Prevalence of Virulence Genes and Clonality in Escherichia coli Strains That Cause Bacteremia in Cancer Patients

Abstract

Phenotypic analysis of Escherichia coli strains causing bacteremia in cancer patients suggests that they possess specific virulence properties. To investigate this hypothesis, we compared the frequency of the virulence-related genes cnf1, cnf2, papC, hlyC, and iut in 155 E. coli strains isolated from hospitalized cancer patients with epidemiologically unrelated cases of bacteremia to their frequency in 70 E. coli strains isolated from the feces of healthy unrelated volunteers. Of the blood isolates, 24, 37, and 26% were positive for cnf1, papC, and hlyC, respectively, versus only 6, 17, and 6% of the fecal isolates (P < 0.05 in all instances). By contrast, 47% of both isolates carried the iut gene. The patients' clinical characteristics did not significantly influence these frequencies. The presence on various pathogenicity islands (PAIs) of a combination of the cnf1, papC, and hlyC genes on the chromosome was strongly suggested by Southern blotting of pulsed-field gel electrophoresis (PFGE) patterns with specific DNA probes. The phylogenetic relatedness among 60 strains carrying three, two, one, or no virulence genes and 6 ECOR strains included as references was determined by neighbor joining, the unweighted pair-group method with arithmetic mean, and Wagner analysis of the randomly amplified polymorphic DNA (RAPD) patterns generated by 11 primers. Identification of a major cluster including 96.4% of the strains carrying the cnf1, papC, and hlyC genes and ECOR subgroup B2 strains suggested that the virulent E. coli strains causing bacteremia in cancer patients are closely related to ECOR B2 strains. The presence in the E. coli population surveyed of a strong linkage disequilibrium, and especially of a highly significant correlation between PFGE and RAPD genetic distances, confirms that clonal propagation has a major impact on the E. coli population structure. Nevertheless, low bootstrap values in the phylogenetic tree suggested that frequent genetic exchange inhibits the individualization of discrete genetic lineages, which are stable on an evolutionary scale.Patients with cancer are highly susceptible to bacterial infections, particularly during the periods of severe neutropenia that follow anticancer chemotherapy. Bloodstream infections caused by gram-negative bacteria are among the most frequent of these infections and are associated with a high mortality rate (1). Most of the gram-negative bacteria that cause these bloodstream infections originate in the intestinal flora (55) and reach the blood by a mechanism called bacterial translocation (for a review, see reference 4). In experimental models, bacterial translocation is enhanced by intestinal colonization and overgrowth of the translocating bacteria, by immunosuppression of the host, and by alterations of the intestinal mucosa (for a review, see reference 4), all of which may occur in cancer patients.Escherichia coli is the most common gram-negative species isolated from cancer patients with bacteremia (1, 55). Phenotypic studies performed on a series of...

Commensal Escherichia coli isolates are phylogenetically distributed among geographically distinct human populations

“…The strains from Mali harboured fewer virulence factors than did the Croatian (U-test, P l 0n005) and French (U-test, P l 0n0039) isolates, as only one Malian strain (B2 group) possessed two virulence factors versus 23 strains in Croatia and 19 strains in France. These data are consistent with most studies on the frequency of virulence factors in strains from healthy human stools (Minshew et al, 1978 ;Hagberg et al, 1981 ;Goullet & Picard, 1986b ;Opal et al, 1990 ;Siitonen, 1992 ;Hilali et al, 2000). The frequent occurrence of commensal strains with virulence determinants reported by Mu$ hldorfer et al (1996) may be due to a local epidemiological bias, as no such prevalence was found by these workers in Peru (Hacker et al, 1983).…”

“…This absence of difference was also found for each virulence gene (Table 3). In addition, confirming that the strains of phylogenetic group B2 are more frequent among extraintestinal pathogenic strains (40-72 %) than among commensal strains (9-11 %) (Goullet & Picard, 1986b ;Johnson et al, 1991 ;Bingen et al, 1998 ;Picard et al, 1999 ;Hilali et al, 2000 ; this work), our homogeneous dataset also increases our understanding of the emergence of virulence in human extraintestinal infections. The smaller number of virulence determinants in commensal strains of phylogenetic groups A, B1 and D than in the corresponding pathogenic strains is consistent with the hypothesis (Bingen et al, 1998 ;Lecointre et al, 1998 ;Picard et al, 1999) that these strains acquire virulence factors by horizontal transfer, enabling them to become virulent and to invade immunocompetent hosts (Picard & Goullet, 1988) from the host's intestinal reservoir.…”

Extended Virulence Genotype of Pathogenic Escherichia coli Isolates Carrying the afa-8 Operon: Evidence of Similarities between Isolates from Humans and Animals with Extraintestinal Infections

“…Bloodstream infections in which the bacteria are derived from the intestinal flora by bacterial translocation are common in patients with cancer. Preliminary results showed that the afa-8 operon is found in CNF1-producing strains associated with this type of bacteremia (22,38,42). Therefore, afa-8 is probably involved in the development of extraintestinal infections associated with primary colonization of the intestine.…”

“…The virulence potential of ExPEC is determined largely by the presence of specialized VFs, which can be located on large plasmids or on the chromosomes of pathogenic strains. Recognized VFs of ExPEC, which are infrequent among commensal strains, include adhesins (P, S, and F1C fimbriae and Afa-related adhesins), toxins (hemolysin and cytotoxic-necrotizing factor 1), siderophores (aerobactin and yersiniabactin), capsules (K1, K5, and K12), invasins (Ibe10 and afaD genes), and factors contributing to serum resistance (5,22,28,55). Most VF genes are located on PAIs, which are large segments of chromosomal DNA inserted within or near tRNA genes.…”

Comparison of extended spectrum β-lactamases-producingEscherichia coliwith non-ESBLs-producingE.coli: drug-resistance and virulence

“…[1] The deadly E.coli outbreak killed persons and spread across Europe in May 2011. Multidrugresistant E. coli (MDR-ECO) strains have increased with the application of broad-spectrum antibiotics.…”