(From the February 2015 Issue of Research Now)
Recent research conducted by a team of clinician scientists in The Research Institute at Nationwide Children’s Hospital has identified Ribonuclease 6 (RNase 6) as an antimicrobial peptide that helps maintain the sterility of the urinary tract and is critical in preventing urinary tract infections (UTIs). Findings from this latest study were published in the January issue of Kidney International by John David Spencer, MD and Brian Becknell, MD, PhD, nephrologists and principal investigators in the Center for Clinical and Translational Research, and colleagues at Nationwide Children’s and collaborating institutions.
Although the human kidneys and urinary tract are constantly exposed to harmful bacteria, only 3 percent of all children develop UTIs each year. However, many children suffer from recurrent and serious UTIs, resulting in more than 1 million pediatric visits due to UTIs annually. Drs. Spencer and Becknell hypothesize that the production or absence of antimicrobial peptides may be a primary reason that some individuals are more susceptible to UTIs.
Antimicrobial peptides are naturally produced in the skin, colon and a number of other organs. They have have potent antibiotic activity, shielding the body from infection-causing pathogens and often prevent illness altogether.
“Earlier studies conducted by our team revealed a new family of ribonucleases present in human and mouse – or murine – urinary tracts,” says Dr. Spencer. “These proteins, which are part of the RNase A Superfamily, have significant antimicrobial properties when they function properly, shielding the body against UTIs.” In their latest study, Drs. Becknell and Spencer identify RNase 6 as the newest member of the RNase A Superfamily that has potent antimicrobial properties in humans and mice.
Using methods such as real-time PCR and immunoblot analysis, researchers were able to detect RNase 6 and characterize its expression in the human and murine urinary tract during infection. In order to determine the specific location of RNase 6, the team used immunostaining and determined that RNase 6 was found in resident and infiltrating monocytes, macrophages and neutrophils.
“Our findings demonstrate that RNase 6 mRNA and protein are upregulated in the human and murine urinary tract during infection,” explains Dr. Becknell, who is also an assistant professor in Pediatrics at The Ohio State University College of Medicine, along with Dr. Spencer. “In particular, we found that uropathogenic E. coli, which account for more than 80% of uncomplicated UTIs, induces expression of RNase 6 peptide in human CD14(+) monocytes and murine bone marrow-derived macrophages.”
According to Drs. Spencer and Becknell, understanding how antimicrobial peptides like RNase 6 function in vivo in the human urinary tract is crucial in developing therapeutics that could help decrease the occurrence of UTIs for susceptible individuals. However, further studies need to be conducted to determine whether higher levels of antimicrobial peptides are necessarily beneficial, or if they might have harmful effects when over-activated.
“Our team is currently working to better elucidate the role that antimicrobial peptides may have in the treatment of a wide range of infections, including UTIs,” says Dr. Spencer. “Future studies will focus on the mechanisms by which antimicrobial peptide production is upregulated and whether antimicrobial peptides are more effective at preventing urinary tract infections than traditional antibiotics.”
Becknell B, Eichler TE, Beceiro S, Li B, et al. Ribonucleases 6 and 7 have antimicrobial function in the human and murine urinary tract. Kidney International. 2014 Jul 30. [Epub ahead of print.]
Brind’Amour, Katie. Body, Health Thyself: Harnessing Our Innate Immunity. Pediatrics Nationwide. Fall/Winter 2014. Epub online: November 10, 2014.