Effects of phage-based treatments against an OXA-48-producing Klebsiella pneumoniae isolate in simulated human gut microbiomes

Carbapenem-resistant K. pneumoniae (CRKP) is one of the most prevalent antimicrobial-resistant pathogens, primarily causing nosocomial infections. These bacteria often colonize the gut microbiota, and their carriage is an important risk factor for later infection. Phages are an emerging alternative against antimicrobial-resistant bacteria causing infections, but their effect on the microbiota is still poorly understood. Here, we simulated the colonization of the gut microbiota of three healthy adults by an OXA-48-producing CRKP isolate in a dynamic in vitro colonic simulator (SHIME®) and evaluated the effect of phage treatments in reducing CRKP load. Phage growth dynamics in the system seemed to be dependent on phage host range, rather than the donor’s microbiota composition. Additionally, phage treatment significantly reduced K. pneumoniae load and blaOXA-48 copy number, highlighting its potential for controlling the CRKP population. Importantly, phage treatment did not affect the microbiota diversity of any of the three donors, suggesting it has a minimal impact on the microbiome. Our results support the potential of phage-based strategies for the biocontrol of CRKP in the gut microbiota, reducing the abundance of this pathogen in its main reservoirs and preventing nosocomial CRKP infections.