TY - JOUR
T1 - Identification and characterization of Escherichia coli RS218-derived islands in the pathogenesis of E. coli meningitis
AU - Xie, Yi
AU - Kolisnycheiko, Vitaliy
AU - Paul-Satyasesla, Maneesh
AU - Elliott, Simon
AU - Parthasarathy, Geetha
AU - Yao, Yirfeng
AU - Plunkett, Guy
AU - Blattner, Frederick R.
AU - Kim, Kwang Sik
N1 - Funding Information:
Received 16 November 2005; accepted 8 March 2006; electronically published 30 June 2006. Presented in part: 105th Annual General Meeting of the American Society for Microbiology, Atlanta, Georgia, 6–8 June 2005 (poster B136). Potential conflicts of interest: none reported. Financial support: National Institutes of Health (grants RO1-NS 26310 and AI 47225). aY.X., V.K., and M.P.-S. contributed equally to the study. Reprints or correspondence: Dr. Kwang Sik Kim, Div. of Pediatric Infectious Diseases, Johns Hopkins University School of Medicine, 600 N. Wolfe St., Park 256, Baltimore, MD 21287 (kwangkim@jhmi.edu).
PY - 2006/8/1
Y1 - 2006/8/1
N2 - Background. Escherichia coli K1 is the most common gram-negative bacterium causing neonatal meningitis, but the mechanisms by which E. coli K1 causes meningitis are not clear. Methods. We identified 22 E. coli RS218-derived genomic islands (RDIs), using a comparative genome analysis of meningitis-causing E. coli K1 strain RS218 (O18:K1:H7) and laboratory K-12 strain MG1655. Series of RDI deletion mutants were constructed and examined for phenotypes relevant to E. coli K1 meningitis. Results. We identified 9 RDI deletion mutants (RDI 1, 4, 7, 12, 13, 16, 20, 21, and 22) that exhibited defects in meningitis development. RDI 16 and 21 mutants had profound defects in the induction of a high level of bacteremia in neonatal rats, and RDI 4 mutants exhibited a moderate defect in the induction of bacteremia. RDI 1 and 22 mutants showed defects in the ability to invade human brain microvascular endothelial cells (HBMECs), and RDI 12 mutants were defective in the ability to bind to HBMECs. RDI 13 and 20 mutants were defective in the ability to both bind to and invade HBMECs. RDI 7 mutants were defective in the induction of bacteremia and in the ability to both bind to and invade HBMECs. Conclusions. These results provide a framework for the future discovery and analysis of bacteremia and meningitis caused by E. coli K1 strain RS218.
AB - Background. Escherichia coli K1 is the most common gram-negative bacterium causing neonatal meningitis, but the mechanisms by which E. coli K1 causes meningitis are not clear. Methods. We identified 22 E. coli RS218-derived genomic islands (RDIs), using a comparative genome analysis of meningitis-causing E. coli K1 strain RS218 (O18:K1:H7) and laboratory K-12 strain MG1655. Series of RDI deletion mutants were constructed and examined for phenotypes relevant to E. coli K1 meningitis. Results. We identified 9 RDI deletion mutants (RDI 1, 4, 7, 12, 13, 16, 20, 21, and 22) that exhibited defects in meningitis development. RDI 16 and 21 mutants had profound defects in the induction of a high level of bacteremia in neonatal rats, and RDI 4 mutants exhibited a moderate defect in the induction of bacteremia. RDI 1 and 22 mutants showed defects in the ability to invade human brain microvascular endothelial cells (HBMECs), and RDI 12 mutants were defective in the ability to bind to HBMECs. RDI 13 and 20 mutants were defective in the ability to both bind to and invade HBMECs. RDI 7 mutants were defective in the induction of bacteremia and in the ability to both bind to and invade HBMECs. Conclusions. These results provide a framework for the future discovery and analysis of bacteremia and meningitis caused by E. coli K1 strain RS218.
UR - http://www.scopus.com/inward/record.url?scp=33746367171&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33746367171&partnerID=8YFLogxK
U2 - 10.1086/505429
DO - 10.1086/505429
M3 - Article
C2 - 16826484
AN - SCOPUS:33746367171
SN - 0022-1899
VL - 194
SP - 358
EP - 364
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 3
ER -