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黏菌素耐药性的获得将细胞膜厚度改变与某基因中的一个点突变联系起来。

Acquisition of Colistin Resistance Links Cell Membrane Thickness Alteration with a Point Mutation in the Gene in .

作者信息

Saleh Neveen M, Hesham Marwa S, Amin Magdy A, Samir Mohamed Reham

机构信息

Department of Microbiology, Division of Basic Medical Science, National Organization for Drug Control and Research (NODCAR), Giza 12553, Egypt.

Department of Microbiology and Immunology, Faculty of Pharmacy, University of Cairo, Cairo 11562, Egypt.

出版信息

Antibiotics (Basel). 2020 Apr 6;9(4):164. doi: 10.3390/antibiotics9040164.

DOI:10.3390/antibiotics9040164
PMID:32268563
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7235794/
Abstract

is one of the most common causes of nosocomial infections in intensive care units. Its ability to acquire diverse mechanisms of resistance limits the therapeutic choices for its treatment. This especially concerns colistin, which has been reused recently as a last-resort drug against . Here, we explored the impact of gaining colistin resistance on the susceptibility of to other antibiotics and linked colistin resistance acquisition to a gene mutation in . The susceptibility of 95 isolates revealed that 89 isolates were multi-drug resistance (MDR), and nine isolates were resistant to colistin. Subsequently, three isolates, i.e., MS48, MS50, and MS64, exhibited different resistance patterns when colistin resistance was induced and gained resistance to almost all tested antibiotics. Upon TEM examination, morphological alterations were reported for all induced isolates and a colistin-resistant clinical isolate (MS34Col-R) compared to the parental sensitive strains. Finally, genetic alterations in and were assessed, and a point mutation in was identified in the MS64Col-R and MS34Col-R mutants, corresponding to Lys117Glu substitution in the lipid-binding domain. Our findings shed light on the implications of using colistin in the treatment of , especially at sub-minimum inhibitory concentrations concentrations, since cross-resistance to other classes of antibiotics may emerge, beside the rapid acquisition of resistance against colistin itself due to distinct genetic events.

摘要

是重症监护病房医院感染最常见的原因之一。其获得多种耐药机制的能力限制了治疗的选择。这尤其涉及到多粘菌素,它最近被重新用作对抗……的最后手段药物。在这里,我们探讨了获得多粘菌素耐药性对……对其他抗生素敏感性的影响,并将多粘菌素耐药性的获得与……中的基因突变联系起来。95株……分离株的药敏试验结果显示,89株为多重耐药(MDR),9株对多粘菌素耐药。随后,三株分离株,即MS48、MS50和MS64,在诱导多粘菌素耐药时表现出不同的耐药模式,并对几乎所有测试抗生素产生耐药性。经透射电镜检查,与亲本敏感菌株相比,所有诱导分离株和一株多粘菌素耐药临床分离株(MS34Col-R)均有形态学改变。最后,评估了……和……中的基因改变,在MS64Col-R和MS34Col-R突变体中鉴定出……中的一个点突变,对应于脂质结合结构域中的Lys117Glu替换。我们的研究结果揭示了使用多粘菌素治疗……的意义,特别是在低于最低抑菌浓度的情况下,因为除了由于独特的基因事件导致对多粘菌素本身的耐药性迅速获得外,还可能出现对其他类抗生素的交叉耐药。

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J Glob Antimicrob Resist. 2020 Jun;21:380-385. doi: 10.1016/j.jgar.2019.11.010. Epub 2019 Nov 23.
2
Multiple sequence types responsible for healthcare-associated Acinetobacter baumannii dissemination in a single centre in Egypt.多种序列类型导致埃及单一中心的医源性鲍曼不动杆菌传播。
BMC Infect Dis. 2019 Oct 7;19(1):829. doi: 10.1186/s12879-019-4433-1.
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Pathogens. 2024 Nov 28;13(12):1049. doi: 10.3390/pathogens13121049.
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Arch Microbiol. 2024 Mar 15;206(4):169. doi: 10.1007/s00203-024-03869-w.
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