Antibiotics of the future: are they prone to bacterial resistance?

Introduction

Although several new antibiotic candidates are in the clinical pipeline, the future evolution of resistance in bacteria may render them ineffective. This project aims to develop a framework for forecasting the long-term effectiveness of new antibiotic candidates.

Objectives

For this purpose, we will decipher the general principles shaping bacterial resistance to a wide range of antibiotic candidates currently in development. Using recently developed methods in our laboratory, we will study resistance evolution in bacterial ESKAPE pathogens at unprecedented resolution and address four specific aims:

1. Shared Features of Antibiotics
   We explore the shared features of antibiotics with limited susceptibility to resistance.

2. Species-Specific Differences
   We systematically map species-specific differences in resistance evolution with implications on narrow-spectrum antibacterial therapies that could remain effective.

3. Clinical Risks Assessment
   We assess the clinical risks associated with resistance by studying the global biogeography and habitat-specificity of resistant bacteria.

4. Links Between Resistance and Virulence
   Finally, we systematically explore the potential links between resistance evolution and increased bacterial virulence.

Expected Outcomes

The outcomes will provide guidelines for future antibiotic use, aid in genomic surveillance of resistance genes, and facilitate the design of antibiotics with reduced susceptibility to resistance.