Tolerance of bacteriuria after urinary diversion is linked to antimicrobial peptide activity

Abstract

Objectives: To compare the cationic antimicrobial peptide gene expression profiles and urinary cationic antimicrobial activities of patients after urinary diversion according to their urinary tract infection (UTI) status. Ileal conduit urinary diversion joins the bacterial-tolerant ileal epithelium and intolerant urothelium. After this procedure, one quarter of patients develop repeated symptomatic UTIs. Such development might reflect the altered innate immune mechanisms centered on epithelial expression and urinary activity of cationic antimicrobial peptides, such as defensins.

Methods: Ileal and ureteral biopsy specimens from ileal conduit subjects with (n = 18) and without (n = 18) recurrent symptomatic UTIs were assessed for cationic antimicrobial peptide gene expression using quantitative reverse transcriptase polymerase chain reaction. Overnight urine collections were analyzed for antimicrobial activity against a laboratory Escherichia coli strain, and infecting organisms were isolated from individual subjects.

Results: Overall, the ureteral epithelium showed increased expression of human α-defensin 5 and decreased expression of the human β-defensin 1 after urinary diversion (P < .05). No significant changes were seen for the ileal epithelium. The expression levels of both defensins also did not differ significantly according to UTI status. Urinary cationic activity against infecting bacterial isolates from the individual subjects was significantly greater in those with symptomatic UTI (P < .001), and the activities against the laboratory E. coli strain were similar.

Conclusions: The changes in the human β-defensin 1 and human α-defensin 5 expression profiles and the link between symptomatic infection and high urinary antimicrobial activity suggest that innate mechanisms play significant roles in balancing bacterial tolerance and killing after ileal conduit urinary diversion. Future work needs to determine whether these changes can be therapeutically modulated to benefit the patients.