Colonization with Escherichia coli Strains among Female Sex Partners of Men with Febrile Urinary Tract Infection

Abstract

Of 23 unique Escherichia coli strains from 10 men with febrile urinary tract infections (UTIs) and their female sex partners, 6 strains (all UTI causing) were shared between partners. Molecularly, the 6 shared strains appeared more virulent than the 17 nonshared strains, being associated with phylogenetic group B2, sequence types ST73 and ST127, and multiple specific virulence genes. This indicates that UTIs are sometimes sexually transmitted.

TEXT

Escherichia coli is the leading cause of urinary tract infection (UTI), a tremendously common and costly illness (1). Although the causative E. coli strains usually derive from the host's own gastrointestinal microbiota (2, 3), their more proximate reservoirs are poorly understood.

Sharing of E. coli strains, whether pathogenic or not, is common among closely associated hosts, including pets and sex partners (4–19). However, strain sharing between a man with an E. coli UTI and his healthy female sexual partner (FSP) has not been reported. We capitalized on a large cohort of men with E. coli febrile UTIs (FUTIs) to assess this phenomenon's frequency and the characteristics of any shared strains.

Subjects and specimens.

Ten men with community-acquired E. coli FUTI and an FSP who was willing to participate in the study were identified within a larger cohort study of male FUTI at Sahlgrenska University Hospital, Gothenburg, Sweden, from 1993 to 1996 (21, 22). Men had to have a temperature of ≥ 38.0°C, at least one urinary tract-referable symptom or sign (e.g., frequency, dysuria, flank pain, or costovertebral angle tenderness), and ≥10⁴ CFU/ml of a uropathogen on urine culture (21, 22). Consenting subjects underwent culture surveillance of urine, feces, and (for FSPs) the vagina initially and with any subsequent UTI episode in either partner.

Midstream urine samples, collected per protocol, were kept at 4°C until cultured semiquantitatively on blood and cysteine lactose electrolyte-deficient agar. Significant growth was defined as ≥10⁴ CFU/ml of E. coli. The last free-lying colony was saved.

Men self-collected rectal samples per protocol. One of the authors (P.U.) collected vaginal and rectal samples from FSPs. Swabs were streaked to modified Conradi-Drigalski agar for overnight incubation. The last three free-lying colonies on each plate, plus any morphologically distinct colonies, were picked for analysis; this provided ≥97% sensitivity for detecting the quantitatively predominant clone in rectal samples (23). Confirmed E. coli isolates were stored in agar stabs (24).

Isolate characterization.

E. coli isolates underwent O typing or full O:K:H serotyping at Statens Serum Institute, Copenhagen, Denmark. One colony per O:K:H serotype per specimen, and colonies differing by O type from the index FUTI isolate, underwent molecular typing, including XbaI pulsed-field gel electrophoresis (PFGE) profiling (25). Pulsotypes (herein equated with strains) were assigned based on ≥94% profile similarity to index profiles within a large PFGE database (26).

One representative per sample per PFGE type underwent PCR-based major phylogenetic group determination (25). Extended virulence genotypes were determined by multiplex PCR (27–29). Sequence type (ST) and clonal complex (CC; cluster of closely related STs) were determined by PCR (27), fumC-fimH sequence analysis (30), and/or multilocus sequence typing (http://mlst.warwick.ac.uk).

Statistical methods.

Comparisons of proportions and virulence score were tested using Fisher's exact test and the Mann-Whitney U test, respectively, with significance set at a P value of <0.05.

Study population.

The 10 index men with FUTI had a median age of 55 years (range, 37 to 69 years) and a median temperature of 39.3°C (range, 39.0°C to 40.5°C) (see Table S1 in the supplemental material). None affirmed anal intercourse during the preceding 6 months. Two patients had voiding problems suggestive of prostatism. Only 3 had possible UTI-predisposing conditions, including postoperative urethral catheterization 3 days pre-FUTI episode, diabetes mellitus, and a small bladder adenoma. The median age of the 10 FSPs was 48.5 years (range, 32 to 62 years). All of the FSPs denied UTI symptoms and antibiotic treatment in the preceding 3 months.

Culture results.

Culture surveillance was done once for 7 couples and repeatedly (over 1 to 22 months) for 3 couples. Of the 76 total rectal, vaginal, and urine cultures, 59 (78%) yielded E. coli. Sequential serotyping and PFGE analysis resolved 23 unique E. coli strains (Fig. 1), which were predominantly from phylogroup B2 (12 strains [52%]) and represented 15 CCs. Seventeen strains (74%) qualified molecularly as extraintestinal pathogenic E. coli (ExPEC).

