COMPARATIVE TOXICITY AND VIRULENCE OF ESCHERICHIA-COLI CLONES EXPRESSING VARIANT AND CHIMERIC SHIGA-LIKE TOXIN TYPE-II OPERONS

Citation
Aw. Paton et al., COMPARATIVE TOXICITY AND VIRULENCE OF ESCHERICHIA-COLI CLONES EXPRESSING VARIANT AND CHIMERIC SHIGA-LIKE TOXIN TYPE-II OPERONS, Infection and immunity, 63(7), 1995, pp. 2450-2458
Citations number
28
Categorie Soggetti
Immunology,"Infectious Diseases
Journal title
ISSN journal
00199567
Volume
63
Issue
7
Year of publication
1995
Pages
2450 - 2458
Database
ISI
SICI code
0019-9567(1995)63:7<2450:CTAVOE>2.0.ZU;2-Y
Abstract
Shiga-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, design ated SLT-II/O111, SLT-II/OX3a, SLT-II/OX3b, and SLT-II/O48, were clone d in the same orientation in pBluescript. French pressure cell lysates of E. coli DH5 alpha derivatives carrying these plasmids differed mar kedly in cytotoxicity for Vero cells, with 50% cytotoxic doses ranging from 20 to 328,000/ml. The strains also differed in oral virulence fo r streptomycin-treated mice, as judged by survival rate and/or median survival time, but virulence did not necessarily correlate with in vit ro cytotoxicity. The SLT-II type associated with the lowest oral virul ence was SLT-II/O111. Both the overall survival rate and the median su rvival time of mice challenged with clones producing this toxin were s ignificantly greater than that for mice challenged with a clone produc ing 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-176-->Gly substitution in the mature A sub unit. Clones producing SLT-II/O48 and SLT-II/OX3b had similarly high c ytotoxicities for Vero cells, but the latter was more virulent when fe d to streptomycin-treated mice, as judged by median survival time. Exp eriments with clones carrying chimeric O48/OX3b SLT-II operons indicat ed 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 a mino acids (Met-4-->Thr and Gly-102-->Asp, respectively). These findin gs raise the possibility that naturally occurring SLT-II sequence vari ations may impact directly on the capacity of a given SLT-producing E. coli strain to cause disease.