噬菌体介导的鲍曼不动杆菌对黏菌素的耐药性。

Phage-mediated colistin resistance in Acinetobacter baumannii.

机构信息

Department of Science, Roma Tre University, Viale G. Marconi 446, 00146 Rome, Italy; NBFC, National Biodiversity Future Center, piazza Marina 61, 90133 Palermo, Italy.

Department of Science, Roma Tre University, Viale G. Marconi 446, 00146 Rome, Italy; NBFC, National Biodiversity Future Center, piazza Marina 61, 90133 Palermo, Italy; Santa Lucia Foundation IRCCS, Via Ardeatina 306/354, 00179 Rome, Italy.

出版信息

Drug Resist Updat. 2024 Mar;73:101061. doi: 10.1016/j.drup.2024.101061. Epub 2024 Jan 28.

DOI:10.1016/j.drup.2024.101061

PMID:38301486

Abstract

AIMS

Antimicrobial resistance is a global threat to human health, and Acinetobacter baumannii is a paradigmatic example of how rapidly bacteria become resistant to clinically relevant antimicrobials. The emergence of multidrug-resistant A. baumannii strains has forced the revival of colistin as a last-resort drug, suddenly leading to the emergence of colistin resistance. We investigated the genetic and molecular basis of colistin resistance in A. baumannii, and the mechanisms implicated in its regulation and dissemination.

METHODS

Comparative genomic analysis was combined with genetic, biochemical, and phenotypic assays to characterize Φ19606, an A. baumannii temperate bacteriophage that carries a colistin resistance gene.

RESULTS

Ф19606 was detected in 41% of 523 A. baumannii complete genomes and demonstrated to act as a mobile vehicle of the colistin resistance gene eptA1, encoding a functional lipid A phosphoethanolamine transferase. The eptA1 gene is coregulated with its chromosomal homolog pmrC via the PmrAB two-component system and confers colistin resistance when induced by low calcium and magnesium levels. Resistance selection assays showed that the eptA1-harbouring phage Ф19606 promotes the emergence of spontaneous colistin-resistant mutants.

CONCLUSIONS

Φ19606 is an unprecedented example of a self-transmissible phage vector implicated in the dissemination of colistin resistance.

摘要

目的

抗菌药物耐药性是对人类健康的全球性威胁，鲍曼不动杆菌就是细菌对抗临床相关抗菌药物迅速产生耐药性的典型范例。多药耐药鲍曼不动杆菌菌株的出现迫使粘菌素重新作为最后手段的药物使用，这突然导致了粘菌素耐药性的出现。我们研究了鲍曼不动杆菌中粘菌素耐药的遗传和分子基础，以及其调控和传播所涉及的机制。

方法

通过比较基因组分析，结合遗传、生化和表型测定，对携带粘菌素耐药基因的鲍曼不动杆菌温和噬菌体 Ф19606 进行了表征。

结果

Ф19606 在 523 株鲍曼不动杆菌全基因组中的 41%中被检测到，被证明是携带编码功能性脂多糖磷酸乙醇胺转移酶的粘菌素耐药基因 eptA1 的移动载体。eptA1 基因与染色体同源物 pmrC 通过 PmrAB 双组分系统共同调控，并在低钙和镁水平诱导下赋予粘菌素耐药性。耐药性选择实验表明，携带 eptA1 的噬菌体 Ф19606 促进了自发产生粘菌素耐药突变体的出现。