title: Cytotoxic necrotizing factor 1 contributes to Escherichia coli meningitis.
abstract: E. coli is the most common Gram-negative bacteria causing neonatal meningitis, and E. coli meningitis continues to be an important cause of mortality and morbidity throughout the world. Recent reports of E. coli meningitis caused by antimicrobial resistant strains are a particular concern. These findings indicate that a novel strategy is needed to identify new targets for prevention and therapy of E. coli meningitis. Cytotoxic necrotizing factor 1 (CNF1) is a bacterial virulence factor associated principally with E. coli strains causing urinary tract infection and meningitis. We have shown that CNF1 contributes to E. coli invasion of the blood-brain barrier and penetration into the brain, the essential step in the development of E. coli meningitis, and identified the host receptor for CNF1, 37-kDa laminin receptor precursor (37LRP). CNF1, however, is a cytoplasmic protein and its contribution to E. coli invasion of the blood-brain barrier requires its secretion from the bacterial cytoplasm. No signal peptide is found in the CNF1 sequence. CNF1 secretion is, therefore, a strategy utilized by meningitis-causing E. coli to invade the blood-brain barrier. Elucidation of the mechanisms involved in CNF1 secretion, as shown in this report with the involvement of Fdx and YgfZ provides the novel information on potential targets for prevention and therapy of E. coli meningitis by virtue of targeting the secretion of CNF1.
authors.affiliation: Division of Pediatric Urology, Johns Hopkins University School of Medicine, 1800 Orleans Street, Bloomberg, 7308, Baltimore, MD 21287, USA. kwangkim@jhmi.edu.
authors.forename: Ming-Hsien
authors.initials: MH
authors.lastname: Wang
authors.forename: Kwang Sik
authors.initials: KS
authors.lastname: Kim
mesh_terms: D001427:Bacterial Toxins / Q000633:toxicity*; D001812:Blood-Brain Barrier / Q000382:microbiology; D002460:Cell Line; D042783:Endothelial Cells / Q000382:microbiology; D004926:Escherichia coli / Q000472:pathogenicity*; D029968:Escherichia coli Proteins / Q000378:metabolism / Q000633:toxicity*; D017353:Gene Deletion; D006801:Humans; D020814:Meningitis, Escherichia coli / Q000473:pathology* / Q000517:prevention & control; D009154:Mutation; D015398:Signal Transduction; D037521:Virulence Factors / Q000633:toxicity*
chemical_list: D001427:Bacterial Toxins; D029968:Escherichia coli Proteins; D037521:Virulence Factors; C060296:cytotoxic necrotizing factor type 1