Compounding Achromobacter Phages for Therapeutic Applications.

Area of Science:

• Microbiology
• Virology
• Genomics

Background:

• Achromobacter species are increasingly identified as problematic respiratory pathogens in Cystic Fibrosis (CF) patients.
• These bacteria exhibit natural resistance to multiple antibiotics, limiting treatment options.
• Fatal exacerbations have been linked to Achromobacter colonization in CF airways.

Purpose of the Study:

• To isolate and characterize lytic bacteriophages for potential therapeutic use against Achromobacter species.
• To establish a comprehensive framework for phage isolation, genomic analysis, and safe production for phage therapy.

Main Methods:

• Isolation and morphological/genomic characterization of thirteen novel lytic phages, forming the Achromobacter Kumeyaay phage collection.
• Phylogenetic analysis to identify six distinct Achromobacter phage genome clusters.
• Infectivity testing against 23 clinical Achromobacter isolates.
• Characterization of an induced cryptic prophage (Achromobacter phage CF418-P1).
• Large-scale phage production with endotoxin removal via an octanol-based procedure.

Main Results:

• The Achromobacter Kumeyaay phage collection comprises thirteen lytic phages.
• Phylogenetic analysis revealed six distinct Achromobacter phage genome clusters.
• 78% of tested clinical Achromobacter isolates were susceptible to lysis by at least one phage.
• A cryptic prophage, Achromobacter phage CF418-P1, was identified and characterized.
• Safe, large-scale phage production achieved a concentration of 1 × 10^9 PFU/mL with endotoxin levels below FDA recommendations.

Conclusions:

• Lytic phages represent a viable therapeutic strategy for managing Achromobacter infections in Cystic Fibrosis.
• The characterized phage collection and production methods provide a foundation for developing phage therapy interventions.
• Further research is needed on prophage induction during phage therapy preparation.