Evolution of Antibiotic-Resistance Mechanisms

Project PI: Daniel Schultz, PhD

Bacteria are able to withstand very large doses of antibiotics through the acquisition of dedicated resistance mechanisms that inactivate the drug, alter the drug target, or reduce membrane permeability to the drug. Antibiotic resistance (AR) has emerged as one of the most urgent threats to public health, affecting over 2 million infections yearly in the USA. In recent decades, AR has started to outpace our efforts to find new drugs; however, producing and resisting antimicrobial compounds has been part of bacterial life for over a billion years, mostly in the soil. In order to halt the spread of AR across bacterial populations, fundamental knowledge is needed regarding how these mechanisms evolve to optimize for new host species or ecosystems.

This proposal aims to understand how different selective pressures shape the evolution of AR mechanisms. It will test the overall hypothesis that the dissemination of antibiotic-resistance mechanisms throughout a bacterial population requires the evolution of particular features that address the specific selective pressures of their environment. This information will also provide insight into how new dosing regimens with existing antibiotics might better resolve difficult-to-treat infections. The research team will analyze well-established and clinically relevant examples of resistance mechanisms that can be found in both environmental and clinical samples, characterizing their evolution during the adaptation to a new environment. They will seek to obtain a comprehensive understanding of the design principles of AR, through mechanistic studies that elucidate how AR emerges and is optimized in bacterial populations.