title: 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.affiliation: a Division of Infectious Diseases and Department of Pediatrics , Children's Hospital Los Angeles , Los Angeles , CA , USA.
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Chang
authors.affiliation: a Division of Infectious Diseases and Department of Pediatrics , Children's Hospital Los Angeles , Los Angeles , CA , USA.
authors.forename: Subramanian
authors.initials: S
authors.lastname: Krishnan
authors.affiliation: a Division of Infectious Diseases and Department of Pediatrics , Children's Hospital Los Angeles , Los Angeles , CA , USA.|b Department of Surgery , Children's Hospital Los Angeles , Los Angeles , CA , USA.|c Keck School of Medicine , University of Southern California , Los Angeles , CA , USA.
authors.forename: Nemani V
authors.initials: NV
authors.lastname: Prasadarao
mesh_terms: D000199:Actins; D000818:Animals; D000831:Animals, Newborn; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D001427:Bacterial Toxins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D001921:Brain / Q000382:microbiology / Q000473:pathology; D002478:Cells, Cultured; D018450:Disease Progression; D004926:Escherichia coli / Q000235:genetics / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000382:microbiology*; D020814:Meningitis, Escherichia coli / Q000276:immunology / Q000382:microbiology*; D051379:Mice; D017452:Receptors, IgG / Q000378:metabolism; D017384:Sequence Deletion
chemical_list: D000199:Actins; D001425:Bacterial Outer Membrane Proteins; D001427:Bacterial Toxins; D029968:Escherichia coli Proteins; D017452:Receptors, IgG; C060296:cytotoxic necrotizing factor type 1; C078167:OMPA outer membrane proteins
keywords: CNF1; E. coli K1; invasion; macrophages; meningitis