Genomic characterization of novel lytic bacteriophages targeting carbapenemase producing multidrug resistant Klebsiella pneumoniae from Ethiopia: a molecular study.

Abstract

Klebsiella pneumoniae (K. pneumoniae) is a critical pathogen responsible for a wide range of severe infections. Its escalating resistance to frontline antimicrobials, particularly carbapenems, severely compromises existing therapeutic options and undermines current treatment strategies. This clinical challenge is further exacerbated by the emergence of multidrug-resistant (MDR) strains and hypervirulent lineages, which substantially complicate infection management and worsen patient outcomes. Ultimately, this alarming convergence of resistance and virulence presents a severe public health threat that necessitates the urgent development of novel therapeutic approaches; in this regard, phage therapy is emerging as a promising strategy. Bacteriophages and their derivatives have garnered increasing recognition as targeted antibacterial agents, demonstrating potent activity against carbapenemase producing and MDR K. pneumoniae in vitro models. They effectively lyse MDR strains, disrupt biofilm formation, and have shown promising therapeutic efficacy across various in vivo models. To ensure safety in clinical applications, genome sequencing is essential to identify and exclude undesirable genes, thereby determining therapeutic suitability. Here, we have sequenced and analyzed the genomic characteristics of seven lytic bacteriophages targeting carbapenemase-producing MDR K. pneumoniae. Genomic evaluation confirmed that these phages are strictly lytic and revealed the presence of distinct lysis modules across the genomes. Phylogenetic analysis showed that these phages cluster within four genera of Caudoviricetes: Taipeivirus, Drulisvirus, Przondovirus, and Webervirus. The phage genomes ranged from 15,773 to 166,437 base pairs (bp) in length and encoded core structural and replication modules. Furthermore, distinct lytic modules predicted to have function in bacterial capsule degradation were identified across the genomes. Importantly, the absence of known virulence or toxin genes guarantees therapeutic safety and satisfies rigorous genomic criteria for clinical translation. These findings underscore the potential of these phages as a promising alternative for combating MDR and hypervirulent K. pneumoniae infections. Future in vivo investigations and clinical trials are essential to validate their therapeutic efficacy, safety profile, and optimal treatment protocols.