Urinary Tract Infections (UTIs), one of the most prevalent bacterial infections globally, present a
formidable health challenge, especially considering that 25-50% of UTIs, even with antibiotic intervention,
either persist or recur within a six-month frame. The intricacy of managing recurrent UTI (rUTI) is amplified due
to the infiltration of the bladder epithelium by uropathogenic bacteria. Intracellular bacteria are safeguarded
from antibiotics that cannot penetrate epithelial cell membranes, thus facilitating their persistence to initiate
recurrent infections. Noteworthy studies by Co-Is De Nisco and Zimmern, utilizing 16S rRNA fluorescence in
situ hybridization to analyze bladder biopsies from women with rUTI, have confirmed the existence of tissue-
invasive bacteria within the bladder wall. The majority of available therapies are unable to target these tissue-
resident bacteria.
Electrofulguration (EF) is a therapy used to eradicate tissue-embedded bladder bacteria in women with
antibiotic-refractory UTI. By cauterizing visibly inflamed bladder areas, which are presumed to harbor tissue-
resident uropathogens, this treatment has provided symptomatic relief and reduced clinical incidence of rUTI.
However, its drawbacks include a six-month recovery period, pain, and the inability to differentiate between
infected and healthy tissue. Fulguration guidance relying on visual signs of inflammation hinders the specific
targeting of infected areas, potentially leading to the fulguration of healthy tissue and incomplete removal of
infected tissue. Therefore, targeted ablation of infected bladder areas is necessary to optimize outcomes for
rUTI patients and minimize pain and recovery duration.
A breakthrough from the Gassensmith lab has led to the development of BactVue, a novel tool
hypothesized to enable the targeted ablation of infected bladder tissue, potentially revolutionizing current
treatment paradigms for antibiotic-refractory UTI. BactVue, a bacteria-selective stain, can permeate the cellular
bilayer of epithelial cells, bind to intracellular bacteria, and, when irradiated with an 808 nm laser, fluoresce to
reveal the location of intracellular bacteria and cause photothermal heating that kills the bacteria and
selectively destroys the infected tissue. The proposal aims to define the potential of BactVue to specifically
target and ablate infected bladder tissue through photothermal heating, hypothesizing that BactVue binds
selectively to both Gram-negative and Gram-positive bacteria over mammalian cells.
The proposal outlines two primary aims: to demonstrate the ability of BactVue to stain diverse
intracellular uropathogenic bacteria selectively and to leverage photothermal heating to enable the targeted
killing of cells harboring pathogenic bacteria labeled with BactVue. The project promises to advance
significantly the development of this transformative tool for clinical applications in managing antibiotic-refractory
rUTI.
