Competition in the gut: From ecology to novel therapeutics
Helmholtz Center for Infection Research, Microbial Immune Regulation, Braunschweig, Germany
Healthcare-associated infections especially those caused by Gram-negative multidrug-resistant organisms (GN-MDR) are a leading cause of morbidity and mortality worldwide. Gut colonization with these GN-MDRs often precedes systemic infections in patients. Decolonization strategies based on treatments with antibiotics have a long-lasting and broad impact on the gut microbiota and put further selective pressure towards the development of multi- and pan-resistance of nosocomial pathogens. Therefore, alternative methods are urgently required to eliminate selectively MDR pathogens.
In my laboratory we aim to develop “live biotherapeutic drugs” (LBP) as novel therapeutics against GN-MDR selectively targeting the pathogen while leaving the surrounding microbiota intact. Our approach is based on ecological principles, namely nutrient competition between related bacteria. Utilizing ex vivo assays and large strain collections of commensal bacteria, we identified in the past years that the commensal bacteria Klebsiella oxytoca promotes colonization resistance against various GN-MDR and enteropathogens in the gut. In two instances we have linked the phenotype to competition for different nutrients in vivo. Moreover, the microbial context of the competition, i.e., the presence of additional commensal bacteria, plays an important role in the process of decolonization in line with the current understanding of gut microbiota ecology.