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多黏菌素耐药鲍曼不动杆菌分离株中 pmrAB 双组分系统和脂 A 生物合成基因的遗传改变。

Genetic alterations in the pmrAB two-component system and lipid A biosynthesis genes of polymyxin-resistant Acinetobacter baumannii isolates.

机构信息

1Research Team of Epidemiology and Bacterial Resistance, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Rabat, Morocco.

2Department of Clinical Bacteriology, Mohammed V Military Teaching Hospital, Rabat, Morocco.

出版信息

Acta Microbiol Immunol Hung. 2024 Jun 5;71(2):134-139. doi: 10.1556/030.2024.02268. Print 2024 Jul 2.

DOI:10.1556/030.2024.02268
PMID:38837239
Abstract

The rate of pandrug-resistant Acinetobacter baumannii strains is on the rise in all continents. This bacterium can acquire resistance to all antibiotics, even to colistin. Alterations in the lipid A or/and the two-component pmrAB were earlier detected in colistin resistance. We investigated and analyzed two strains of A. baumannii (ABRC1 and ABRC2) isolated from two patients admitted to intensive care unit with a septic shock. Both strains were resistant to all tested antibiotics including colistin with a MIC >256 mg L-1. Colistin resistance genes (pmrA, pmrB, lpxA, lpxC, lpxD, and lpsB) of two strains (ABRC1 and ABRC2) were investigated by PCR and sequencing. Obtained nucleic acid sequences were aligned with reference sequences of ATCC 19606 and 17987. In this study two amino acid mutations, N287D in the lpxC gene and E117K in the lpxD gene, were detected in both ABRC1 and ABRC2 strains. ABRC1 had an additional H200L mutation in the pmrA gene. Both colistin resistant strains harbored the same A138T mutation in the pmrB gene. The ABRC2 strain also had an alteration in the kinase domain, specifically an R263S substitution of the histidine kinase domain. Three identical mutations were found in the lpsB gene of both A. baumannii strains: Q216K + H218G + S219E. As a result, a newly deduced protein sequence in both ABRC1 and ABRC2 strains differed from those described in ATCC 17978 and 19606 strains was determined. Colistin resistance is multifactorial in A. baumannii. In our study we detected novel mutations in colistin resistant A. baumannii clinical isolates.

摘要

所有大陆的泛耐药鲍曼不动杆菌菌株的发生率都在上升。这种细菌可以获得对所有抗生素的耐药性,甚至对多粘菌素。以前在多粘菌素耐药性中检测到脂 A 或/和双组分 pmrAB 的改变。我们调查并分析了从两名入住重症监护病房并发感染性休克的患者中分离出的两种鲍曼不动杆菌(ABRC1 和 ABRC2)菌株。这两种菌株均对所有测试的抗生素(包括 MIC>256mg/L 的多粘菌素)均具有耐药性。通过 PCR 和测序研究了两种菌株(ABRC1 和 ABRC2)的多粘菌素耐药基因(pmrA、pmrB、lpxA、lpxC、lpxD 和 lpsB)。获得的核酸序列与 ATCC 19606 和 17987 的参考序列进行比对。在这项研究中,在 ABRC1 和 ABRC2 菌株中均检测到 lpxC 基因中的 N287D 和 lpxD 基因中的 E117K 两个氨基酸突变。ABRC1 在 pmrA 基因中还有一个额外的 H200L 突变。两种多粘菌素耐药菌株均在 pmrB 基因中具有相同的 A138T 突变。ABRC2 菌株在组氨酸激酶结构域中还存在 R263S 取代的激酶结构域改变。两种鲍曼不动杆菌菌株的 lpsB 基因均发现了三个相同的突变:Q216K+H218G+S219E。结果,在 ABRC1 和 ABRC2 两种菌株中,新推断的蛋白质序列与 ATCC 17978 和 19606 菌株中描述的序列不同。鲍曼不动杆菌的多粘菌素耐药性是多因素的。在我们的研究中,我们检测到了耐多粘菌素鲍曼不动杆菌临床分离株的新突变。

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