Resident bacterial communities (microbiota) and host antimicrobial peptides (AMPs) are both essential components of normal host innate immune responses that limit infection and pathogen induced inflammation. However, their interdependence has not been investigated in the context of urinary tract infection (UTI) susceptibility. Here, we explored the interrelationship between the urinary microbiota and host AMP responses as mechanisms for UTI risk. Using prospectively collected day of surgery (DOS) urine specimens from female pelvic floor surgery participants, we report that the relative abundance and/or frequency of specific urinary microbiota distinguished between participants who did or did not develop a post-operative UTI. Furthermore, UTI risk significantly correlated with both specific urinary microbiota and β-defensin AMP levels. Finally, urinary AMP hydrophobicity and protease activity were greater in participants who developed UTI, and correlated positively with both UTI risk and pelvic floor symptoms. These data demonstrate an interdependency between the urinary microbiota, AMP responses and symptoms, and identify a potential mechanism for UTI risk. Assessment of bacterial microbiota and host innate immune AMP responses in parallel may identify increased risk of UTI in certain populations.

Objectives Characterization of urinary bacterial microbiome and antimicrobial peptides (AMPs) after burn injury to identify potential mechanisms leading to urinary tract infections (UTIs) and associated morbidities in burn patients. Design Retrospective cohort study using human urine from control and burn subjects. Setting University Research Laboratory. Patients Burn patients. Interventions None. Measurements and Main Results Urine samples from catheterized burn patients were collected hourly for up to 40 hours. Control urine was collected from “healthy” volunteers. The urinary bacterial microbiome and AMP levels and activity were compared with patient outcomes. We observed a significant increase in urinary microbial diversity in burn patients vs. controls, which positively correlated with a larger percent burn and with the development of UTI and sepsis post-admission, regardless of age or gender. Urinary psoriasin and β-defensin AMP levels were significantly reduced in burn patients at 1 and 40 hours post-admission. We observed a shift in AMP hydrophobicity and activity between control and burn patients when urinary fractions were tested against Escherichia coli and Enterococcus faecalis UTI isolates. Furthermore, the AMP activity in burn patients was more effective against E. coli than E. faecalis. UTI-positive burn patients with altered urinary AMP activity developed either an E. faecalis or Pseudomonas aeruginosa UTI, suggesting a role for urinary AMPs in susceptibility to select uropathogens. Conclusions Our data reveal potential links for UTI development and several morbidities in burn patients through alterations in the urinary microbiome and AMPs. Overall, this study supports the concept that early assessment of urinary AMP responses and the bacterial microbiome may be used to predict susceptibility to UTIs and sepsis in burn patients.

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