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Phage-mediated colistin resistance in Acinetobacter baumannii
Drug Resistance Updates ( IF 24.3 ) Pub Date : 2024-01-28 , DOI: 10.1016/j.drup.2024.101061
Massimiliano Lucidi , Francesco Imperi , Irene Artuso , Giulia Capecchi , Cinzia Spagnoli , Daniela Visaggio , Giordano Rampioni , Livia Leoni , Paolo Visca

Antimicrobial resistance is a global threat to human health, and is a paradigmatic example of how rapidly bacteria become resistant to clinically relevant antimicrobials. The emergence of multidrug-resistant . 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 , and the mechanisms implicated in its regulation and dissemination. Comparative genomic analysis was combined with genetic, biochemical, and phenotypic assays to characterize Φ19606, an . temperate bacteriophage that carries a colistin resistance gene. Ф19606 was detected in 41% of 523 . complete genomes and demonstrated to act as a mobile vehicle of the colistin resistance gene , encoding a functional lipid A phosphoethanolamine transferase The gene is coregulated with its chromosomal homolog via the PmrAB two-component system and confers colistin resistance when induced by low calcium and magnesium levels. Resistance selection assays showed that the -harbouring phage Ф19606 promotes the emergence of spontaneous colistin-resistant mutants. Φ19606 is an unprecedented example of a self-transmissible phage vector implicated in the dissemination of colistin resistance.

中文翻译:

鲍曼不动杆菌噬菌体介导的粘菌素耐药性

抗菌药物耐药性是对人类健康的全球性威胁,也是细菌对临床相关抗菌药物产生耐药性的典型例子。多重耐药性的出现。菌株迫使粘菌素作为最后手段重新流行,突然导致粘菌素耐药性的出现。我们研究了粘菌素耐药性的遗传和分子基础,以及与其调节和传播有关的机制。比较基因组分析与遗传、生化和表型测定相结合,以表征 Φ19606,一种 . 携带粘菌素抗性基因的温带噬菌体。Ф19606 在 523 份中的 41% 中被检测到。完整的基因组,并被证明可作为粘菌素抗性基因的移动载体,编码功能性脂质 A 磷酸乙醇胺转移酶 该基因通过 PmrAB 双组分系统与其染色体同源物共同调节,并在低钙和镁水平诱导时赋予粘菌素抗性。抗性选择试验表明,携带噬菌体Ф19606 促进了自发的粘菌素抗性突变体的出现。Φ19606 是一个前所未有的自传播噬菌体载体的例子,与粘菌素耐药性的传播有关。
更新日期:2024-01-28
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