关键词: Acinetobacter baumannii colistin resistant lipid A pmrAB

Mesh : Acinetobacter baumannii / genetics drug effects metabolism Humans Lipid A / genetics metabolism biosynthesis Bacterial Proteins / genetics metabolism Anti-Bacterial Agents / pharmacology Acinetobacter Infections / microbiology Microbial Sensitivity Tests Drug Resistance, Bacterial / genetics Polymyxins / pharmacology Colistin / pharmacology Transcription Factors / genetics metabolism Mutation

来  源:   DOI:10.1556/030.2024.02268

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:
在所有大陆,泛耐药鲍曼不动杆菌菌株的比率都在上升。这种细菌可以对所有抗生素产生抗药性,甚至粘菌素。在粘菌素抗性中,较早检测到了脂质A或/和两组分pmrAB的变化。我们调查并分析了从两名因感染性休克入院的重症监护病房患者中分离出的两株鲍曼不动杆菌(ABRC1和ABRC2)。两种菌株均对所有测试的抗生素具有抗性,包括MIC>256mgL-1的粘菌素。粘菌素抗性基因(pmrA,pmrB,lpxA,lpxC,lpxD,通过PCR和测序研究了两个菌株(ABRC1和ABRC2)的lpsB)。将获得的核酸序列与ATCC19606和17987的参考序列进行比对。在这项研究中,两个氨基酸突变,lpxC基因中的N287D和lpxD基因中的E117K,在ABRC1和ABRC2菌株中均检测到。ABRC1在pmrA基因中具有额外的H200L突变。两种粘菌素抗性菌株在pmrB基因中都具有相同的A138T突变。ABRC2菌株在激酶结构域中也有改变,特别是组氨酸激酶结构域的R263S取代。在两个鲍曼不动杆菌菌株的lpsB基因中发现了三个相同的突变:Q216K+H218G+S219E。因此,确定了ABRC1和ABRC2菌株中与ATCC17978和19606菌株中描述的不同的新推导的蛋白质序列。鲍曼不动杆菌的粘菌素抗性是多因素的。在我们的研究中,我们检测到粘菌素抗性鲍曼不动杆菌临床分离株中的新突变。
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