Work

The therapeutic potential of phage pT2784 against ST40-KL47 type Acinetobacter baumannii and bacterial fitness trade-offs

Year: 2026

Type: article

Abstract: ABSTRACT Acinetobacter baumannii usually causes high-mortality infections as the World Health Organization’s priority pathogen. Herein, we isolated a novel lytic phage pT2784 from hospital wastewater, specifically targeting the emerging Acinetobacter baumannii ST40-KL47 lineage and demonstrated significant antibacterial effects in in vitro and in vivo models. Morphological analysis showed that pT2784 is a myovirus with a head diameter of 54.53 ± 0.27 nm and a tail length of 71.96 ± 0.87 nm. Genomic analysis revealed that pT2784 possessed a 44,335 bp DNA genome with low identity (≤61%) to known phages, supporting its classification into a new genus within Caudoviricetes class. Phage pT2784 displayed an optimal multiplicity of infection of 0.01, a short latent period of approximately 5 min, and a burst size of 193 plaque-forming units (PFU)/cell. It maintained high stability over a broad temperature range (4°C–65°C) and pH range (2–11). Phage-resistant strains were isolated and purified following 24-h co-culture. Whole-genome sequencing identified missense mutations in itrA3 and gtr50 , which encoded key enzymes involved in the early-stage pathway of capsule polysaccharide synthesis. Phenotypic analysis confirmed that phage-resistant strains exhibited capsule thinning, impaired phage adsorption, significantly reduced biofilm formation, and attenuated virulence, evidenced by over 80% survival in Galleria mellonella at 72 h, while none survived in the wild-type group by 12 h. Collectively, this study not only presented pT2784 as a promising therapeutic candidate but also elucidated the mechanism by which evolution under phage pressure promoted attenuated virulence in exchange for resistance, offering a crucial theoretical basis for developing phage-based interventions against Acinetobacter baumannii . IMPORTANCE The rise of antibiotic-resistant Acinetobacter baumannii is a critical global health threat, urgently demanding new treatments. This study introduced a newly discovered phage, pT2784, which exhibited potent and specific lytic activity against Acinetobacter baumannii ST40-KL47. Crucially, we demonstrated that upon the emergence of phage resistance, the bacteria concurrently underwent a significant attenuation of their pathogenic potential. This work not only provided a promising new candidate for phage therapy but also revealed a fundamental trade-off where the path to phage resistance leads to attenuated bacterial virulence, offering a strategic advantage for managing challenging Acinetobacter baumannii infections.

Source: Microbiology Spectrum

DOI: 10.1128/spectrum.03301-25