Grant: Travel Awards - Institute Community Support

Urinary tract infections (UTIs) are one of the most common bacterial infections, and most are caused by a type of bacteria called uropathogenic Escherichia coli (UPEC). While antibiotics are usually effective for initial infections, more than one in four people experience recurrent UTIs (rUTIs). A major reason for recurrence is that UPEC can survive quietly in the gut during remission and later move back into the urinary tract, causing new infections. Current treatment for rUTIs relies on long-term or repeated antibiotic use. Unfortunately, this approach can lead to antibiotic-resistant bacteria and also disrupt helpful gut microbes that normally protect against infection. This creates a vicious cycle where treatment may actually increase vulnerability to future UTIs. Our research aims to break this cycle by tackling a root cause of rUTIs - persistent reservoirs of UPEC bacteria in the gut-without relying on antibiotics. We are developing synthetic "living" therapeutics, called synthetic anti-UPEC microbial therapeutics (synAMTs), that are designed to actively find and eliminate UPEC in the gut microbiome while leaving beneficial bacteria unharmed. These engineered bacteria use highly specific targeting molecules on their surface to recognize UPEC and then deliver a natural bacterial "weapon" to kill them only on contact. This project brings together expertise in infectious diseases and synthetic biology. We have two main goals: (1) to create and test prototype synAMTs that selectively remove UPEC from the gut, and (2) to develop realistic lab models using samples from patients with UTIs to evaluate and refine these synAMTs under conditions that mimic the human gut. Our work represents a new, antibiotic-free strategy for preventing recurrent UTIs at their source.