Targeting E. coli invasion of the blood-brain barrier for investigating the pathogenesis and therapeutic development of E. coli meningitis.
Cell Microbiol
; 22(10): e13231, 2020 10.
Article
in En
| MEDLINE
| ID: mdl-32447809
ABSTRACT
Escherichia coli is the most common Gram-negative bacillary organism causing neonatal meningitis. Escherichia coli meningitis remains an important cause of mortality and morbidity, but the pathogenesis of E. coli penetration of the blood-brain barrier remains incompletely understood. Escherichia coli entry into the brain occurs in the meningeal and cortex capillaries, not in the choroid plexus, and exploits epidermal growth factor receptor (EGFR) and cysteinyl leukotrienes (CysLTs) for invasion of the blood-brain barrier. The present study examined whether EGFR and CysLTs are inter-related in their contribution to E. coli invasion of the blood-brain barrier and whether counteracting EGFR and CysLTs is a beneficial adjunct to antibiotic therapy of E. coli meningitis. We showed that (a) meningitis isolates of E. coli exploit EGFR and CysLTs for invasion of the blood-brain barrier, (b) the contribution of EGFR is upstream of that of CysLTs, and (c) counteracting EGFR and CysLTs as an adjunctive therapy improved the outcome (survival, neuronal injury and memory impairment) of animals with E. coli meningitis. These findings suggest that investigation of host factors contributing to E. coli invasion of the blood-brain barrier will help in enhancing the pathogenesis and development of new therapeutic targets for E. coli meningitis in the era of increasing resistance to conventional antibiotics.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Quinolines
/
Sulfides
/
Blood-Brain Barrier
/
Leukotrienes
/
Meningitis, Escherichia coli
/
Cyclopropanes
/
Cysteine
/
Escherichia coli
/
ErbB Receptors
/
Gefitinib
Type of study:
Etiology_studies
Limits:
Animals
/
Female
/
Humans
/
Male
/
Newborn
Language:
En
Journal:
Cell Microbiol
Journal subject:
MICROBIOLOGIA
Year:
2020
Document type:
Article
Affiliation country:
United States
Publication country:
IN
/
INDIA
/
ÍNDIA