Grant: Project Grant

Antibiotic resistance is a growing global health crisis, making infections harder to treat and reducing the effectiveness of life-saving medicines. New antibiotics are difficult to develop, so we are exploring alternative strategies to combat resistant bacteria. One promising approach is collateral sensitivity - a phenomenon where bacteria that become resistant to one antibiotic unexpectedly become more vulnerable to another. If we can systematically uncover these hidden weaknesses, we may be able to design better treatment strategies that slow resistance and restore the effectiveness of existing antibiotics. Our research has already demonstrated how this approach can work. We discovered that disrupting bacterial fatty acid metabolism can make drug-resistant bacteria susceptible to colistin, an antibiotic of last resort. In another study, we found that bacteria resistant to carbapenems - powerful antibiotics used for severe infections - become more sensitive to inhibitors of cell envelope stress. These findings suggest that when bacteria evolve resistance, they also develop vulnerabilities that can be exploited for treatment. To expand this research, we have developed a powerful genetic tool based on CRISPR technology that allows us to systematically study resistance mechanisms at a large scale. We propose to use this tool to map genetic and metabolic weak spots in resistant bacteria, identifying new treatment strategies that could extend the lifespan of existing antibiotics. By uncovering and targeting the hidden costs of resistance, this work has the potential to improve treatment options for drug-resistant infections and slow the spread of resistance, ultimately protecting public health.