FIG 1.

Pulsed-field gel electrophoresis (PFGE) profiles of Escherichia coli isolates from 10 men with febrile urinary tract infection and their female sex partners. Dendrogram is based on pairwise similarity relationships among XbaI PFGE profiles, as reflected in Dice similarity coefficients. Colored rectangles enclose profiles of the same pulsotype. Labels to right of dendrogram show the couple number. PFGE column lists pulsotype designation, which is also shown to the right of each rectangle for shared strains. Red circle identifies the sole instance of putative strain sharing across couples (couple 29 versus couple 95), which likely was spurious (based on differences in virulence genotype).

Strain sharing.

Of the 23 strains, 6 occurred in both members of a particular couple and only in that couple (Fig. 1). All 6 (100%) shared strains, versus 4 (24%) nonshared strains, represented the male's index FUTI isolate (P = 0.002) (Table 1). Shared strains also were more likely to cause asymptomatic bacteriuria (ABU) or acute cystitis and to colonize the woman's rectum and/or vagina.

TABLE 1.

Colonization and clinical characteristics of 23 Escherichia coli strains from 10 men with FUTI and their female sexual partners in relation to strain sharing

Characteristic	Prevalence of characteristic (no. [column %])			P value, nonshared vs shareda
	Total (n = 23)	Nonshared strains (n = 17)	Shared strains (n = 6)
Male, any site	18 (78)	12 (71)	6 (100)
Rectum	11 (48)	10 (59)	1 (17)
FUTIb	10 (44)	4 (24)	6 (100)	0.002
ABUc during follow-up	2 (9)	0 (0)	2 (33)	0.06
Female, any site	11 (48)	5 (29)	6 (100)	0.005
Rectum	10 (44)	5 (29)	5 (83)	0.052
Vagina	4 (17)	0 (0)	4 (67)	0.002
Acute cystitis during follow-up	1 (4)	0 (0)	1 (17)
ABU during follow-up	2 (9)	0 (0)	2 (33)	0.06

^aP values (by Fisher's exact test) are shown when they are <0.10.

^bFUTI, febrile urinary tract infection.

^cABU, asymptomatic bacteriuria.

Longitudinal follow-up.

During serial surveillance, the shared strains caused sustained cocolonization and recurrent symptomatic UTI and/or ABU in two couples (couples 10 and 29; see Tables S2 and S3 in the supplemental material). In couple 95, at the time of the man's E. coli FUTI episode, the FSP was colonized extensively with the index E. coli strain, which persisted in her 3 weeks later, despite being undetectable in the man.

Characteristics of shared strains.

Compared with nonshared strains, the 6 shared strains more often represented phylogroup B2 and uropathogenic lineages CC73 or CC127 and more often contained papG III, sfa/foc, sfaS, hlyD, cnf1, iroN, and malX (see Table S4 in the supplemental material).

Comment.

This in-depth microbiological survey of 10 men with E. coli FUTI and their healthy FSPs identified frequent (60%) cocolonization of FSPs with the male partner's index E. coli strain. This equals or exceeds the prevalence of such cocolonization among male partners of women with E. coli cystitis (5, 11, 12).

Such strain sharing may result from person-to-person transmission or parallel acquisition. Cocolonization between sex partners has been associated with specific sex practices (12). We lacked data regarding sexual practices other than anal intercourse (which our subjects denied), so we cannot comment on behavioral correlates of cocolonization.

The potential clinical implications of cocolonization include risks of (i) acute UTI in an FSP due to the male partner's UTI strain and (ii) reintroduction of the strain into the index subject from a cocolonized partner. The first scenario occurred here (couple 10). Whether decolonization of cocolonized sex partners is warranted deserves study.

As in previous studies (6, 7, 12, 31), shared strains were distributed more broadly, caused more infections, and exhibited more uropathogenic traits than did nonshared strains. This indicates that certain E. coli traits and lineages promote both UTI pathogenesis and intestinal colonization (32). Conceivably, interventions directed toward these traits and/or lineages may prevent UTI by blocking both processes.

Since we investigated middle-aged male FUTI patients without serious medical or urological compromise and their middle-aged FSPs, our results cannot be extrapolated to other forms of UTI or host populations. Additionally, since our rectal sampling method detected mainly dominant fecal E. coli clones (23), we likely underestimated the true frequency of cocolonization (33).

Summary.

We demonstrated frequent sharing of the causative E. coli strain between men with FUTI and their FSPs, which indicates that male UTI is sometimes sexually transmitted. Strain sharing was more common and extensive for classic urovirulent strains, suggesting that urovirulence traits may also promote colonization and transmission.