title: Interplay between bladder microbiota and urinary antimicrobial peptides: mechanisms for human urinary tract infection risk and symptom severity.
abstract: 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.
authors.affiliation: The Burn and Shock Trauma Research Institute at Loyola University Chicago, Health Sciences Division, Maywood, Illinois, United States of America; Department of Microbiology and Immunology at Loyola University Chicago, Health Sciences Division, Maywood, Illinois, United States of America; Stritch School of Medicine at Loyola University Chicago, Health Sciences Division, Maywood, Illinois, United States of America; Infectious Disease and Immunology Research Institute at Loyola University Chicago, Health Sciences Division, Maywood, Illinois, United States of America.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Nienhouse
authors.affiliation: Department of Biological Sciences, University of North Texas, Denton, Texas, United States of America; Department of Computer Science and Engineering, University of North Texas, Denton, Texas, United States of America.
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Biological Sciences, University of North Texas, Denton, Texas, United States of America; Department of Computer Science and Engineering, University of North Texas, Denton, Texas, United States of America.
authors.forename: Qunfeng
authors.initials: Q
authors.lastname: Dong
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: David E
authors.initials: DE
authors.lastname: Nelson
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Toh
authors.affiliation: Department of Pathology at Loyola University Chicago, Health Sciences Division, Maywood, Illinois, United States of America.
authors.forename: Kathleen
authors.initials: K
authors.lastname: McKinley
authors.affiliation: Stritch School of Medicine at Loyola University Chicago, Health Sciences Division, Maywood, Illinois, United States of America; Infectious Disease and Immunology Research Institute at Loyola University Chicago, Health Sciences Division, Maywood, Illinois, United States of America; Department of Pathology at Loyola University Chicago, Health Sciences Division, Maywood, Illinois, United States of America.
authors.forename: Paul
authors.initials: P
authors.lastname: Schreckenberger
authors.affiliation: Department of Microbiology and Immunology at Loyola University Chicago, Health Sciences Division, Maywood, Illinois, United States of America; Infectious Disease and Immunology Research Institute at Loyola University Chicago, Health Sciences Division, Maywood, Illinois, United States of America.
authors.forename: Noriko
authors.initials: N
authors.lastname: Shibata
authors.affiliation: Stritch School of Medicine at Loyola University Chicago, Health Sciences Division, Maywood, Illinois, United States of America; Department of Obstetrics/Gynecology, Division of Female Pelvic Medicine and Reconstructive Surgery at Loyola University Chicago, Health Sciences Division, Maywood, Illinois, United States of America; Department of Urology at Loyola University Chicago, Health Sciences Division, Maywood, Illinois, United States of America.
authors.forename: Cynthia S
authors.initials: CS
authors.lastname: Fok
authors.affiliation: Stritch School of Medicine at Loyola University Chicago, Health Sciences Division, Maywood, Illinois, United States of America; Department of Obstetrics/Gynecology, Division of Female Pelvic Medicine and Reconstructive Surgery at Loyola University Chicago, Health Sciences Division, Maywood, Illinois, United States of America; Department of Urology at Loyola University Chicago, Health Sciences Division, Maywood, Illinois, United States of America.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Mueller
authors.affiliation: Stritch School of Medicine at Loyola University Chicago, Health Sciences Division, Maywood, Illinois, United States of America; Department of Obstetrics/Gynecology, Division of Female Pelvic Medicine and Reconstructive Surgery at Loyola University Chicago, Health Sciences Division, Maywood, Illinois, United States of America; Department of Urology at Loyola University Chicago, Health Sciences Division, Maywood, Illinois, United States of America.
authors.forename: Linda
authors.initials: L
authors.lastname: Brubaker
authors.affiliation: Department of Microbiology and Immunology at Loyola University Chicago, Health Sciences Division, Maywood, Illinois, United States of America; Stritch School of Medicine at Loyola University Chicago, Health Sciences Division, Maywood, Illinois, United States of America; Infectious Disease and Immunology Research Institute at Loyola University Chicago, Health Sciences Division, Maywood, Illinois, United States of America.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Wolfe
authors.affiliation: The Burn and Shock Trauma Research Institute at Loyola University Chicago, Health Sciences Division, Maywood, Illinois, United States of America; Department of Microbiology and Immunology at Loyola University Chicago, Health Sciences Division, Maywood, Illinois, United States of America; Stritch School of Medicine at Loyola University Chicago, Health Sciences Division, Maywood, Illinois, United States of America; Infectious Disease and Immunology Research Institute at Loyola University Chicago, Health Sciences Division, Maywood, Illinois, United States of America; Department of Surgery at Loyola University Chicago, Health Sciences Division, Maywood, Illinois, United States of America.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Radek
mesh_terms: D000249:Adenosine Monophosphate / Q000737:chemistry / Q000652:urine; D000890:Anti-Infective Agents / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000652:urine*; D001419:Bacteria / Q000145:classification / Q000187:drug effects / Q000235:genetics; D044822:Biodiversity; D015331:Cohort Studies; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008826:Microbial Sensitivity Tests; D064307:Microbiota; D010447:Peptide Hydrolases / Q000652:urine; D010802:Phylogeny; D012307:Risk Factors; D012720:Severity of Illness Index; D001743:Urinary Bladder / Q000382:microbiology*; D014552:Urinary Tract Infections / Q000175:diagnosis / Q000382:microbiology* / Q000652:urine*; D023083:beta-Defensins / Q000652:urine
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; C406407:DEFB1 protein, human; D023083:beta-Defensins; D000249:Adenosine Monophosphate; D010447:Peptide Hydrolases