Immune Modulation by Group B Streptococcus Influences Host Susceptibility to Urinary Tract Infection by Uropathogenic Escherichia coli

Abstract

Urinary tract infection (UTI) is most often caused by uropathogenic Escherichia coli (UPEC). UPEC inoculation into the female urinary tract (UT) can occur through physical activities that expose the UT to an inherently polymicrobial periurethral, vaginal, or gastrointestinal flora. We report that a common urogenital inhabitant and opportunistic pathogen, group B Streptococcus (GBS), when present at the time of UPEC exposure, undergoes rapid UPEC-dependent exclusion from the murine urinary tract, yet it influences acute UPEC-host interactions and alters host susceptibility to persistent outcomes of bladder and kidney infection. GBS presence results in increased UPEC titers in the bladder lumen during acute infection and reduced inflammatory responses of murine macrophages to live UPEC or purified lipopolysaccharide (LPS), phenotypes that require GBS mimicry of host sialic acid residues. Taken together, these studies suggest that despite low titers, the presence of GBS at the time of polymicrobial UT exposure may be an overlooked risk factor for chronic pyelonephritis and recurrent UTI in susceptible groups, even if it is outcompeted and thus absent by the time of diagnosis.

Impact of Host Age and Parity on Susceptibility to Severe Urinary Tract Infection in a Murine Model

“…UPEC titers were similar in the presence or absence of GBS ( Fig. 1A&C ) whereas, consistent with our previous findings in young mice where we observed that GBS were rapidly cleared after co-infection with UPEC [3], GBS were rapidly cleared when UPEC were also present in the inoculum ( Fig. 1B&D ).…”

Discovery and Characterization of Human-Urine Utilization by Asymptomatic-Bacteriuria-Causing Streptococcus agalactiae

“…Recent data from Kline et al showed that the presence of S. agalactiae in the urinary tract in mice could predispose the host to other uropathogenic bacteria such as E. coli (83). Our findings suggest that ABSA strains that colonize urine more efficiently may have the potential to modify the progression of UTIs due to other causal organisms in some individuals.…”

Spectrum of Bacterial Colonization Associated with Urothelial Cells from Patients with Chronic Lower Urinary Tract Symptoms

“…Although the conventional wisdom holds that urine is sterile, the urethra connects the bladder to the outside environment, so it is not surprising that biological adaptation would enable commensal organisms to reside there. Indeed, reports of bacteriuria in normal controls are found in the literature (8,34,35). A reason why these commensal organisms are not readily detected may lie in the insensitivity of routine cultures, as shown here and by others previously (5)(6)(7)9).…”

“…Some of Kass' contemporaries criticized the use of a single threshold for diagnosing UTI in all diseases (5,6), and recently we and others also have come to question these assumptions (7)(8)(9). Biological systems fall along continuous spectra; therefore, a dichotomous judgment of no infection/significant infection using a fixed point, whether this be 10 5 , 10 4 , or 10 2 CFU ml Ϫ1 (9), may be inappropriate, especially for low-grade symptomatic infections.…”