[Mechanism of cell damage by E. coli hemolysin].
Many strains of E. coli elaborate a hemolysin which is responsible for the zone of beta-hemolysis surrounding bacterial colonies on blood agar. The significance of this cytolysin as a determinant of bacterial pathogenicity has been established in animal models with the use of genetically engineered, isogenic bacterial strains. An analogous role in human infections has been inferred from the high association of hemolysin production with disease. Studies at a molecular genetical level have defined 4 genes that are required for the synthesis, post-translational modification and secretion of the hemolysin. The structural gene hlyA encodes for a 107-110,000 polypeptide which must be modified in an unknown manner to its active form by the product of the neighboring hlyC gene. Genes hlyB and hlyD encode for proteins that export the molecule to the extracellular medium. The signal for secretion is contained in the C-terminal portion of the toxin molecule. The secreted hemolysin attacks plasma membranes of target mammalian cells by inserting as a monomer into the bilayer and generating a hydrophilic transmembrane pore of approximately 2 nm effective diameter. The pore displays a marked selectivity for cations over anions and pore-opening is dependent on the presence of a correct transmembrane potential. Binding to a membrane target does not require the presence of a specific receptor, and pores may be generated in planar lipid membranes consisting solely of phosphatidylcholine. Pore formation in nucleated cells can trigger secondary reactions such as stimulation of arachidonate metabolism with release of lipid mediators, probably initiated by passive influx of extracellular Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS)
Bhakdi
S
S
Institut für Medizinische Mikrobiologie, Giessen.
Mackman
N
N
Menestrina
G
G
Hugo
F
F
Seeger
W
W
Holland
I B
IB
D000818:Animals; D002477:Cells / Q000187:drug effects*; D004926:Escherichia coli / Q000235:genetics* / Q000472:pathogenicity; D005796:Genes; D005798:Genes, Bacterial; D006460:Hemolysin Proteins / Q000235:genetics / Q000494:pharmacology*; D006801:Humans
D006460:Hemolysin Proteins
Mechanismus der Zellschädigung durch E. coli-Hämolysin.