Role of Urinary Cathelicidin LL-37 and Human β-Defensin 1 in Uncomplicated Escherichia coli Urinary Tract Infections

Abstract

; Haslev Laegecenter, Haslev, Denmark c ; Laegehuset Ellemarksvej, Køge, Denmark d Cathelicidin (LL-37) and human ␤-defensin 1 (hBD-1) are important components of the innate defense in the urinary tract. The aim of this study was to characterize whether these peptides are important for developing uncomplicated Escherichia coli urinary tract infections (UTIs). This was investigated by comparing urinary peptide levels of UTI patients during and after infection to those of controls, as well as characterizing the fecal flora of participants with respect to susceptibility to LL-37 and in vivo virulence. Forty-seven UTI patients and 50 controls who had never had a UTI were included. Participants were otherwise healthy, premenopausal, adult women. LL-37 MIC levels were compared for fecal E. coli clones from patients and controls and were also compared based on phylotypes (A, B1, B2, and D). In vivo virulence was investigated in the murine UTI model by use of selected fecal isolates from patients and controls. On average, UTI patients had significantly more LL-37 in urine during infection than postinfection, and patient LL-37 levels postinfection were significantly lower than those of controls. hBD-1 showed similar urine levels for UTI patients and controls. Fecal E. coli isolates from controls had higher LL-37 susceptibility than fecal and UTI E. coli isolates from UTI patients. In vivo studies showed a high level of virulence of fecal E. coli isolates from both patients and controls and showed no difference in virulence correlated with the LL-37 MIC level. The results indicate that the concentration of LL-37 in the urinary tract and low susceptibility to LL-37 may increase the likelihood of UTI in a complex interplay between host and pathogen attributes.

Low intestinal colonization of Escherichia coli clone ST131 producing CTX-M-15 in Jordanian infants

“…The human intestine is a major reservoir for extra-intestinal pathogenic E. coli strains; especially, urinary tract infections are mostly caused by patients' own faecal E. coli (Ejrnaes, 2011;Nielsen et al, 2014). Faecal E. coli is also a frequent cause of extra-intestinal infections in infants in the form of meningitis and blood sepsis (Korhonen et al, 1985).…”

Amplifying renal immunity: the role of antimicrobial peptides in pyelonephritis

“…53,80 Mature HBD-1 is constitutively detected in sterile urine at concentrations of 10-100 μg/l or 3.5-316 mg/g of creatinine, with higher urinary levels in pregnant women. 53,62 Urinary HBD-1 levels increase up to threefold in patients with acute pyelonephritis, whereas by contrast, studies suggest HBD-1 levels are not induced in cystitis. 62,81 In women undergoing pelvic floor surgery for urinary incontinence or pelvic organ prolapse, urinary HBD-1 levels were lower in patients with preoperative positive urine cultures.…”

“…Low levels of LL-37 are detected in sterile urine and urinary LL-37 concentrations increase in the presence of cystitis and pyelonephritis. 61,62 In human kidney biopsy specimens, LL-37 production increased following exposure to UPEC. 61 Similarly, administration of UPEC to renal epithelial cells (A498 and hPTC cells) and urothelial cells (J82 and UROtsa cells) in vitro resulted in rapid increases in CAMP mRNA expression followed by prolonged LL-37 peptide secretion.…”

A retrospective study of antibiotic sensitivity pattern of uropathogens in the Federal Capital Territory, Nigeria

“…For instance, the protein beta defensin-1 (BD1) and Cathelicidin (LL-37) peptide shows constitutive expression in the urinary tract, as both molecules from previous studies have demonstrated to play key roles in UTI's mitigation (Mambula et al, 2000;Chromek et al, 2006). Also, in a study of uncomplicated UTI subject, elevated level of LL-37 was observed (Nielsen et al, 2014), whilst E. coli isolates from healthy controls exhibited more susceptibility to LL-37 than isolates from UTI patients. Further, BD1 has also exhibited constitutive expression in the urinary tract and hence, BD1 is suggested to play a role in pyelonephritis (Smith et al, 2011;Mambula et al, 2000;Morrison et al, 2002) and act as a defence against Gram-positive uropathogens (Morrison et al, 2002).…”