New phage holds promise for treating drug-resistant bacterial infections

Burkholderia cepacia complex (Bcc) infections are a serious concern for cystic fibrosis (CF) patients, often leading to the need for lung transplants. On March 16, researchers from Texas A&M developed a versatile phage called Milagro vir gp20:Milo Δcl from Milagro to combat multiple drug-resistant Bcc species, and they've also created a CRISPR/Cas9 system for direct gene editing of virulent phages.

The research highlights Bcc, which poses a life-threatening risk to CF patients, often necessitating lung transplantation. Unfortunately, pre-transplant colonization by antibiotic-resistant Bcc strains is linked to poor post-transplant outcomes. To combat this issue, phage therapy has emerged as a potential solution for drug-resistant bacterial infections. However, most known Bcc phages are temperate, rendering them unsuitable for phage therapy, and the few virulent phages discovered have limited host ranges.

According to the report, in order to address these limitations, researchers have engineered a virulent, broad-host range phage called Milagro vir gp20:Milo Δcl, derived from the temperate phage Milagro. This engineered phage incorporates specific mutations, including alterations in the lysogenic repressor binding site, deletion of the lysogenic repressor gene and a fusion of the phage tail fiber with the receptor-binding domain of the broad-host-range tailocin BceTMilo (bacteriocin).         

Consequently, the report said, Phage Milagro vir gp20:Milo Δcl exhibits a significantly expanded host range, capable of infecting multiple Bcc species, including B. cenocepacia, B. multivorans, B. gladioli and B. vietnamensis. To facilitate ongoing phage engineering endeavors, researchers have also developed a CRISPR/Cas9 system in Burkholderia, allowing for direct gene editing of virulent phages.        

Research Square: Guichun Yao, et al. Engineering of the temperate Burkholderia phage Milagro for use as a therapeutic. Research Square (16 March 2023). https://doi.org/10.21203/rs.3.rs-2626327/v1