Pathogenesis of bacterial meningitis: from bacteraemia to neuronal injury

Kim, Kwang Sik

doi:10.1038/nrn1103

Cited by 366 publications

(479 citation statements)

References 94 publications

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“…meningitis in our laboratory [2][3][4][5]. These efforts indicate that a large number of bacterial virulence determinants are involved in the E. coli K1 traversal of the blood-brain barrier, such as K1 capsule, O-LPS, OmpA, Ibe proteins, AslA, TraJ, and CNF1 [1,6].…”

Section: Introductionmentioning

confidence: 88%

“…The blood-brain barrier is characteristic for its tight junctions and high transendothelial electrical resistance, and is highly efficient in blocking the entrance of bacteria into the central nervous system [1]. There are only a limited number of pathogens capable of crossing this barrier and causing meningitis.…”

Section: Introductionmentioning

confidence: 99%

“…Escherichia coli K1 is the most common Gram-negative organism causing neonatal meningitis. E. coli meningitis usually occurs in newborns or infants under 3 months of age, and develops as the result of hematogenous spread after gastrointestinal colonization and bloodstream invasion of E. coli K1 [1]. During the last decade, several screening technologies have been applied to study the pathogenetic mechanisms of E. coli K1 *Corresponding author: Division of Pediatric Infectious Diseases, Johns Hopkins University School of Medicine, 720 Rutland Ave, Ross 1109, Baltimore, MD 21205, Tel: (410) 614-3917, Fax: (410) 614-1491, e-mail: kwangkim@jhmi.edu.…”

Section: Introductionmentioning

confidence: 99%

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Transcriptome of Escherichia coli K1 bound to human brain microvascular endothelial cells

Xie

Parthasarathy

Cello

et al. 2008

Biochemical and Biophysical Research Communications

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Escherichia coli K1 is the most common Gram-negative organism causing neonatal meningitis. Binding to human brain microvascdular endothelial cells (HBMEC) is an essential step for E. coli K1 traversal of the blood-brain barrier. In this study, we examined expression profiles of E. coli K1 strain RS218 during its binding to HBMEC. Comparison of HBMEC-bound E. coli K1 with collagenbound E. coli revealed more than one hundred genes whose expression patterns were significantly changed in HBMEC-bound E. coli K1, but not in collagen-bound E. coli K1. These genes are involved mainly in cell surface decorations, cellular function, and nitrogen metabolism. The roles of several representative genes including frdA, clpB, carA, and ompT in HBMEC binding were verified with their isogenic mutants, which exhibited significantly less HBMEC binding capability compared to that of the parent strain. This transcriptome analysis provided us with the first genomic-level view of E. coli and HBMEC interactions.

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Section: Introductionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Transcriptome of Escherichia coli K1 bound to human brain microvascular endothelial cells

Xie

Parthasarathy

Cello

et al. 2008

Biochemical and Biophysical Research Communications

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“…The mortality and morbidity associated with neonatal meningitis remain significant in spite of advances in antimicrobial chemotherapy (Kim, 2003). Escherichia coli k1 is a successful pathogen capable of invading the brain despite the protective effect of physiological barriers between the blood stream and the central nervous system.…”

Section: Siderophores -Potential Candidate In the Therapy Of Neonatalmentioning

confidence: 99%

Siderophores – potential candidate in the therapy of neonatal meningitis

Dam

2005

Journal of Medical Microbiology

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“…CNF1 is a cytoplasmic protein and its secretion is, therefore, a strategy utilized by meningitis-causing E. coli K1 to invade the blood-brain barrier (Khan et al, 2002;Kim, 2003Kim, , 2008. However, it remains incompletely understood how CNF1 secretion occurs.…”

Section: Introductionmentioning

confidence: 99%

YgfZ contributes to secretion of cytotoxic necrotizing factor 1 into outer-membrane vesicles in Escherichia coli

Kim

2012

Microbiology

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Cytotoxic necrotizing factor 1 (CNF1), a Rho GTPase-activating bacterial toxin, has been shown to contribute to invasion by meningitis-causing Escherichia coli K1 of human brain microvascular endothelial cells (HBMEC), which constitute the blood-brain barrier. However, CNF1 is a cytosolic protein and it remains unclear how its secretion occurs, contributing to E. coli invasion of HBMEC. To investigate the genetic requirement for CNF1 secretion in E. coli K1 strain RS218, we performed mini-Tn5 in vitro mutagenesis and constructed a transposon mutant library of strain NBC, in which b-lactamase was fused to the C-terminus of CNF1 in the chromosome of strain RS218. We identified a transposon mutant (NBC-1E6) that exhibited reduced b-lactamase activity in its culture supernatant and had the transposon inserted into the ygfZ gene. When ygfZ was deleted from the genome of strain RS218 (DygfZ), the translocation of CNF1 into HBMEC was impaired. Subcellular localization analysis of CNF1 demonstrated that YgfZ, a periplasmic protein, contributes to secretion of CNF1 into outer-membrane vesicles (OMVs). The DygfZ mutant was significantly defective in invasion of HBMEC compared to the parent E. coli K1 strain. The defects of the DygfZ mutant in CNF1 secretion into OMVs and translocation into HBMEC as well as invasion of HBMEC were abrogated by complementation with ygfZ. Taken together, our findings demonstrate that YgfZ contributes to CNF1 secretion into OMVs in meningitis-causing E. coli K1. INTRODUCTIONCNF1, the paradigm of the Rho GTPase-activating bacterial toxins (Boquet, 2001;Knust & Schmidt, 2010;Lemonnier et al., 2007), is frequently associated with uropathogenic and meningitis-causing Escherichia coli strains (Khan et al., 2002;Landraud, et al., 2000). CNF1 activates Rho GTPases by deamidation of glutamine 63, converting it into glutamic acid, thus inhibiting GTPhydrolysing activity, resulting in constitutive activation of Rho GTPase. CNF1 has been shown to contribute to polymerization of F-actin, increased formation of stress fibres and phagocytosis (Caprioli et al., 1983;Falzano et al., 1993;Flatau et al., 1997;Schmidt et al., 1997; VouretCraviari et al., 1999). CNF1-like toxins have also been found in other bacteria, including the dermonecrotic toxin of Bordetella spp. and the CNFc from Yersinia pseudotuberculosis (Knust & Schmidt, 2010;Kume et al., 1986;Lockman et al., 2002).We have shown that CNF1 contributes to invasion by E. coli K1 of human brain microvascular endothelial cells (HBMEC) and penetration into the brain via the interaction with its receptor, 37 laminin receptor precursor (37LRP)/67 laminin receptor (67LR) (Chung et al., 2003;Khan et al., 2002;Kim et al., 2005). CNF1 is a cytoplasmic protein and its secretion is, therefore, a strategy utilized by meningitis-causing E. coli K1 to invade the blood-brain barrier (Khan et al., 2002;Kim, 2003Kim, , 2008. However, it remains incompletely understood how CNF1 secretion occurs. No typical signal peptide is found in the CNF1 sequence. Recent studies have ...

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Pathogenesis of bacterial meningitis: from bacteraemia to neuronal injury

Cited by 366 publications

References 94 publications

Transcriptome of Escherichia coli K1 bound to human brain microvascular endothelial cells

Transcriptome of Escherichia coli K1 bound to human brain microvascular endothelial cells

Siderophores – potential candidate in the therapy of neonatal meningitis

YgfZ contributes to secretion of cytotoxic necrotizing factor 1 into outer-membrane vesicles in Escherichia coli

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