Cooperative Bacterial Interactions Mediate Resistance To Colonization By Intestinal Pathogens

Abstract

The diverse microbial populations constituting the intestinal microbiota promote immune development, nutrient digestion and colonization resistance against invading pathogens. Due to their complex metabolic requirements and the consequent difficulty culturing them, they remained, until recently, largely uncharacterized. In the past decade, deep nucleic acid sequencing platforms, new computational and bioinformatics tools and full genome characterization of several hundred commensal bacterial species have facilitated studies of the microbiota and revealed that differences in microbiota composition can be associated with a myriad of conditions and that the microbiota can be manipulated to prevent, reduce and even cure some of them. One of the most critical functions of the microbiota is to prevent the expansion of disease- causing organisms. Different bacterial species exert different roles within the intestine and therefore, the composition of the microbiota determines, in part, the level of resistance to infection. Perturbation of microbial communities with antibiotics renders the host susceptible to colonization by opportunistic antibiotic-resistant bacteria. The studies discussed in this dissertation aim to determine the impact that vancomycin-resistant Enterococcus (VRE) and carbapenem-resistant Klebsiella pneumoniae, two common hospital-acquired infections, have on each other and on the host and to identify intestinal bacteria responsible for colonization resistance against VRE. We demonstrate that VRE and K. pneumoniae coexist within the intestine despite residing in very close proximity to each other and that colonization resistance against VRE can be mediated by two bacterial species despite antibiotic treatment. This work highlights the complex interplay between gut bacteria and has important implications for the development of new therapeutics to treat intestinal infections.