Therapeutic potential of Shigella phage SSG23 against Shigella sonnei biofilms and in BALB/c mice

Multidrug-resistant (MDR) Shigella spp. threaten global health, renewing interest in phage therapy. Here, we report the isolation and characterization of a novel lytic phage, SSG23, effective against four major Shigella serovars. Phage SSG23 possesses a prolate head and contractile tail, consistent with the Straboviridae family, and remains stable across a broad pH (4-11) and temperature range (-20 °C to 50 °C). It exhibits a latent period of 37 minutes, a burst size of 195 plaque-forming units per cell, and a 168,820 bp dsDNA genome with 40.8% GC content lacking resistance or toxin genes. SSG23 efficiently degrades biofilms, alone or with antibiotics, and is non-toxic to macrophages in vitro. In S. sonnei-infected BALB/c mice, oral administration reduced bacterial colonization and shedding while improving health without evidence of resistance emergence. Neutralizing antibodies developed in mice, yet the phage maintained its efficacy. These findings support SSG23 as a promising candidate for phage therapy against Shigella infection.