title: Serotype O18 avian pathogenic and neonatal meningitis Escherichia coli strains employ similar pathogenic strategies for the onset of meningitis.
abstract: Neonatal meningitis Escherichia coli K1 (NMEC) are thought to be transmitted from mothers to newborns during delivery or by nosocomial infections. However, the source of E. coli K1 causing these infections is not clear. Avian pathogenic E. coli (APEC) have the potential to cause infection in humans while human E. coli have potential to cause colibacillosis in poultry, suggesting that these strains may lack host specificity. APEC strains are capable of causing meningitis in newborn rats; however, it is unclear whether these bacteria use similar mechanisms to that of NMEC to establish disease. Using four representative APEC and NMEC strains that belong to serotype O18, we demonstrate that these strains survive in human serum similar to that of the prototypic NMEC strain E44, a derivative of RS218. These bacteria also bind and enter both macrophages and human cerebral microvascular endothelial cells (HCMEC/D3) with similar frequency as that of E44. The amino acid sequences of the outer membrane protein A (OmpA), an important virulence factor in the pathogenesis of meningitis, are identical within these representative APEC and NMEC strains. Further, these strains also require FcγRI-α chain (CD64) and Ecgp96 as receptors for OmpA in macrophages and HCMEC/D3, respectively, to bind and enter these cells. APEC and NMEC strains induce meningitis in newborn mice with varying degree of pathology in the brains as assessed by neutrophil recruitment and neuronal apoptosis. Together, these results suggest that serotype O18 APEC strains utilize similar pathogenic mechanisms as those of NMEC strains in causing meningitis.
authors.affiliation: a Division of Infectious Diseases and Department of Pediatrics; Children's Hospital Los Angeles , CA USA.
authors.forename: Subramanian
authors.initials: S
authors.lastname: Krishnan
authors.affiliation: a Division of Infectious Diseases and Department of Pediatrics; Children's Hospital Los Angeles , CA USA.
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Chang
authors.affiliation: a Division of Infectious Diseases and Department of Pediatrics; Children's Hospital Los Angeles , CA USA.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Hodges
authors.affiliation: b Inserm; Institut Cochin, Paris, France; Université Paris Descartes; Sorbonne Paris Cité , Paris , France.
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Couraud
authors.affiliation: c Department of Life ; Health and Chemical Sciences; Open University ; Milton Keynes , UK.
authors.forename: Ignacio A
authors.initials: IA
authors.lastname: Romero
authors.affiliation: d Division of Hematology and Medical Oncology; Weill Cornell Medical College ; New York , NY USA.
authors.forename: Babette
authors.initials: B
authors.lastname: Weksler
authors.affiliation: e Department of Veterinary Microbiology and Preventive Medicine ; College of Veterinary Medicine; Iowa State University ; Ames , IA USA.
authors.forename: Bryon A
authors.initials: BA
authors.lastname: Nicholson
authors.affiliation: e Department of Veterinary Microbiology and Preventive Medicine ; College of Veterinary Medicine; Iowa State University ; Ames , IA USA.
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Nolan
authors.affiliation: a Division of Infectious Diseases and Department of Pediatrics; Children's Hospital Los Angeles , CA USA.|f Department of Surgery ; Children's Hospital Los Angeles; University of Southern California ; Los Angeles , CA USA.
authors.forename: Nemani V
authors.initials: NV
authors.lastname: Prasadarao
mesh_terms: D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D004926:Escherichia coli / Q000145:classification / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D015870:Gene Expression; D008264:Macrophages / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D020814:Meningitis, Escherichia coli / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010802:Phylogeny; D000067996:RAW 264.7 Cells; D017452:Receptors, IgG / Q000276:immunology; D017422:Sequence Analysis, DNA; D065288:Serogroup; D014774:Virulence
chemical_list: D001425:Bacterial Outer Membrane Proteins; D017452:Receptors, IgG; C078167:OMPA outer membrane proteins
keywords: Escherichia coli K1; endothelial cells; invasion; macrophages; meningitis