环素是治疗耐碳青霉烯类肺炎克雷伯菌(CRKP)感染的最后手段。这项研究旨在扩大我们对CRKP获得侧支过敏性的理解，将其作为对替格环素产生耐药性的进化权衡。用替环素敏感的CRKP临床分离株进行替环素耐药的实验诱导。对这些临床分离株及其耐药后代进行药敏试验、微生物适合度评估、基因分型和全基因组测序。我们发现，CRKP临床分离株以逐渐增加的浓度暴露于替格环素后，成功地诱导了替格环素耐药性，而细菌细胞的适合性代价很小。定量逆转录聚合酶链式反应(RT-PCR)发现，耐药株外排泵基因AcrB及其调控基因RAMA的表达水平高于替格环素敏感株(5.3~64.5倍)和7.4~65.8倍(P<0.05)。耐药株对氨基糖苷类和其他抗生素有稳定的超敏反应，MIC显著降低(X~4-GT；500倍)。全基因组测序和质粒分析表明，诱导的伴随超敏反应可能是多方面的，抗菌素耐药(AMR)质粒的丢失可能是主要因素。这项研究使替吉环素和氨基糖苷类药物治疗CRKP感染的序贯联合治疗合理化。
Tigecycline is a last-resort antibiotic for infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). This study aimed to broaden our understanding of the acquisition of collateral hypersensitivity by CRKP, as an evolutionary trade-off of developing resistance to tigecycline. Experimental induction of tigecycline resistance was conducted with tigecycline-sensitive CRKP clinical isolates. Antimicrobial susceptibility testing, microbial fitness assessment, genotypic analysis and full-genome sequencing were carried out for these clinical isolates and their resistance-induced descendants. We found that tigecycline resistance was successfully induced after exposing CRKP clinical isolates to tigecycline at gradually increased concentrations, at a minor fitness cost of bacterial cells. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) found higher expression of the efflux pump gene acrB (5.3–64.5-fold) and its regulatory gene ramA (7.4–65.8-fold) in resistance-induced strains compared to that in the tigecycline-sensitive clinical isolates. Stable hypersensitivities to aminoglycosides and other antibiotics were noticed in resistance-induced strains, showing significantly lowered MICs (X 4 – >500 times). Full genome sequencing and plasmid analysis suggested the induced collateral hypersensitivity might be multifaceted, with the loss of an antimicrobial resistance (AMR) plasmid being a possible major player. This study rationalized the sequential combination of tigecycline with aminoglycosides for the treatment of CRKP infections.
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DOI：
10.1007/s10096-011-1481-x
发表时间：
2012-07
影响因子：
4.5
作者：
Sheng, J. -F.;Li, J. -J.;Tu, S.;Sheng, Z. -K.;Bi, S.;Zhu, M. -H.;Shen, X. -M.;Li, L. -J.
通讯作者：
Li, L. -J.
影响因子：
4.8
作者：
Frohlich, Christopher;Sorum, Vidar;Samuelsen, Orjan
通讯作者：
Samuelsen, Orjan
影响因子：
15.9
作者：
Pál C;Papp B;Lázár V
通讯作者：
Lázár V
影响因子：
4.9
作者：
Nielsen, Lindsey E.;Snesrud, Erik C.;Lesho, Emil P.
通讯作者：
Lesho, Emil P.
影响因子：
5.2
作者：
Dallenne, Caroline;Da Costa, Anaelle;Arlet, Guillaume
通讯作者：
Arlet, Guillaume