Development of expanded host range phage active on biofilms of multi-drug resistant Pseudomonas aeruginosa

Area of Science:

• Microbiology and Virology
• Bacteriophage Research
• Antimicrobial Resistance

Background:

• Phage therapy is a potential treatment for multi-drug resistant (MDR) bacterial infections.
• A major limitation of phage therapy is the narrow host range of individual phages.
• Expanding phage host range is crucial for effective treatment of diverse bacterial strains.

Purpose of the Study:

• To develop and evaluate a host range expansion (HRE) protocol for Pseudomonas aeruginosa phages.
• To create phage cocktails with broad and predictable host ranges.
• To assess the anti-biofilm activity and therapeutic efficacy of expanded-host-range phages.

Main Methods:

• A host range expansion (HRE) protocol involving co-incubation of phages with multiple P. aeruginosa strains was developed.
• The protocol was applied to a mixture of four phages using sixteen P. aeruginosa strains.
• Individual phage clones and reconstituted phage cocktails were characterized for host range and anti-biofilm activity.

Main Results:

• The HRE protocol generated undefined phage mixtures with significantly expanded host ranges.
• Defined phage cocktails, reconstituted from host range-characterized clones, demonstrated predictable and broad lytic activity.
• Phage preparations showed dose-dependent inhibition of biofilm formation and reduction of existing biofilms, outperforming levofloxacin in a resistant strain.

Conclusions:

• The HRE protocol is a rapid method for generating phage libraries with expanded host ranges.
• This approach enables the creation of defined phage cocktails with predictable efficacy against P. aeruginosa.
• The developed phages exhibit significant anti-biofilm activity and therapeutic potential against MDR P. aeruginosa infections.