This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Urinary Tract Infections (UTIs) constitute a significant economical burden for the US health system. Our initial goal was identification and characterization of antimicrobial peptides (AMPs) - including beta-defensin - in urogenital tissues using a canine model. UTIs in humans and dogs are much alike, making a canine model suitable to study this disorder. In addition, dogs are known to be more resistant to sexually transmitted diseases (STDs) in comparison to humans. We therefore theorized that the urogenital AMPs expression pattern would likely explain the cause of this pronounced resilience. To date, we have characterized the molecular structure, and assessed the antimicrobial activity and salt sensitivity of three novel canine testicular beta-defensins and one cathelicidin primarily expressed in white blood cells (e.g. neutrophils). We focused on the biological characterization of canine cathelicidin (K9CATH) in white blood cells. RT-PCR, Southern Blot, and Real-Time PCR methods were used. Synthetic K9CATH displayed broad and salt-independent antimicrobial activity against Gram-positive and Gram-negative bacteria as well as yeast. The peptide also displayed minimal hemolytic activity against human, dog and chicken red blood cells. The broad killing capacity and unique biochemical resistance of K9CATH would suggest that this immune effector molecule is capable of functioning under very different micro-environmental conditions, which may enable it with even wider immunological applications. The dog may be used as a key animal model for investigation of urogenital AMP regulatory mechanisms, thereby providing novel information leading to further understanding of human UTIs.
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