AB5 toxins.

E A Merritt; W G Hol

doi:10.1016/0959-440x(95)80071-9

Home/Archive/PubMed

PubMed · 7648317

AB5 toxins.

E A Merritt·W G Hol

View original source ↗Export metadata ↓

Abstract

Crystal structures of shiga and pertussis toxins have recently revealed a remarkable degree of structural homology among the members of the AB5 class of bacterial toxins. Other structures have provided a detailed view of the molecular basis of receptor binding specificity of cholera toxin, and of the heat-labile enterotoxin of Escherichia coli. These structures also provide tantalizing, but as yet incomplete, information on the site of ADP-ribosylation in the homologous A-subunits of the Escherichia coli heat-labile toxin, cholera toxin, and pertussis toxin.

Explore related subjects

Bacterial Toxins Binding Sites Crystallography, X-Ray GTP-Binding Proteins Gangliosides Glycoproteins Models, Molecular Protein Conformation Protein Folding Protein Structure, Tertiary Receptors, Cell Surface Journal Article Review

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

E A Merritt, W G Hol. 1995. AB5 toxins.. https://doi.org/10.1016/0959-440x(95)80071-9

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2003

Structure-function analysis of the enteroaggregative Escherichia coli plasmid-encoded toxin autotransporter using scanning linker mutagenesis.

The plasmid-encoded toxin (Pet) from enteroaggregative Escherichia coli is a cytopathic serine protease, which is prototypical of a large family of bacterial autotransporter toxins. To further elucidate the structure-function relationships of this toxin, we employed transposon-based scanning linker mutagenesis. A subset of insertions throughout the Pet mature toxin (passenger) domain reduced secretion to the extracellular space. Many of these mutants were undetectable, but secretion of a subset of mutants with insertions in the N-terminal half of the toxin could be restored to wild type secretion levels if cultured in the presence of 0.1% Triton X-100. Secretion of two mutants with insertions at the extreme C terminus was partially restored when co-expressed with a minimal clone of EspP, a related autotransporter protein. Several well secreted mutants with insertions in the N-terminal third of the molecule reduced protease activity over 20-fold, suggesting that the protease domain is located within this N-terminal region of Pet. We have also identified two insertional mutants in the middle of the passenger domain that were proteolytic but no longer cytopathic; these mutants displayed decreased binding and internalization upon incubation with HEp-2 cells. Our data suggest the existence of separate functional domains mediating Pet proteolysis, secretion, and cell interaction.

Bacterial Toxins↗

PubMed2003

Mechanistic studies of the photocatalytic oxidation of microcystin-LR: an investigation of byproducts of the decomposition process.

Microcystins (cyclic heptapeptides) are produced by a number of freshwater cyanobacteria and cause concern in potable water supplies due to their acute and chronic toxicity. The present study reports the structural characterization of the degradation products of the photocatalytic oxidation of microcystin-LR, so aiding the mechanistic understanding of this process. TiO2 photocatalysis is a promising technology for removal of these toxins from drinking water. However, before it can be adopted in any practical application it is necessary to have a sufficient knowledge of degradation byproducts and their potential toxicity. Liquid chromatography-mass spectrometry analysis demonstrated that the major destruction pathway of microcystin appears to be initiated via three mechanisms: UV irradiation, hydroxyl radical attack, and oxidation. UV irradiation caused geometrical isomerization of microcystin converting the (4E), (6E) of the Adda configuration to (4E), 6(Z) or 4(Z), 6(E). Hydroxyl radical attack on the conjugated diene structure of Adda moiety produced dihyroxylated products. Further oxidation cleaved the hydroxylated 4-5 and/or 6-7 bond of Adda to form aldehyde or ketone peptide residues, which then were oxidized into the corresponding carboxylic acids. Photocatalysis also hydrolyzed the peptide bond on the ring structure of microcystin to form linear structures although this appeared to be a minor pathway.

Bacterial Toxins↗

PubMed2003

Effects of cefotaxime and desacetylcefotaxime upon Clostridium difficile proliferation and toxin production in a triple-stage chemostat model of the human gut.

Clostridium difficile is recognized as an important nosocomial pathogen. C. difficile infection (CDI) is thought to arise as a result of depletion of the normal gut flora by antimicrobial agents. Cefotaxime (CTX) is well-known for its propensity to cause CDI, but the reasons behind its particular predisposition to the disease remain unclear. Previous investigations have so far relied upon the hamster model of CDI or human volunteers. We have used a triple-stage chemostat model of the human gut to investigate the behaviour of C. difficile and components of the normal gut flora, in response to exposure to CTX alone, and in combination with its active metabolite desacetylcefotaxime (dCTX). C. difficile remained in a steady state during non-antibiotic exposed periods, with no detectable cytotoxin. During both antibiotic exposure regimens, proliferation of C. difficile and elevated cytotoxin levels were observed. Cessation of antibiotic instillation produced a reduction in cytotoxin levels and viable counts. Decreases in bacterial counts were observed in response to both antibiotic exposure regimens, notably for bifidobacteria and bacteroides. Numbers of bacteroides were profoundly affected by exposure to the CTX/dCTX combination, and this may indicate a possible role for bacteroides in colonization resistance. We believe that the gut model is a promising method for studying C. difficile pathogenesis in conditions analogous to the in vivo situation.

Bacterial Toxins↗