Cravioto, Alejandro

Bioline International

J HEALTH POPUL NUTR    2005 Dec;23(4):303-304 © 2005 ICDDR,B: Centre for Health and Population ResearchISSN 1606-0997        $ 5.00+0.20EDITORIALImportance of Escherichia coli Strains Producing VerotoxinsCorrespondence and reprint requests should be addressed to:Prof. Alejandro Cravioto, Deputy Executive DirectorICDDR,B: Centre for Health and Population ResearchGPO Box 128, Dhaka 1000 (Mohakhali, Dhaka 1212)BangladeshEmail: acravioto@icddrb.orgThe production of a heat-labile protein unrelated tocholera toxin was described in the 1960s in studies ofEscherichia coli isolated from animals (1,2). However,it was not until 1982 when Riley et al. reported an out-break of haemorrhagic colitis associated with an E. colithat produced the same heat-labile toxin, and that thesestrains were considered hazardous to humans (3). Asecond interesting outcome of the study by Riley et al.was that E. coli strains isolated during this outbreak be-longed to a serotype that had not been previously asso-ciated with human disease. Over the subsequent years,this 'new' serotype, O157:H7, became the predominantcausal pathogen worldwide for both haemorrhagic colitisand haemolytic-uraemic syndrome. Outbreaks of haemor-rhagic colitis and haemolytic-uraemic syndrome asso-ciated with O157:H7 E. coli strains have been reportedin Canada, the United States, Europe, and Japan (4).  The production of heat-labile cytotoxin is not res-tricted to E. coli O157:H7, with studies showing thatother E. coli strains have this character (5), and the com-mon trait among these bacteria is the ability to produceheat-labile cytotoxin. Such strains have been groupedaccording to specific characteristics: Verocytotoxin-pro-ducing E. coli, which relates to the capacity to destroymonolayers of vero cells in culture; enterohaemorrhag-ic E. coli for their capacity to cause haemorrhagic coli-tis and haemolytic-uraemic syndrome; and more recently,Shiga-toxin (Stx)-producing E. coli (STEC) for the si-milarity of the toxin produced by these E. coli strainswith that produced by Shigella dysenteriae type 1 (4).Given the severity of the diseases associated withinfection by these strains and their importance as theleading cause of acute renal failure in children aged lessthan five years in developed countries, an internationalnetwork of interested laboratories has been establishedto conduct surveillance and determine the burden ofdisease associated with these infections. Concerned labo-ratories in less-developed areas of the world have alsojoined this international endeavour to determine the im-portance of such strains as part of the spectrum of diar-rhoeal diseases in their own environments.Studies conducted in less-developed areas of the worldhave already shown little participation of STEC strainsas causal agents of diarrhoeal disease in these countries(4). What is interesting is that the conditions for trans-mission of these strains from animals to humans exist,as do the inherent problems relating to basic sanitationand safe drinking-water. Therefore, the question that re-mains to be answered is why there has been such a lackof isolation of STEC in these areas.  The reason is not due to a lack of technical capacity inparticipating laboratories or to inadequate surveillancesystems in these areas. Active surveillance at the commu-nity level has been conducted in several longitudinal sur-veys of diarrhoeal disease in less-developed countries inwhich other types of pathogenic strains of E. coli havebeen properly identified and characterized by state-of-the-art methods (4). Therefore, there has to be another expla-nation for the lack of participation of STEC as a causeof major outbreaks of disease in these areas of the world.In this issue of JHPN, Voravuthikunchai et al. reportthe results of a study conducted in Thailand to deter-mine whether the presence of a humoral immune res-ponse to O157 lipopolysaccharide (LPS) could be a rea-son for the lack of disease associated with infection bythese strains in people with diarrhoea in that country(6). An IgM response to the O157 LPS was found bythese authors in 12% of 332 serum samples obtainedfrom healthy blood donors and patients with diseasesunrelated to diarrhoea. In the case of an IgG response,23% of these same samples showed a positive responseto O157 LPS. The authors conclude that possible expo-sure to cross-reacting antigens in these subjects couldbe the reason for finding this response in their sera, anda possible protection against colonization and diseaseassociated with O157:H7 strains.Similar findings have been reported in previous stu-dies conducted in serum samples obtained from humansCravioto AJ Health Popul Nutr Dec 2005304in other less-developed areas of the world. Navarro et al.