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

Severe invasive group A streptococcal diseases have re-emerged during the past 10-20 years. In order to provide a better insight into the current epidemiological situation in France, we analysed the questionnaires regarding all invasive strains received at the National Reference Center for Streptococci (CNR-Strep) between 2006 and 2010 from patients aged ≥ 18 and characterized them by emm typing, spe gene detection and antibiotic resistance. Among the 1542 invasive GAS strains studied, 78% (n=1206) were from blood cultures, and a streptococcal toxic shock syndrome (STSS) was described in 22% (n=340) of cases, mainly associated with necrotizing fasciitis (NF) and pleuro-pulmonary infections (p<0.001). The in-hospital fatality rate was 15%. A total of 83 different emm types were recovered but the three predominant emm types, representing almost 60% of the isolates, were emm1 (24%), emm28 (17%) and emm89 (15%). The preponderance of each emm type varied according to the year, with a significant constant increase of emm28 strains, whereas emm1 strains, representing approximately 32% of GAS invasive isolates in 2007 and 2008, dropped to <15% in 2010 (p<0.001). The distribution of phage-associated superantigen genes (speA, speC and ssa) was linked to certain emm types. Between 2006 and 2010, the percentage that was macrolide-resistant decreased from 11% to 5%, confirming the trend observed in 2007. Fortunately, emm1 strains associated with the most life-threatening clinical manifestations remain susceptible to all anti-streptococcal antibiotics.