Colistin-phage combinations decrease antibiotic resistance in Acinetobacter baumannii via changes in envelope...

Area of Science:

• Microbiology
• Bacteriology
• Genetics

Background:

• Multidrug-resistant bacterial infections pose a significant global health threat.
• Phage therapy is a promising alternative to antibiotics, but bacterial resistance to phages is a challenge.
• Acinetobacter baumannii is a critical priority pathogen with limited treatment options.

Purpose of the Study:

• To elucidate the mechanisms of phage resistance in Acinetobacter baumannii.
• To characterize a novel phage, Phab24, and its interaction with A. baumannii.
• To assess the impact of phage resistance on bacterial virulence and antibiotic sensitivity.

Main Methods:

• Isolation and characterization of a novel phage (Phab24) targeting Acinetobacter baumannii.
• Generation and whole-genome sequencing of phage-resistant A. baumannii mutants.
• Phenotypic characterization including virulence assays in Galleria mellonella and antibiotic sensitivity testing.

Main Results:

• Phage-resistant A. baumannii strains exhibited mutations affecting the bacterial capsule and outer membrane.
• Phage Phab24 utilizes the bacterial capsule as its primary receptor.
• Phage-resistant isolates displayed reduced virulence and, notably, increased sensitivity to colistin.

Conclusions:

• Phage resistance in A. baumannii is mediated by alterations in the bacterial envelope structure.
• The emergence of phage resistance can unexpectedly re-sensitize bacteria to antibiotics like colistin.
• This phage-induced antibiotic hypersensitivity presents a potential strategy for combating multidrug-resistant infections.