Decreased microbiota diversity associated with urinary tract infection in a trial of bacterial interference

Abstract

Background Patients with long-term indwelling catheters are at high risk of catheter-associated urinary tract infection (CAUTI). We hypothesized that colonizing the bladder with a benign E. coli strain (E. coli HU2117, a derivative of E. coli 83972 would prevent CAUTI in older, catheterized adults. Materials and Methods Adults with chronic, indwelling urinary catheters received study catheters that had been pre-coated with E. coli HU2117. We monitored the cultivatable organisms in the bladder for 28 days or until loss of E. coli HU2117. Urine from 4 subjects was collected longitudinally for 16S rRNA gene profiling. Results Eight of the ten subjects (average age 70.9 years) became colonized with E. coli HU2117, with a mean duration of 57.7 days (median: 28.5, range 0-266). All subjects also remained colonized by uropathogens. Five subjects suffered invasive UTI, 3 febrile UTI and 2 urosepsis/bacteremia, all associated with overgrowth of a urinary pathogen. Colonization with E. coli HU2117 did not impact bacterial bladder diversity, but subjects who developed infections had less diverse bladder microbiota. Conclusions Colonization with E. coli HU2117 did not prevent bladder colonization or subsequent invasive disease by uropathogens. Microbial diversity may play a protective role against invasive infection of the catheterized bladder.

Enterobacteria secrete an inhibitor of Pseudomonas virulence during clinical bacteriuria

“…This scenario may occur at epithelial surfaces during transient or persistent colonization of the urinary tract. The apparent ability of asymptomatic bacteriuria E. coli strain 83972 (or its derivative HU2117) to produce escherichelin during experimental human colonization is consistent with a model in which E. coli in the urinary tract secretes an antivirulence compound against P. aeruginosa (26,27). Expression of the virulence-associated Yersinia HPI in colonizing Enterobacteriaceae such as E. coli strain 83972 may thus confer both risk (from Ybt production) and benefit (escherichelin production) to patients (77).…”

“…This bioactivity and its production during human E. coli bacteriuria raises the possibility that escherichelin may help human hosts avoid developing symptomatic UTIs from pyochelin-producing organisms. Escherichelin was detectable in a human subject who was experimentally colonized with a derivative of the bacterial interference strain E. coli 83972 that has been studied in several human trials as a potential agent to prevent UTI (26,27). These findings reveal how a second metallophore product of the Yersinia HPI biosynthetic system may participate in interspecies competition during polymicrobial bacteriuria.…”

“…In subject 9, escherichelin was detected throughout the 57 days of documented HU2117 colonization, reaching a maximum on day 7 after catheterization ( Figure 5B). P. aeruginosa was detected by culture in the urine on day 7 but was unassociated with symptoms and became undetectable in subsequent specimens (27). On day 76, HU2117 colonization had ended, and the subject developed a febrile UTI caused by another E. coli strain, which was accompanied by detectable escherichelin.…”

“…In this context, an avirulent strain or species that outcompetes more pathogenic strains may be useful as a probiotic to prevent infections. E. coli 83972, which asymptomatically colonized a young Swedish girl for over 2 years (64), has been used in multiple UTI prevention studies (26,27,63,(65)(66)(67)(68)(69)(70). Among these studies are anecdotal reports of protection against symptomatic P. aeruginosa UTIs, including 1 patient with asymptomatic cocolonization of 83972 and P. aeruginosa that progressed to UTI following loss of 83972 (26,66).…”

“…To determine whether 83972 secretes escherichelin in the human urinary tract, we analyzed urine specimens following experimental colonization of catheter-dependent patients with an 83972-derived E. coli strain lacking the virulence-associated papG adhesin (E. coli HU2117) (27). Bladder colonization was established by inserting urinary catheters that had been precoated with E. coli HU2117.…”