The latest in the body of antimicrobial peptide research suggests RNase7 may be a prognostic marker and potential therapeutic option for UTIs.
Building on their body of research focused on the naturally occurring antimicrobial peptides in the urinary tract, clinician-scientists at Nationwide Children’s Hospital have now confirmed the suspected role of Ribonuclease 7 (RNase 7) in E. coli-based infection risk. Human patients, tissue cultures and humanized mouse models all indicate that higher levels of RNase 7 in the urinary tract are associated with lower risk of infection, and lower levels of RNase 7 are associated with increased susceptibility to infection.
According to the research team, this suggests a potential role for RNase 7 in the prediction of infection risk or severity as well as in the development of novel, non-antibiotic treatments — even for drug-resistant UTIs.
“For the first time, we’ve shown that female children with UTIs have lower levels of the antimicrobial peptide RNase 7 compared to healthy controls,” says John David Spencer, MD, chief of the Division of Nephrology and Hypertension at Nationwide Children’s and senior author on the study, published in the Journal of the American Society of Nephrology.
The study’s 29 girls who had a UTI history had an average urinary RNase 7 concentration 1.5 times lower than the 29 healthy control girls.
Additionally, the publication included findings from human tissue cultures showing that silencing RNase 7 allowed a multi-drug resistant strain of E. coli (known as uropathogenic E. coli or UPEC) to bind more effectively to human bladder cells, while overexpressing RNase 7 led to decreased bacterial binding.
The team also developed a humanized mouse model to express high and low levels of RNase 7 in the urinary tract in order to study its biological activity. This first-ever manipulation of RNase 7 in vivo revealed that mice with RNase 7 present had low susceptibility to infection when challenged with UPEC.
“This study represents a key step in trying to evaluate the biological activity and safety profile of RNase 7 manipulation,” says Dr. Spencer, whose work on antimicrobial peptides is supported by funding through the National Institutes of Health. “Our research suggests that if you can find a way to overexpress the RNase 7 protein, it could be a therapy. It also further validates that if you have lower levels of RNase 7, you may be at greater risk for infection.”
Eichler T, Bender K, Murtha MJ, Schwartz L, Metheny J, Solden L, Jaggers RM, Bailey MT, Gupta S, Mosquera C, Ching C, La Perle K, Li B, Becknell B, Spencer JD. Ribonuclease 7 Shields the Kidney and Bladder from Invasive Uropathogenic Escherichia coli Infection. J Am Soc Nephrol. 2019 Aug;30(8):1385-1397.
Murtha MJ, Eichler T, Bender K, Metheny J, Li B, Schwaderer AL, Mosquera C, James C, Schwartz L, Becknell B, Spencer JD. Insulin receptor signaling regulates renal collecting duct and intercalated cell antibacterial defenses. The Journal of Clinical Investigation. 2018 Dec 3;128(12):5634-5646.
In the past decade, the Division of Nephrology and Hypertension has received national recognition and awards for clinical research. The Nephrology and Urology Research Affinity Group (NURAG) at Nationwide Children’s has received over $18.7 million in extramural funding between 2015-2020.
- 2012: Nephrologists Invest in Patient Advocacy by Becoming John E. Lewy (JELF) Scholars through American Society of Pediatric Nephrology
- 2013: New Multidisciplinary Nephro-Urology and Kidney Stone Clinic Starts in Collaboration with Urology
- 2017: New Multidisciplinary Lupus Clinic Starts in Collaboration with Rheumatology
- 2019: First Simultaneous Liver-Kidney Transplant at Nationwide Children’s
- 2020: Division Rebranded to Division of Nephrology and Hypertension