Characterization of phage AbpL with a terminally redundant genome and its therapeutic potential against drug-resistantinfections.

Abstract

INTRODUCTION: The growing global threat of multidrug-resistant(MDR-AB) infections highlights an urgent need for novel and effective therapeutic strategies. Phage therapy has emerged as a promising alternative to conventional antibiotics. This study aimed to isolate and comprehensively characterize a novel lytic bacteriophage (phage), designated AbpL, and evaluate its therapeutic potential against MDR-AB. METHODS: AbpL was isolated from sewage samples and characterized in terms of its morphology, growth characteristics, stability, and genome. Comparative genomic classification analysis was also conducted on it.efficacy was evaluated through time-kill assays and biofilm disruption experiments. To assesstherapeutic potential, a murine model of lethal-induced sepsis was employed, with outcomes including survival rates, bacterial burden, serum levels of inflammatory cytokines, and histopathological evaluation. RESULTS: AbpL is classified as a member of the genus, subfamily, family, order, and class. It exhibited an icosahedral head and a short non-contractile tail, and demonstrated a short latent period, a high burst size, and strong stability across a broad range of environmental conditions. AbpL showed lytic activity against 52% of clinical MDR-AB isolates and effectively disrupted pre-existing biofilms. In the murine sepsis model, a single intraperitoneal administration (multiplicity of infection = 10) conferred 100% survival, significantly reduced bacterial loads in the liver and kidneys, and attenuated systemic inflammation compared to treatment with polymyxin B. Histopathological analyses further confirmed the protective effects of AbpL and its favorable safety profile. DISCUSSION: Owing to its strong lytic activity, environmental stability, and robustandefficacy, AbpL represents a highly promising candidate for the treatment of MDR-AB infections. Furthermore, its unique 400-bp terminal redundancy may serve as a valuable platform for future engineering via synthetic biology approaches.