PT  - JOURNAL ARTICLE
AU  - Wang, Xiaoqing
AU  - Loh, Belinda
AU  - Yu, Yunsong
AU  - Hua, Xiaoting
AU  - Leptihn, Sebastian
TI  - Phage Resistance Mechanisms Increase Colistin Sensitivity in <em>Acinetobacter baumannii</em>
AID  - 10.1101/2021.07.23.453473
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.07.23.453473
4099  - http://biorxiv.org/content/early/2021/07/23/2021.07.23.453473.short
4100  - http://biorxiv.org/content/early/2021/07/23/2021.07.23.453473.full
AB  - Few emergency-use antibiotics remain for the treatment of multidrug-resistant bacterial infections. Infections with resistant bacteria are becoming increasingly common. Phage therapy has reemerged as a promising strategy to treat such infections, as microbial viruses are not affected by bacterial resistance to antimicrobial compounds. However, phage therapy is impeded by rapid emergence of phage-resistant bacteria during therapy. In this work, we studied phage-resistance of colistin sensitive and resistant A. baumannii strains. Using whole genome sequencing, we determined that phage resistant strains displayed mutations in genes that alter the architecture of the bacterial envelope. In contrast to previous studies where phage-escape mutants showed decreased binding of phages to the bacterial envelope, we obtained several not uninfectable isolates that allowed similar phage adsorption compared to the susceptible strain. When phage-resistant bacteria emerged in the absence of antibiotics, we observed that the colistin resistance levels often decreased, while the antibiotic resistance mechanism per se remained unaltered. In particular the two mutated genes that conveyed phage resistance, a putative amylovoran-biosynthesis and a lipo-oligosaccharide (LOS) biosynthesis gene, impact colistin resistance as the mutations increased sensitivity to the antibiotic.Competing Interest StatementThe authors have declared no competing interest.