Structural and functional relationships among the RTX toxin determinants of gram-negative bacteria.
The RTX (repeats in toxin) cytolytic toxins represent a family of important virulence factors that have disseminated widely among Gram-negative bacteria. They are characterised by a series of glycine-rich repeat units at the C-terminal end of each protein. They also have other features in common. Secretion from the cell occurs without a periplasmic intermediate by a novel mechanism which involves recognition of a signal sequence at the C-terminus of the toxin by membrane-associated proteins that export the toxin directly to the outside of the cell. The structural gene for each protein encodes an inactive toxin which is modified post-translationally to an active cytotoxic form by another gene product before secretion. The genes for toxin synthesis, activation and secretion are for the most part grouped together on the chromosome and form an operon. The toxins all create pores in the cell membrane of target cells leading to eventual cell lysis and they appear to require Ca2+ for cytotoxic activity. Although the toxins have a similar mode of action, they vary in target cell specificity. Some are cytotoxic for a wide variety of eukaryotic cell types while others exhibit precise target cell specificity and are only active against leukocytes from certain host species. The characteristic glycine-rich repeat units have been identified in other exoproteins besides those with cytotoxic activity and it is likely that the novel secretory mechanism has been harnessed by a variety of pathogens to release important virulence-associated factors from the cell or to locate them on the cell surface.
Coote
J G
JG
Microbiology Department, University of Glasgow, U.K.
D001427:Bacterial Toxins / Q000737:chemistry* / Q000235:genetics; D003603:Cytotoxins / Q000737:chemistry* / Q000235:genetics; D006090:Gram-Negative Bacteria / Q000737:chemistry* / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D013329:Structure-Activity Relationship; D014774:Virulence
D001427:Bacterial Toxins; D003603:Cytotoxins