The Basis for Natural Multiresistance to Phage in Pseudomonas aeruginosa

Area of Science:

• Microbiology
• Genomics
• Bacteriology

Background:

• Pseudomonas aeruginosa causes persistent infections and is challenging to treat, especially within biofilms.
• Phage therapy is a potential alternative to antibiotics, but some clinical strains exhibit resistance to multiple phages.

Purpose of the Study:

• To characterize phage-resistant Pseudomonas aeruginosa clinical strains and compare them with susceptible strains.
• To understand the genetic and phenotypic basis of multi-phage resistance in P. aeruginosa.

Main Methods:

• Phenotypic characterization of phage-resistant and susceptible P. aeruginosa strains.
• Whole-genome sequencing of three phage-resistant strains.
• Analysis of mutations in genes related to lipopolysaccharide (LPS) and type IV pilus synthesis.

Main Results:

• Phage-resistant strains showed defects in LPS biosynthesis, were nonmotile, and exhibited high autolysis.
• Genome sequencing revealed accessory genomes with insertion elements, genomic islands, pyocins, and prophages, including those performing lateral transduction.
• Mutations were identified in genes crucial for LPS and/or type IV pilus synthesis, the primary phage receptors.
• CRISPR-Cas systems were absent or inactive in resistant strains, indicating they do not confer resistance to lytic phages.

Conclusions:

• Multiphage-resistant P. aeruginosa strains possess distinct genetic profiles and phenotypic traits, including LPS defects and altered motility.
• These resistant strains exhibit selective advantages, utilizing mechanisms like pyocin production to eliminate competing bacteria.
• Understanding these resistance mechanisms is crucial for developing effective phage therapy strategies against P. aeruginosa infections.