Phage Digestion of a Bacterial Capsule Imparts Resistance to Two Antibiotic Agents

Abstract

Bacteriophages are viruses that infect bacteria, replicating and multiplying using host resources. For specific infections, bacteriophages have developed extraordinary proteins for recognizing and degrading their host. Inspired by the remarkable development of viral proteins, we used the tail fiber protein to treat multiple drug-resistant Acinetobacter baumannii. The tail fiber protein exhibits polysaccharide depolymerases activity which specifically degrades exopolysaccharide (EPS) during the phage–host interaction. However, EPS-degraded cells are observed altering host susceptibility to bacterial lysis peptide, the endolysin-derived peptide. Notably, endolysin is necessary in the process of progeny liberation by breaking the bacterial cell wall. Surprisingly, peeling the EPS animated host to resist colistin, the last-resort antibiotic used in multidrug-resistant Gram-negative bacteria infection. Tail fiber-modified cell wall reduces colistin attachment, causing temporary antibiotic-resistance and possibly raising clinical risks in treating multiple drug-resistant A. baumannii.

The Structure and Function of Biomaterial Endolysin EFm1 from E. faecalis Phage

“…EFm1 and EFm1 D166Q could lyse 22 clinical strains, except E. faecalis 945. We hypothesized that E. faecalis 945 may possess a unique capsule or biofilm or a hydrolase on the outer cell wall, helping it escape or resist the activity of EFm1, or absent tail fiber protein of phage which specifically degrades biofilm during the phage host interaction [ 31 ]. These implied that E. faecalis 945 might be the most suitable bacteria used to further investigate the resistance mechanisms of endolysins and the emergence of endolysin-resistant E. faecalis might bring new challenge for phage therapy.…”

Potential of phage depolymerase for the treatment of bacterial biofilms

“…Nevertheless, the combination of phage depolymerase and colistin may not produce a synergistic effect. Luo et al [ 112 ]. identified another A. baumannii phage depolymerase called TF, which did not exhibit any additive or synergistic effects with colistin on the host bacteria.…”