Affiliation:
1. Division of Infectious Diseases, Childrens Hospital Los Angeles,1 and
2. Keck School of Medicine, University of Southern California,2 Los Angeles, California 90027
Abstract
ABSTRACT
Neonatal
Escherichia coli
meningitis remains a devastating disease, with unacceptably high morbidity and mortality despite advances in supportive care measures and bactericidal antibiotics. To further our ability to improve the outcome of affected neonates, a better understanding of the pathogenesis of the disease is necessary. To identify potential bacterial genes which contribute to
E. coli
invasion of the blood-brain barrier, a cerebrospinal fluid isolate of
E. coli
K1 was mutagenized with Tn
phoA
. Tn
phoA
mutant 27A-6 was found to have a significantly decreased ability to invade brain microvascular endothelial cells compared to the wild type. In vivo, 32% of the animals infected with mutant 27A-6 developed meningitis, compared to 82% of those infected with the parent strain, despite similar levels of bacteremia. The DNA flanking the Tn
phoA
insertion in 27A-6 was cloned and sequenced and determined to be homologous to
E. coli
K-12
aslA
(arylsulfatase-like gene). The deduced amino acid sequence of the
E. coli
K1
aslA
gene product shows homology to a well-characterized arylsulfatase family of enzymes found in eukaryotes, as well as prokaryotes. Two additional
aslA
mutants were constructed by targeted gene disruption and internal gene deletion. Both of these mutants demonstrated decreased invasion phenotypes, similar to that of Tn
phoA
mutant 27A-6. Complementation of the decreased-invasion phenotypes of these mutants was achieved when
aslA
was supplied in
trans
. This is the first demonstration that this locus contributes to invasion of the blood-brain barrier by
E. coli
K1.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
80 articles.
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