Comparative toxicity and virulence of Escherichia coli clones expressing variant and chimeric Shiga-like toxin type II operons

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dc.contributor.authorPaton, A.
dc.contributor.authorBourne, A.
dc.contributor.authorManning, P.
dc.contributor.authorPaton, J.
dc.date.issued1995
dc.description.abstractShiga-like toxin (SLT)-producing strains of Escherichia coli are known to cause diarrhea, hemorrhagic colitis, and hemolytic-uremic syndrome in humans. The SLTs, particularly those related to type II (SLT-II), are a diverse family of toxins which may have differing in vitro or in vivo properties. To examine the impact of naturally occurring SLT-II sequence variation on the capacity of a given E. coli strain to cause disease, operons encoding four different SLT-II-related toxins, designated SLT-II/O111, SLT-II/OX3a, SLT-II/OX3b, and SLTII/ O48, were cloned in the same orientation in pBluescript. French pressure cell lysates of E. coli DH5a derivatives carrying these plasmids differed markedly in cytotoxicity for Vero cells, with 50% cytotoxic doses ranging from 20 to 328,000/ml. The strains also differed in oral virulence for streptomycin-treated mice, as judged by survival rate and/or median survival time, but virulence did not necessarily correlate with in vitro cytotoxicity. The SLT-II type associated with the lowest oral virulence was SLT-II/O111. Both the overall survival rate and the median survival time of mice challenged with clones producing this toxin were significantly greater than that for mice challenged with a clone producing the closely related SLT-II/OX3a. Experiments with clones carrying chimeric O111/OX3a SLT-II operons indicated that the reduced virulence was associated with an Arg-1763Gly substitution in the mature A subunit. Clones producing SLT-II/O48 and SLT-II/OX3b had similarly high cytotoxicities for Vero cells, but the latter was more virulent when fed to streptomycin-treated mice, as judged by median survival time. Experiments with clones carrying chimeric O48/OX3b SLT-II operons indicated that the increased virulence was a function of the A subunit of SLT-II/ OX3b, which differs from the A subunit of SLT-II/O48 by only two amino acids (Met-43Thr and Gly-1023Asp, respectively). These findings raise the possibility that naturally occurring SLT-II sequence variations may impact directly on the capacity of a given SLT-producing E. coli strain to cause disease.
dc.identifier.citationInfection and Immunity, 1995; 63(7):2450-2458
dc.identifier.doi10.1128/iai.63.7.2450-2458.1995
dc.identifier.issn0019-9567
dc.identifier.issn1098-5522
dc.identifier.orcidPaton, J. [0000-0001-9807-5278]
dc.identifier.urihttp://hdl.handle.net/2440/11582
dc.language.isoen
dc.publisherAmerican Society for Microbiology
dc.rights© 1995, American Society for Microbiology
dc.source.urihttp://iai.asm.org/content/63/7/2450
dc.subjectKidney
dc.subjectHela Cells
dc.subjectVero Cells
dc.subjectAnimals
dc.subjectMice, Inbred BALB C
dc.subjectHumans
dc.subjectMice
dc.subjectEscherichia coli
dc.subjectRecombinant Fusion Proteins
dc.subjectOligonucleotide Probes
dc.subjectBacterial Toxins
dc.subjectEnterotoxins
dc.subjectMutagenesis, Site-Directed
dc.subjectSequence Alignment
dc.subjectAmino Acid Sequence
dc.subjectBase Sequence
dc.subjectSequence Homology, Amino Acid
dc.subjectStructure-Activity Relationship
dc.subjectGenes, Bacterial
dc.subjectOperon
dc.subjectMolecular Sequence Data
dc.subjectMale
dc.subjectShiga Toxin 2
dc.subjectChlorocebus aethiops
dc.titleComparative toxicity and virulence of Escherichia coli clones expressing variant and chimeric Shiga-like toxin type II operons
dc.typeJournal article
pubs.publication-statusPublished

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