A new O-antigen gene cluster has a key role in the virulence of the Escherichia coli meningitis clone O45:K1:H7.
ABSTRACT A new highly pathogenic clone of Escherichia coli meningitis strains harboring the unusual serogroup O45 has recently emerged in France. To gain insight into the pathogenicity of this new clone, we investigated the possible role of antigen O45 in the virulence of strain S88 (O45:K1:H7), representative of this emerging clone. We first showed that the S88 O-antigen gene cluster sequence differs from that of O45 in the reference strain E. coli 96-3285, suggesting that the two O45 polysaccharides, while probably sharing a community of epitopes, represent two different antigens. The unique functional organization of the two O-antigen gene clusters and the low DNA sequence homology of the orthologous genes suggest that the two loci originated from a common ancestor and have since undergone multiple recombination events. Phylogenetic analysis based on the flanking gene gnd sequences indicates that the S88 antigen O45 (O45(S88)) gene cluster may have been acquired, at least in part, from another member of the Enterobacteriaceae. Mutagenesis of the O45(S88) antigen gene cluster was used for functional analysis of the loci and revealed the crucial role of the O polysaccharide in S88 virulence in a neonatal rat meningitis model. We also developed a PCR method to specifically identify the O45(S88) antigen gene cluster. Together, our findings suggest that horizontal acquisition of a new O-antigen gene cluster, at least partly from another species, may have been a key event in the emergence and virulence of the E. coli O45:K1:H7 clone in France.
Article: Comparative prevalence of virulence factors in Escherichia coli causing urinary tract infection in male infants with and without bacteremia.[show abstract] [hide abstract]
ABSTRACT: Escherichia coli isolates causing urinary tract infection in 83 male infants younger than 90 days with and without bacteremia were compared for phylogenetic groups and the presence of 10 virulence factors. Our result suggest that the absence of both hemolysin and antigen K1 may be used as a negative predictive factor for bacteremia.Journal of Clinical Microbiology 04/2006; 44(3):1156-8. · 4.15 Impact Factor
Article: Molecular analysis and experimental virulence of French and North American Escherichia coli neonatal meningitis isolates: identification of a new virulent clone.[show abstract] [hide abstract]
ABSTRACT: Phylogenetic relationships, virulence factors, alone and in specific combinations, and virulence in a rat meningitis model were examined among 132 isolates of Escherichia coli neonatal meningitis from France and North America. Isolates belonging to phylogenetic groups A (n=11), D (n=20), and B2 (n=99) had similar high prevalence rates of the siderophores aerobactin and yersiniabactin and the K1 capsule (>/=70%) yet induced different level of experimental bacteremia. Ectochromosomal DNA-like domains involved in blood-brain barrier passage (PAI III(536) [sfa/foc and iroN; 34%]; GimA [ibeA and ptnC; 38%]; PAI II(J96) [hly, cnf1, and hra; 10%]) were restricted to B2 isolates. Among group B2 isolates, representatives of the O45:K1 clonal group (n=30), which lacked these domains, were as able as the archetypal O18:K1 strain C5 to cause meningitis. Molecular epidemiology combined with experimental virulence assays demonstrate that known virulence factors are insufficient to fully explain the pathophysiology of ECNM and to allow for rational search for new virulence factors.The Journal of Infectious Diseases 06/2003; 187(12):1895-906. · 6.41 Impact Factor
Article: The K1 capsule is the critical determinant in the development of Escherichia coli meningitis in the rat.[show abstract] [hide abstract]
ABSTRACT: Although Escherichia coli strains possessing the K1 capsule are predominant among isolates from neonatal E. coli meningitis and most of these K1 isolates are associated with a limited number of 0 lipopolysaccharide (LPS) types, the basis of this association of K1 and certain 0 antigens with neonatal E. coli meningitis is not clear. The present study examined in experimental E. coli bacteremia and meningitis in newborn and adult rats whether or not the K1 capsule and/or O-LPS antigen are critical determinants in the development of meningitis. Rats received subcutaneously at K1 E. coli strain (018+K1+) or mutants lacking either the K1 capsule (018+K1-) or 0 side-chain (018-K1+). 12-24 h later, blood and cerebrospinal fluid (CSF) specimens were obtained for quantitative cultures. The isolation of E. coli from CSF was observed in both newborn and adult rats infected with K1+ strains regardless of LPS phenotype (018+ or 18-) who also developed a high degree of bacteremia (e.g., greater than 10(4) CFU/ml of blood). In contrast, none of the newborn and adult rats infected with 018+K1- and developing bacteremia of greater than 10(4) were found to have positive CSF cultures. These findings indicate that the presence of the K1 capsule and a high degree of bacteremia are key determinants in the development of E. coli meningitis, suggesting that there may be specific binding sites present in the brain which have an affinity for the K1 capsule and thus may be responsible for the entry of K1-encapsulated E. coli into the meninges.Journal of Clinical Investigation 10/1992; 90(3):897-905. · 15.39 Impact Factor