Identification and characterization of Escherichia coli RS218-derived islands in the pathogenesis of E. coli meningitis.
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.
Xie
Yi
Y
Division of Pediatric Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Kolisnychenko
Vitaliy
V
Paul-Satyaseela
Maneesh
M
Elliott
Simon
S
Parthasarathy
Geetha
G
Yao
Yufeng
Y
Plunkett
Guy
G
Blattner
Frederick R
FR
Kim
Kwang Sik
KS
D000818:Animals; D016470:Bacteremia / Q000382:microbiology; D001483:Base Sequence; D004926:Escherichia coli / Q000235:genetics* / Q000302:isolation & purification; D005260:Female; D017353:Gene Deletion; D044404:Genomic Islands; D006801:Humans; D008297:Male; D020814:Meningitis, Escherichia coli / Q000382:microbiology*; D008969:Molecular Sequence Data; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000382:microbiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D037521:Virulence Factors / Q000235:genetics
D037521:Virulence Factors