New Developments in Enferic Bacterial Toxins David A. Bobak and Richard L. Guerrant Division of Geogruphic Medicine Depurtrnents of Medicine and Microbiology University of Virginia School of Medicine Charlottesville, Virginia 22908
I . Overview
11. Cholera-like Enterotoxins (CT, LT-I, LT-11)
Ill. Heat-Stable Enterotoxins (ST, and STh) 1V. Other Potential Eschrrichim coli and Vibrio cholerae Enterotoxins V . Closfridirtrn difficilo Toxins A and B VI. Shiga and Shiga-like Toxins VII. Staphylococcal Enterotoxins VIII. CIosrridiitrn prrjkirrgrns Enterotoxin A IX. Conclusion References
1. Overview Developments since the mid- 1950s showing the secretory effects of culture filtrates of Vibrio cholerae and Escherichia coli and the cytotoxic and neurotoxic effects of ShigeIlu and botulinum toxins have increasingly demonstrated the major roles of many bacterial toxins in disease (De et al., 1956) (Table I). Indeed the bacterial toxins such as cholera toxin, E . coli heat-labile and -stable toxins (LT and ST), and pertussis toxin have taught us much about the basic mechanisms of regulation of adenylate cyclase and guanylate cyclase signaling systems as well as the physiologic importance of cyclic nucleotides in regulating intestinal electrolyte transport. Furthermore, the transmissibility of plasmids or phage encoding the cholera-like and heat-stable enterotoxins (Skerman et ul., 1972; Takeda and Murphy, 1978) and their occasional occurrence in a wide range of organisms, including E . coli, Cunipylobacterjejuni, Salmonella, Yersinia, Aerornonas, Citrobacfer, and Klebsiella, suggest that the capacity to proAdvances in Phurrnocology. Volume 23 Copyright 0 1992 by Academic Press. Inc. All nght5 of reproduction
in
any form reserved
85
86
David A. Bobak and Richard 1. Guerrant
Table I Enteric Microbial Virulence Traits" Toxins Secretory enterotoxins Cholera toxin Escherichiu coli LT-1/11 (also Vibrio paraheniol.ytic~us. Klehsiella, Citrobacter, Salmonella, and Campylobacter) E . coli ST, (ST,, or ST,) (Also Yersinia, non-01 Vibrio cholerue. Vibrio mimicus. Citrohacter freundii) E. coli STb EPEC Clostridium diSJicile toxin A C/ostridium perfringens type A Bascdlus cereus enterotoxins (Enteroinvasive E . coli toxin. EIET)" (Enteroaggregative E. coli toxin. EAST) Cytotoxinslneurotoxins Shiga toxin E. coli SLT l/lI/lIvh/Ilvp C. dijjcile toxin A
Pathogenesisb Binds GM, ADP-ribosylates G,, (5-HT. PGE?)
1
C . perfringens C (beta toxin) Staphvlococc~tsaureus enterotoxins
Activates pG cyclase
---f
CAMP
+ cGMP
!
I . Overview
11. Cholera-like Enterotoxins (CT, LT-I, LT-11)
Ill. Heat-Stable Enterotoxins (ST, and STh) 1V. Other Potential Eschrrichim coli and Vibrio cholerae Enterotoxins V . Closfridirtrn difficilo Toxins A and B VI. Shiga and Shiga-like Toxins VII. Staphylococcal Enterotoxins VIII. CIosrridiitrn prrjkirrgrns Enterotoxin A IX. Conclusion References
1. Overview Developments since the mid- 1950s showing the secretory effects of culture filtrates of Vibrio cholerae and Escherichia coli and the cytotoxic and neurotoxic effects of ShigeIlu and botulinum toxins have increasingly demonstrated the major roles of many bacterial toxins in disease (De et al., 1956) (Table I). Indeed the bacterial toxins such as cholera toxin, E . coli heat-labile and -stable toxins (LT and ST), and pertussis toxin have taught us much about the basic mechanisms of regulation of adenylate cyclase and guanylate cyclase signaling systems as well as the physiologic importance of cyclic nucleotides in regulating intestinal electrolyte transport. Furthermore, the transmissibility of plasmids or phage encoding the cholera-like and heat-stable enterotoxins (Skerman et ul., 1972; Takeda and Murphy, 1978) and their occasional occurrence in a wide range of organisms, including E . coli, Cunipylobacterjejuni, Salmonella, Yersinia, Aerornonas, Citrobacfer, and Klebsiella, suggest that the capacity to proAdvances in Phurrnocology. Volume 23 Copyright 0 1992 by Academic Press. Inc. All nght5 of reproduction
in
any form reserved
85
86
David A. Bobak and Richard 1. Guerrant
Table I Enteric Microbial Virulence Traits" Toxins Secretory enterotoxins Cholera toxin Escherichiu coli LT-1/11 (also Vibrio paraheniol.ytic~us. Klehsiella, Citrobacter, Salmonella, and Campylobacter) E . coli ST, (ST,, or ST,) (Also Yersinia, non-01 Vibrio cholerue. Vibrio mimicus. Citrohacter freundii) E. coli STb EPEC Clostridium diSJicile toxin A C/ostridium perfringens type A Bascdlus cereus enterotoxins (Enteroinvasive E . coli toxin. EIET)" (Enteroaggregative E. coli toxin. EAST) Cytotoxinslneurotoxins Shiga toxin E. coli SLT l/lI/lIvh/Ilvp C. dijjcile toxin A
Pathogenesisb Binds GM, ADP-ribosylates G,, (5-HT. PGE?)
1
C . perfringens C (beta toxin) Staphvlococc~tsaureus enterotoxins
Activates pG cyclase
---f
CAMP
+ cGMP
!
