A new Escherichia coli virulent clonal group, O45:K1, belonging to the highly virulent subgroup B2 1 was recently identified in France, where it accounts for one-third of E. coli neonatal meningitis cases. Here we describe the sequence, epidemiology and function of the large plasmid harbored by strain S88, which is representative of the O45:K1 clonal group. Plasmid pS88 is 133,853 bp long and contains 144 protein-coding genes. It harbors three different iron uptake systems (aerobactin, salmochelin, and the sitABCD genes) and other putative virulence genes (iss, etsABC, ompT P , and hlyF). The pS88 sequence is composed of several gene blocks homologous to avian pathogenic E. coli plasmids pAPEC-O2-ColV and pAPEC-O1-ColBM. PCR amplification of 11 open reading frames scattered throughout the plasmid was used to investigate the distribution of pS88 and showed that a pS88-like plasmid is present in other meningitis clonal groups such as O18:K1, O1:K1, and O83:K1. A pS88-like plasmid was also found in avian pathogenic strains and human urosepsis strains belonging to subgroup B2 1 . A variant of S88 cured of its plasmid displayed a marked loss of virulence relative to the wild-type strain in a neonatal rat model, with bacteremia more than 2 log CFU/ml lower. The salmochelin siderophore, a known meningovirulence factor, could not alone explain the plasmid's contribution to virulence, as a salmochelin mutant displayed only a minor fall in bacteremia (0.9 log CFU/ml). Thus, pS88 is a major virulence determinant related to avian pathogenic plasmids that has spread not only through meningitis clonal groups but also human urosepsis and avian pathogenic strains.Escherichia coli is the second cause of neonatal bacterial meningitis in industrialized countries, after group B streptococci. Despite advances in neonatal care, E. coli neonatal meningitis (ECNM) remains a potentially devastating illness, with a mortality rate of 10 to 15% and neurological sequelae in 30 to 50% of cases (8,20,28,29,62). Like most extraintestinal pathogenic E. coli (ExPEC) strains, ECNM strains mainly belong to phylogenetic group B2 and compose a small number of

The genetic relatedness of 223 invasive Escherichia coli strains that cause either meningitis or urosepsis without meningitis in young infants was determined by multilocus sequence typing (MLST), ribotyping, and phylogenetic polymerase chain reaction grouping. We also determined the serotypes and virulence genotypes (on the basis of 11 virulence genes). The strains belonged to 29 sequence type complexes (STc), 20 ribotypes, 26 O serogroups, and 39 virulence genotypes. MLST combined with O serogrouping identified 49 subtypes, or "sequence O types." Some sequence O types were almost exclusively associated with either urosepsis (STc27(O2), STc27(O6), and STc29(O2)) or meningitis (STc29(O18)). In contrast, STc29(O45) was equally frequent in these 2 infection sites. Similarly, several virulence genotypes were specifically associated with one of these syndromes. These results point to the existence of specialized invasive subtypes that cause urosepsis or meningitis in infants and identify a new dually virulent invasive clone.

Escherichia coli bacteremia in young infants may arise via either urinary tract infection or gut translocation (GT). E. coli GT isolates have rarely been investigated. Molecular analysis of 100 E. coli isolates recovered from bacteremic infants revealed that GT isolates had multilocus sequence types similar to those of urosepsis isolates but different prevalences of PapGII adhesin, TcpC protectin, and ibeA invasin. Compared with late-onset GT isolates, early-onset isolates were associated with significantly different rates of the conserved virulence plasmidic region common to human and avian pathogenic strains and α-hemolysin. We identified genetic determinants potentially involved in specific pathophysiological steps preceding E. coli bloodstream invasion.