In April of this year, lead authors John David Spencer, MD, Andrew Schwaderer, MD, and David Hains, MD, of the Division of Nephrology at Nationwide Children’s Hospital, and colleagues published a study in Kidney International that could change the future of medical therapy for urinary tract infections.
The study reports that the body’s urinary tract naturally produces a compound called Ribonuclease 7 (RNase 7), an antimicrobial peptide that fights bacteria. RNase 7 is now considered the most prevalent and potent known antimicrobial peptide in the human urinary tract. When an infection is present, the body boosts production of RNase 7 to kill the invading cells.
Michael Zasloff, MD, PhD, renowned for his work in innate immunity and antimicrobial peptides, describes the discovery as having “rewritten our current understanding of the antibacterial defenses of the human urinary tract.” Learning to manipulate the production of RNase 7 could open doors for the development of novel treatments for urinary tract infections.
Spencer, Schwaderer, and Hains’ research suggests that the broad-spectrum antimicrobial activity of RNase 7 may even be effective against uropathogenic bacteria that are resistant to conventional antibiotics. The peptide appears to work by binding to the bacterial cell and disrupting its microbial membrane, causing death of the bacterial cell. According to Dr. Spencer, this attack method makes it less likely that uropathogens will develop resistance to RNase 7.
“In addition, because RNase 7 is antibacterial at very minute concentrations,” says Dr. Spencer, “it may be much more potent than conventional antibiotics.”
Drs. Spencer and Schwaderer followed their April publication with a June report in Pediatric Nephrology reviewing the urinary tract’s innate immune response to microbial assault. Their team is trying to understand how different antimicrobial peptides work synergistically to prevent bacterial infections. They are currently evaluating regulatory proteins and enzymes in the urinary tract that control the antimicrobial activity of various peptides.
“We need to develop a better understanding of how antimicrobial peptides work at the bacterial cell wall so that we have a better understanding of how to develop them as novel therapeutics,” Dr. Spencer says. “We also need to learn how and why these peptides are produced by the kidney and bladder so that we can develop methods to regulate their expression or urinary levels.”
In time, the team hopes to use their work to help define the pathophysiology of common pediatric diseases, such as urinary tract infections, and create novel diagnostic and treatment strategies to improve patient care.
“If we can learn to manipulate these peptides or up-regulate them, we may be able to develop them as a new treatment,” Dr. Spencer says. “These findings could have a significant clinical impact.”
1 Spencer JD, Schwaderer AL, Wang H, Bartz J, Kline J, Eichler T, DeSouza KR, Sims-Lucas S, Baker P, Hains DS. Ribonuclease 7, an antimicrobial peptide upregulated during infection, contributes to microbial defense of the human urinary tract. Kidney International. 2013 Apr, 83(4): 615-625.
2 Zasloff M. The antibacterial shield of the human urinary tract. Kidney International. 2013 Apr, 83(4):548-550.
3 Spencer JD, Schwaderer AL, Becknell B, Watson J, Hains DS. The innate immune response during urinary tract infection and pyelonephritis. Pediatric Nephrology. 2013 Jun 5.