Identification of KL29 type acinetobacter baumannii phage of obolenskvirus subfamily and tail-associated depolymerase...

The emergence of multidrug-resistant Acinetobacter baumannii (MDR-AB) as a critical nosocomial pathogen, driven by its remarkable capacity for acquired antibiotic resistance and clonal dissemination, underscores an urgent need for novel therapeutic interventions. This study characterizes a novel depolymerase derived from bacteriophage vB_AbaM_IME284, previously isolated against Ab333. Genomic analysis revealed taxonomic classification within the Caudoviricetes class and Obolenskvirus subfamily. Notably, plaque halo formation indicated polysaccharide depolymerase activity, prompting functional investigation of ORF49-encoded protein (designated Dp49). Recombinant Dp49 exhibited both depolymerase and antibacterial activities, demonstrating efficacy in biofilm inhibition and eradication. Furthermore, synergistic bactericidal effects were observed when combining Dp49 with human serum components (6-log reduction in viable counts). These findings position Dp49 as a promising therapeutic candidate for combating biofilm-associated MDR-AB infections. As a priority pathogen listed by the WHO, A. baumannii poses formidable challenges in clinical management through its rapid acquisition of multidrug resistance mechanisms and notorious capacity for forming recalcitrant biofilms that severely compromise conventional antimicrobial interventions. Our study characterizes Dp49, a newly discovered bacteriophage-derived depolymerase exhibiting potent enzymatic activity against bacterial exopolysaccharides. This enzyme demonstrates therapeutic potential by enhancing serum-mediated bactericidal activity and anti-biofilm activity. These findings not only expand the therapeutic arsenal against pan-drug resistant Gram-negative pathogens but also provide crucial mechanistic insights into phage enzyme applications. The demonstrated biofilm-disrupting capacity of Dp49 underscores the evolving paradigm of phage-derived biologics as precision anti-infectives, representing a strategic imperative in antimicrobial research given the critical void in effective therapies for extensively drug-resistant infections.