[R01] Roles of RNase3, RNase6, and Ribonuclease Inhibitor in Bacterial Urinary Tract Infection
Ente: National Institute of Diabetes and Digestive and Kidney Diseases
Scadenza: 2031-05-31
Importo max: 795.317 EUR
Paese: US
Descrizione
PROJECT SUMMARY / ABSTRACT
Urinary tract infections (UTI) are common, serious bacterial infections that originate in the bladder and can
ascend to the kidney, leading to acute kidney injury and long-term sequelae such as renal scarring and chronic
kidney disease. There are no proven strategies to prevent UTI sequelae, and uropathogenic bacteria are
increasingly resistant to antibiotics. Antimicrobial peptides (AMPs) shield the urinary tract from invading bacteria
and have therapeutic potential for UTI prevention and treatment. Our research team has implicated Ribonuclease
(RNase)3 and RNase6 as potent, phagocyte-derived AMPs in the human urinary tract, but their specific roles
and regulation during UTI remain unknown. This knowledge gap limits the development of RNase3 and RNase6
as novel therapeutic agents to combat UTI.
To determine the impact of RNase3 and RNase6 during experimental UTI, we have engineered RNASE3 and
RNASE6 transgenic mice. In Specific Aim 1, we propose experiments to determine the impact of these
transgenes, both alone and in combination, on host UTI susceptibility by focusing on their antimicrobial and
immunomodulatory effects. In Specific Aim 2, we will determine the role of Ribonuclease Inhibitor (RI) in
governing the antimicrobial activity of RNase3 and Rnase6 during UTI. In Specific Aim 3, we will investigate how
RI and Pi3K/Akt signaling impact phagocyte UTI defenses. Completion of these studies will advance our
knowledge of AMP function and regulation during UTI and give further impetus to the development of AMP-
based therapeutic strategies for prevention and treatment of UTI and mitigation of UTI sequelae.
Istituzione: RESEARCH INST NATIONWIDE CHILDREN'S HOSP
PI: Brian Becknell
Progetto: 1R01DK141592-01A1
Settori: National Institute of Diabetes and Digestive and Kidney Diseases
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