Role of Deoxyribose Catabolism in Colonization of the Murine Intestine by PathogenicEscherichia coliStrains

Abstract

We previously suggested that the ability to metabolize deoxyribose, a phenotype encoded by the deoK operon, is associated with the pathogenic potential of Escherichia coli strains. Carbohydrate metabolism is thought to provide the nutritional support required for E. coli to colonize the intestine. We therefore investigated the role of deoxyribose catabolism in the colonization of the gut, which acts as a reservoir, by pathogenic E. coli strains. Molecular and biochemical characterization of 1,221 E. coli clones from various collections showed this biochemical trait to be common in the E. coli species (33.6%). However, multivariate analysis evidenced a higher prevalence of sugar-metabolizing E. coli clones in the stools of patients from countries in which intestinal diseases are endemic. Diarrhea processes frequently involve the destruction of intestinal epithelia, so it is plausible that such clones may be positively selected for in intestines containing abundant DNA, and consequently deoxyribose. Statistical analysis also indicated that symptomatic clinical disorders and the presence of virulence factors specific to extraintestinal pathogenic E. coli were significantly associated with an increased risk of biological samples and clones testing positive for deoxyribose. Using the streptomycintreated-mouse model of intestinal colonization, we demonstrated the involvement of the deoK operon in gut colonization by two pathogenic isolates (one enteroaggregative and one uropathogenic strain). These results, indicating that deoxyribose availability promotes pathogenic E. coli growth during host colonization, suggest that the acquisition of this trait may be an evolutionary step enabling these pathogens to colonize and persist in the mammalian intestine.Escherichia coli is a normal inhabitant of the intestines of healthy individuals. However, under certain circumstances, E. coli can also be a serious pathogen in humans and animals. Many studies over the last 30 years have focused on the identification and description of numerous virulence factors and the genes encoding them. There is now a substantial body of knowledge concerning the development of three major clinical syndromes caused by these bacteria: urinary tract infections (UTI), sepsis/meningitis, and diarrhea. The strains causing the extraintestinal diseases are referred to as ExPEC (extraintestinal pathogenic E. coli) strains and include uropathogenic E. coli and sepsis/meningitis-associated E. coli strains. The intestinal pathogens are distributed into at least six well-described pathovars-enteropathogenic E. coli, Shiga toxin-producing E. coli, enterotoxigenic E. coli, enteroinvasive E. coli, enteroaggregative E. coli (EAEC), and diffusely adherent E. coliwhich exhibit differing physiopathological behavior patterns (33, 41). The reservoir for all pathogenic E. coli strains is the gut, and it remains unclear how pathogenic E. coli strains outcompete the gut microflora to colonize the mammalian intestine and how they survive in this complex ecosystem. Increasin...

Role of the Vpe Carbohydrate Permease in Escherichia coli Urovirulence and Fitness In Vivo

“…This gene was present in 48.15% of pathogenic isolates (52/108) and 15% of commensal strains (19/127); this difference was found to be significant (P Ͻ 0.0001) in 2 analysis. The presence and expression of the deoK operon had previously been investigated in all the strains of the collection (32). For confirmation of the linkage of the two loci observed during genome comparison, we amplified the region between the vpeC and deoM genes by PCR with the vpeC-F and deoM-F primers (see Tables S1 and S2 in the supplemental material and Fig.…”

“…In most cases, the vpe and deoK loci are strongly linked (Ͼ75% association). We previously showed that the deoK operon encodes proteins involved in deoxyribose utilization and was acquired by horizontal transfer from Salmonella enterica (6,32). The high level of similarity between the vpe locus and a chromosomal sequence in Yersinia (75% identical to the sequence of Y. enterocolitica strain 8081) and its GϩC content of 46.8% suggested that E. coli acquired this sequence from Yersinia.…”

“…We studied 235 well-characterized clinical isolates from our laboratory collection (32), including 88 isolates obtained from the urine or blood of patients, 20 enteroaggregative E. coli (EAEC) strains, and 127 E. coli isolates obtained from the stool samples of healthy subjects. Isolate AL511 was used as the prototype for characterization of the genes of interest (Table 1).…”

“…The intestine-colonizing abilities of the AL511 strain and its vpe derivative were compared in a previously described competition-based model (32) in streptomycin-treated BALB/c female mice (7 weeks old; Janvier Laboratories). After 18 to 20 h of food and water starvation, the mice were fed 200 l of a sucrose (20%)-bicarbonate (2.6%) solution supplemented with 10 5 to 10 6 CFU of bacteria grown overnight in LB broth with shaking.…”

“…The catabolism of deoxyribose is catalyzed by the products of the deoK operon, which has been transferred from Salmonella enterica to E. coli (6). Using a mouse model of intestinal colonization, we recently demonstrated the involvement of this operon in gut colonization by pathogenic E. coli strains, including a UPEC strain (32). The deoK operon is frequently associated with strains isolated from infected urine and blood, in which it is always located in large specific islands carrying genes contributing to the intrinsic virulence and/or adaptive properties of the strain.…”