Phage-mediated colistin resistance in Acinetobacter baumannii

• Published in: Drug resistance updates 2024-03, Vol.73, p.101061-101061, Article 101061
• Main Authors: Lucidi, Massimiliano, Imperi, Francesco, Artuso, Irene, Capecchi, Giulia, Spagnoli, Cinzia, Visaggio, Daniela, Rampioni, Giordano, Leoni, Livia, Visca, Paolo
• Format: Article
• Language: English
• Subjects: Acinetobacter baumannii; Colistin resistance; eptA1; Phage; Phosphoethanolamination; Φ19606
• ISSN: 1368-7646; 1532-2084
• DOI: 10.1016/j.drup.2024.101061

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. 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. 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. Φ19606 is an unprecedented example of a self-transmissible phage vector implicated in the dissemination of colistin resistance. •Φ19606 is an Acinetobacter baumannii temperate phage carrying the eptA1 gene.•EptA1 is a lipid A phosphoethanolamine transferase conferring colistin resistance.•Φ19606 mediates transmission of the eptA1 colistin resistance gene in A. baumannii.•eptA1 is induced by the PmrAB two-component system at low levels of Ca2+ and Mg2+.•Φ19606 promotes the emergence of colistin-resistant mutants.