title: Extracellular loops of the Eschericia coli outer membrane protein A contribute to the pathogenesis of meningitis.
abstract: Neonatal meningitis by Eschericia coli RS218 occurs due to bacteremia and its transmigration across the blood-brain barrier. Although the outer membrane protein A (OmpA), a molecule with extracellular loops has been shown to contribute to the above phenomenon, we do not know the exact the role of these individual loops. Using bacterial strains whose individual loops have been removed, we demonstrated that whereas Loops1 and 2 contribute to 70%-80% bacterial survival in serum, bacterial entry into human brain microvascular endothelial cells (HBMEC) is governed by Loops1, 2, and 3. Cellular invasion was shown to require activation of host cytosolic phospholipase A2 (cPLA2α) by Loops1 and 2 but not 3. This suggests 2 distinct pathways for bacterial entry into host cells. Loop 4 played no role in either serum survival, cellular entry, or cPLA2α signaling. These findings demonstrate for the first time the different contributions of extracellular loops of OmpA to the pathogenesis of E. coli meningitis.
authors.affiliation: Division of Infectious Diseases, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. rmaruva1@jhmi.edu
authors.forename: Ravi
authors.initials: R
authors.lastname: Maruvada
authors.forename: Kwang Sik
authors.initials: KS
authors.lastname: Kim
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D001770:Blood Bactericidal Activity; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000382:microbiology; D004926:Escherichia coli / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000382:microbiology; D054513:Group IV Phospholipases A2 / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D007231:Infant, Newborn; D016920:Meningitis, Bacterial / Q000382:microbiology; D050296:Microbial Viability; D017384:Sequence Deletion; D044967:Serum / Q000382:microbiology; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D037521:Virulence Factors; C078167:OMPA outer membrane proteins; D054513:Group IV Phospholipases A2