Cyclomodulins in Urosepsis Strains of Escherichia coli

Abstract

Determinants of urosepsis in Escherichia coli remain incompletely defined. Cyclomodulins (CMs) are a growing functional family of toxins that hijack the eukaryotic cell cycle. Four cyclomodulin types are actually known in E. coli: cytotoxic necrotizing factors (CNFs), cycle-inhibiting factor (Cif), cytolethal distending toxins (CDTs), and the pks-encoded toxin. In the present study, the distribution of CM-encoding genes and the functionality of these toxins were investigated in 197 E. coli strains isolated from patients with communityacquired urosepsis (n ‫؍‬ 146) and from uninfected subjects (n ‫؍‬ 51). This distribution was analyzed in relation to the phylogenetic background, clinical origin, and antibiotic resistance of the strains. It emerged from this study that strains harboring the pks island and the cnf1 gene (i) were strongly associated with the B2 phylogroup (P, <0.001), (ii) frequently harbored both toxin-encoded genes in phylogroup B2 (33%), and (iii) were predictive of a urosepsis origin (P, <0.001 to 0.005). However, the prevalences of the pks island among phylogroup B2 strains, in contrast to those of the cnf1 gene, were not significantly different between fecal and urosepsis groups, suggesting that the pks island is more important for the colonization process and the cnf1 gene for virulence. pks-or cnf1-harboring strains were significantly associated with susceptibility to antibiotics (amoxicillin, cotrimoxazole, and quinolones [P, <0.001 to 0.043]). Otherwise, only 6% and 1% of all strains harbored the cdtB and cif genes, respectively, with no particular distribution by phylogenetic background, antimicrobial susceptibility, or clinical origin.The bacterial species Escherichia coli comprises a wide diversity of strains belonging to the commensal intestinal flora of humans and warm-blooded animals. Among these strains, several pathogenic variants cause intestinal or extraintestinal infections in humans and animals (33). Population genetic studies based on multilocus enzyme electrophoresis and various DNA markers (10,20,44) classify the E. coli strains into four major phylogenetic groups (A, B1, B2, and D). The groups are diversely associated with certain ecological niches and propensities to cause disease.Extraintestinal pathogenic E. coli (ExPEC) strains are facultative pathogens that are not yet fully described. They are reported to belong mainly to phylogroups B2 and D, and they possess high numbers of virulence genes that belong to a flexible gene pool (43, 53). Among ExPEC strains, uropathogenic E. coli (UPEC) strains take advantage of host behavior and susceptibility by employing virulence factors that facilitate bacterial growth and persistence in the urinary tract (5, 28-30). Important virulence mechanisms are adhesion, invasion, subversion of host defenses, and direct interference with host cellular functions via secreted effectors (33,69).These effectors include the cyclomodulins (CMs), a functional class of toxins that hijack the cell cycle, a fundamental host cell process (48). In the ...

Cytotoxic Escherichia coli strains encoding colibactin colonize laboratory mice

“…E. coli with adherent invasive phenotype has also been isolated from dogs with granulomatous colitis [7]. Furthermore, E. coli strains can be classified into phylogenetic groups (A, B1, B2, and D) and/or subgroups (A0, A1, B1, B22, B23, D1, and D2) which can be used for epidemiological investigations [8–10]. …”

ClbP Is a Prototype of a Peptidase Subgroup Involved in Biosynthesis of Nonribosomal Peptides

“…The pks island was detected in E. coli strains involved in extraintestinal infections such as urinary tract infection and septicemia but also in commensal strains from healthy people (3,5,6). The genetic and functional analyses of the pks island indicate that it encodes for synthesis of a PK-NRP hybrid compound, named colibactin.…”

Deamidase toxins

“…This Rac1-dependent production of ROS that is controlled by HACE1 leads to an enhanced cellular proliferation and the induction of DNA damage responses that may contribute to the accumulation of oncogenic mutations [75]. Rac1-activating toxins are highly prevalent in the pathogenic E. coli group B2 [11,76]. These toxins are referred to as cyclomodulin because they deregulate the cell cycle and may contribute to colorectal cancer initiation, progression, or both.…”

“…Both these toxins are synthesized as single polypeptides of approximately 110 kDa. The CNF1 encoding gene is highly prevalent in uropathogenic strains of E. coli, typically those within the phylogenic group B2 [11,12]. The cnf1 gene is downstream of the alpha-hemolysin CABD operon and forms a single giant operon.…”