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Abstract: PO2275

Human Neutrophil Peptide 1-3 Protects the Urinary Tract from Uropathogenic Escherichia coli Invasion in Humanized Mouse Model

Session Information

Category: Pediatric Nephrology

  • 1700 Pediatric Nephrology

Authors

  • Canas, Jorge Jose, Division of Pediatric Nephrology, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Hooks, Jenaya, Division of Pediatric Nephrology, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Arregui, Sam W., Division of Pediatric Nephrology, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Schwaderer, Andrew L., Division of Pediatric Nephrology, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Hains, David S., Division of Pediatric Nephrology, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, United States
Background

Urinary tract infection (UTI) susceptibility is defined by heritable genetic differences associated with the innate immune system development and efficiency. DNA copy number variations in the alpha-defensin DEFA1A3 locus are associated with UTI susceptibility in children with VUR. In humans, DEFA1A3 is expressed in neutrophils as well as in the kidney. However, how DEFA1A3 protects the urinary tract in some individuals is unknown. We hypothesized that Defa+/+ humanized mouse would be resistant to experimental UTI.

Methods

We induced UTI with two uropathogenic E. coli (UPEC) strains in wild-type (WT) C57Bl/6J and Defa+/+ transgenic mice, which express human DEFA1A3. Bacterial suspension was inoculated with a catheter transurethrally. To asses the colony-forming-unit (CFU) burden, kidneys and bladders were homogenized and colony forming units and clearance were determined by quantifying the plating serial dilutions grown overnight on LB plates at various time points.

Results

Results are presented in Figure 1: Comparing the Defa+/+ mouse to WT (n=8 for each group), at 6-hours post infection, bacterial burdens were lower in the Defa+/+ mice kidneys for both UPEC strains (A). At 24-hours after inoculum, the mean bladder Log (CFU/g) was significantly lower in the Defa+/+ mouse in comparison to the C57Bl/6J group (B).

Conclusion

Our findings support the early protective role of DEFA1A3 from UPEC challenge in the humanized mouse kidney and bladder when compared to the absence of the antimicrobial peptide in the wild-type mouse. Further investigation is needed to determine whether renal or extra-renal expression of DEFA1A3 is critical in shielding and clearing UPEC UTIs.

Kidney and Bladder CFU Burden upon UPEC inoculation

Funding

  • NIDDK Support