BactErase · Targeted Probes and Nanoparticles: Advancing Host-Driven Clearance of Recalcitrant Bacterial Pathogens

Antimicrobials are the cornerstone of modern medicine, essential for treating millions of people worldwide. Without effective antibiotics, even minor surgeries and routine operations could become high-risk procedures due to untreatable infections. Antimicrobials save lives and contribute, on average, 20 years to global life expectancy. However, the overuse of these drugs and the emergence of antibiotic-resistant bacteria are severely diminishing their therapeutic effects, making treatment increasingly difficult or even impossible. This phenomenon, known as antimicrobial resistance (AMR), is a growing health crisis that threatens to undermine the foundation of medical treatment that doctors, patients and public have come to rely on. Currently, an estimated 4.95 million deaths per year are associated with drug-resistant pathogens, with 1.27 million directly attributed to bacterial pathogens resistant to existing antibiotics. Hence, to address this urgent health challenge, new strategies are critically needed to contain, control and mitigated the spread of AMR. In this respect, BactErase proposes a novel host-directed therapy that leverage the natural ability of resident macrophage to utilize macroautophagy - a process that cells use to degrade and recycle intracellular components - to eradicate intracellular invaders. The primary goal of this proposal is to develop a bacteria-specific probe that can uniquely discriminate the bacteria within the cells and to design nanoparticles preferentially targeting infected cells. This approach aims to enhance the host’s intrinsic ability to resolve drug-recalcitrant infections while minimizing the risk of antimicrobial resistance development. By exploiting the host’s own mechanisms for bacterial clearance in conjunction with selective nanoparticle delivery, BactErase offers an attractive alternative to conventional antibiotic therapy, potentially remodulating the treatment of infectious disease.