Uropathogenic Escherichia coli Induces Chronic Pelvic Pain

Abstract

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a debilitating syndrome of unknown etiology often postulated, but not proven, to be associated with microbial infection of the prostate gland. We hypothesized that infection of the prostate by clinically relevant uropathogenic Escherichia coli (UPEC) can initiate and establish chronic pain. We utilized an E. coli strain newly isolated from a patient with CP/CPPS (strain CP1) and examined its molecular pathogenesis in cell culture and in a murine model of bacterial prostatitis. We found that CP1 is an atypical isolate distinct from most UPEC in its phylotype and virulence factor profile. CP1 adhered to, invaded, and proliferated within prostate epithelia and colonized the prostate and bladder of NOD and C57BL/6J mice. Using behavioral measures of pelvic pain, we showed that CP1 induced and sustained chronic pelvic pain in NOD mice, an attribute not exhibited by a clinical cystitis strain. Furthermore, pain was observed to persist even after bacterial clearance from genitourinary tissues. CP1 induced pelvic pain behavior exclusively in NOD mice and not in C57BL/6J mice, despite comparable levels of colonization and inflammation. Microbial infections can thus serve as initiating agents for chronic pelvic pain through mechanisms that are dependent on both the virulence of the bacterial strain and the genetic background of the host.Prostatitis is a common urologic disease that results in over 2 million outpatient visits per year in the United States, including 8% of all visits to urologists and 1% of those to primary care physicians (5). The disease is classified into four categories, including acute bacterial prostatitis, chronic bacterial prostatitis, chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), and asymptomatic inflammatory prostatitis.The third disease category, CP/CPPS, accounts for approximately 90% of all chronic prostatitis cases and is clinically manifested as chronic pain in the perineum, rectum, prostate, penis, testicles, and abdomen (5). Despite the predominantly nonbacterial nature of CP/CPPS, up to 8% of patients with CP/CPPS harbor uropathogens that have traditionally been deemed to be of no significance (25). Numerous studies have also identified bacterial DNA in prostate samples from CP/ CPPS patients (9,19,20,22,25). CP/CPPS accompanied by uropathogens is differentiated from chronic bacterial prostatitis by the requirement for clinical symptoms of pelvic pain and the lack of recurrent urinary tract infections (UTIs).It has been suggested that the virulence of major uropathogens such as UPEC is dependent on the expression of multiple virulence factors (10, 15). Phylogenetic analysis suggests that prostatitis-causing uropathogenic Escherichia coli (UPEC) strains largely belong to the B2 phylogenetic group and exhibit a wide variety of virulence traits, including nonhemagglutinin adhesin-siderophore receptor (ihA), type 1 fimbriae (fimH), the salmochelin siderophore receptor (iroN), and outer membrane protease T (ompT) (1,12,...

Measurement of Tactile Allodynia in a Murine Model of Bacterial Prostatitis

“…The present study uses a well-characterized prostate-derived chronic prostatitis UPEC strain to mediate disease 2 . Earlier studies have used bacteria derived from bladder infections or acute prostatitis that was utilized primarily for examining inflammation associated events but not characterized in terms of tactile allodynia…”

Mechanisms of the harmful effects of bacterial semen infection on ejaculated human spermatozoa: potential inflammatory markers in semen

“…Another type of adhesins, namely P fimbriae, are important and widely studied mannose-resistant adhesion molecules present in 40-60% of uropathogenic (UPEC) isolates [37]. High incidences of P-fimbriated E. coli strains have been found in acute prostatitis [38]. Our experience with P-fimbriated E. coli serotype O75:HNT has confirmed direct contact adhesion to the surface of sperm midpiece, principal piece, and acrosome, mediated by projections and sperm agglutination, and resulting in ultrastructural alterations in regions with attached bacteria (Figure 1) [39].…”

O-serotyping of Escherichia coli Strains isolated from Patients With Urinary Tract Infection in Southeast of Iran

“…Urinary tract infection (UTI) is one of the most common infections and Escherichia coli is so far the most common causative agent of this disease (1)(2)(3)(4)(5). O antigen is exposed on the very outer surface of bacterial cell (6)(7)(8) and is an essential component of the lipopolysaccharides on the surface of Gram-negative bacteria; its variation provides a major basis for serotyping schemes (9,10).…”