Phage resistance profiles of AB-phages treated Acinetobacter baumannii: implications for phage therapy strategies.

INTRODUCTION

Phage therapy is a promising alternative for combating multidrug-resistant bacteria, including Acinetobacter baumannii (AB). However, the development of phage-resistant variants after treatment, particularly when using phage cocktails, poses a significant challenge. This resistance can hinder the effectiveness of future phage-based treatments against pathogenic AB.

METHODOLOGY: Three AB-specific phages-AB-phage 22, AB-phage 27, and AB-phage 32-susceptible to an AB isolate, designated ABU-3, were used as a model to study phage resistance development in AB following phage treatment. This study proposes a strategy to effectively eliminate pathogenic AB using an optimal multiplicity of infection (MOI), referred to as the MOI clearance value.

RESULTS

The MOI clearance values required for complete elimination of ABU-3 were determined to be 10 for AB-phages 22 and 32 and 100 for AB-phage 27. Surviving ABU-3 colonies from lower MOI treatments were analyzed for phage resistance. ABU-3 treated with AB-phage 27 developed resistance to AB-phage 27 but remained susceptible to AB-phages 22 and 32. ABU-3 treated with AB-phage 22 developed resistance to AB-phage 22 but retained partial susceptibility to the other phages at reduced MOI. In contrast, ABU-3 treated with AB-phage 32 displayed complete resistance to all three phages.

CONCLUSIONS

These findings highlight a key challenge in phage therapy: insufficient MOI ratio can promote phage resistance. The distinct resistance profiles observed emphasize the importance of optimizing phage combinations and dosages to prevent resistance development during treatment.