The effects of cytotoxic necrotizing factor 1 expression in the uptake of Escherichia coli K1 by macrophages and the onset of meningitis in newborn mice.

Abstract	Macrophages are a permissive niche for E. coli K1 multiplication for which the interaction of the bacterial outer membrane protein A and its cognate receptor CD64 are critical. Using in vitro immunofluorescence and live microscopy with ex vivo macrophage cultures from RFP-Lifeact mice, we show that cytotoxic necrotizing factor 1 (CNF1) secreted by E. coli K1 sequesters cellular actin toward microspike formation, thereby limiting actin availability for OmpA-mediated bacterial invasion. Surprisingly, the observed effects of CNF1 occur despite the absence of 67-kDa laminin receptor in macrophages. Concomitantly, the CNF1 deletion mutant of E. coli K1 (Δcnf1) invades macrophages and the brains of newborn mice in greater numbers compared to wild-type. However, the Δcnf1 strain induces less severe pathology in the brain. These results suggest a novel role for CNF1 in limiting E. coli K1 entry into macrophages while exacerbating disease severity in the brains of newborn mice.
Authors	Alexander C Chang, Subramanian Krishnan, Nemani V Prasadarao
Journal	Virulence (Virulence) Vol. 7 Issue 7 Pg. 806-18 (10 02 2016) ISSN: 2150-5608 [Electronic] United States
PMID	27221788 (Publication Type: Journal Article)
Chemical References	Actins Bacterial Outer Membrane Proteins Bacterial Toxins Escherichia coli Proteins Receptors, IgG cytotoxic necrotizing factor type 1 OMPA outer membrane proteins
Topics	Actins Animals Animals, Newborn Bacterial Outer Membrane Proteins (metabolism) Bacterial Toxins (genetics, immunology, metabolism) Brain (microbiology, pathology) Cells, Cultured Disease Progression Escherichia coli (genetics, physiology) Escherichia coli Proteins (genetics, immunology, metabolism) Fluorescent Antibody Technique Humans Macrophages (immunology, microbiology) Meningitis, Escherichia coli (immunology, microbiology) Mice Receptors, IgG (metabolism) Sequence Deletion

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