The role of microbiota blooming in the horizontal spread of antibiotic resistance

Carbapenemase-producing Enterobacteriaceae (CPE) are critical priority antibiotic-resistant pathogens that pose a major threat to public health and are associated with up to 20% mortality rates. Plasmid-encoded carbapenemases frequently spread via conjugation between Enterobacteriaceae species within the intestine of colonised patients, but we currently understand little about the fundamental mechanisms driving this dissemination and lack strategies to prevent it. Under normal conditions Enterobacteriaceae are vastly outnumbered by commensal anaerobes within the gastrointestinal tract and the physical contact between donor and recipient bacteria required for conjugative transfer is limited. Antibiotic treatment can lead to ‘blooms’ of otherwise low-abundance Enterobacteriaceae, increasing the encounter rate between CPE and potential recipient bacteria. The collateral effects of antibiotics on the composition and spatial biogeography of the microbiota may therefore play an essential role in facilitating the horizonal spread of carbapenem resistance. Leveraging an interdisciplinary approach, I will deconvolve mechanisms by which antibiotic-induced enterobacterial blooms foster the conjugative spread of carbapenem resistance within the intestinal microbiota. I will determine how the microbiota community structure affects this dissemination in order to identify potential interventions and how the spread of resistance influences microbiota recovery. Keywords: Antibiotics, Antimicrobial Resistance, Horizontal Gene Transfer, Microbiome