Bacteriophage-induced outer membrane protein remodelling drives the phenotypic switching and antibiotic re-sensitization in Klebsiella pneumoniae.

AIM: Bacteriophages are the most common biological agents that target bacteria, offering a potential alternative to antibiotics for treating multidrug-resistant pathogens, such as Klebsiella pneumoniae. The onset of bacteriophage resistance remains a significant obstacle. This study highlights the role of outer membrane proteins (OMPs) in the development of bacteriophage resistance in K. pneumoniae.

METHOD: The study examined the native OMP profiles of isolates that are sensitive and resistant to bacteriophages. K. pneumoniae isolates were treated with bacteriophages, and the survivors were subcultured to generate bacteriophage-tolerant strains. These strains were further characterised phenotypically, and OMP encoding gene expression was studied using quantitative real-time PCR.

RESULTS

OMP encoding genes were significantly upregulated, and OMPs were overexpressed in these tolerant strains. Bacteriophage-tolerant strains exhibited increased resistance to other phages, lower growth rates, enhanced biofilm-forming abilities, and reduced capsule production. The bacteriophage-tolerant strains also showed susceptibility to antibiotics to which the parent strains had earlier displayed resistance, particularly to carbapenems and macrolides.

CONCLUSION

Understanding the mechanisms of phage emergence can help us prepare for and mitigate the threat of unprecedented phage resistance, which could pose a significant public health risk.