(7) showed that serum samples obtained from Mexicanadults and children aged less than one year not only res-ponded to the O157 LPS, but also to two other cross-reacting LPSs: O7 and O116. They concluded that colo-nization by any of these strains could have a protectiveimmune response against infection by O157 strains,which could explain why strains belonging to this sero-type are seldom isolated from the Mexican population,especially when a similar immune response to these LPSswas also found in breastmilk samples obtained by theauthors. In the same study (7), Navarro et al. reported thatrabbit antiserum raised against O6, O114, and O157 LPSshas a homologous and a heterologous bactericidal capa-city against strains with these LPSs, and that serumsamples obtained from herds of cattle in different partsof Mexico showed a similar response to that found inhumans, which explains why the local animals are sel-dom shown to be colonized by O157:H7 strains (8,9).  The presence of anti-LPS antibodies in serum couldalso reflect the presence of a similar response in the in-testine. In this case, the presence of specific IgA anti-bodies against cross-reacting non-O157 bacterial anti-gens could inhibit the pathogenic capacity of O157:H7strains through the temporal loss of critical virulencefactors used by these strains to cause disease in humans,as shown recently by Mellmann et al. (10).   The lack of isolation of O157:H7 strains in less-deve-loped areas of the world does not mean, however, thatSTEC strains are not part of the burden of diarrhoeal dis-ease in children from these areas. E. coli belonging to sero-types other than O157:H7 have been associated with bothoutbreaks and sporadic diseases in animals and humans(5,11). Given these findings, it seems necessary to de-termine the epidemiological importance of all E. colistrains producing verocytotoxin isolated in these areas,regardless of their serotype, to determine the real partici-pation of these pathogens in the burden of diarrhoealdisease in humans living in different parts of the world.  REFERENCES1. Smith HW, Halls S. Studies on Escherichia colienterotoxin. J Pathol Bacteriol 1967;93:531-43.2. Smith HW, Halls S. The transmissible nature of thegenetic factor in Escherichia coli that controls entero-toxin production. J Gen Microbiol 1968;52:319-4l.3. Riley LW, Remis RS, Helgerson SD, McGee HB,Wells JG, Davis BR et al. Hemorrhagic colitis asso-ciated with a rare Escherichia coli serotype. N EnglJ Med 1983;308:681-5.  4. Tarr PI, Gordon CA, Chandler WL. Shiga-toxin-pro-ducing Escherichia coli and haemolytic uraemicsyndrome. Lancet 2005;365:1073-86.5. Scheutz F, Beutin L, Smith HR. Characterization ofnon-O157 verotoxigenic E. coli (VTEC) isolatedfrom patients with haemolytic uraemic syndrome(HUS) world-wide from 1982-2000 [abstract 203].In: Abstracts from the 4th International Symposiumand Workshop on Shiga toxin (Verocytotoxin)-Pro-ducing Escherichia coli Infections, Kyoto, 2000.Kyoto: VTEC 2000 Organizing Committee, 2000. 6. Voravuthikunchai SP, Chaowana C, Perepat P, IidaT, Honda T. Antibodies among healthy populationof developing countries against enterohaemorrhagicEscherichia coli O157:H7. J Health Popul Nutr 2005;23:305-10. 7. Navarro A, Eslava C, Hernandez U, Navarro-HenzeJL, Aviles M, Garcia-de la Torre G et al. Antibodyresponses to Escherichia coli O157 and other lipo-polysaccharides in healthy children and adults. ClinDiagn Lab Immunol 2003;10:797-801.8. Navarro A, Eslava C, Licona D, León LA, Pérez G,Hernández JM et al. Serologic evidence of a hete-rologous response against Escherichia coli O157LPS in cattle from different farms in Mexico(abstract D-140). In: Abstracts, 104th GeneralMeeting, American Society for Microbiology, NewOrleans, LA, May, 2004. 9. Navarro A, Gutiérrez A, Trejo A, Licona D, León L,Hernández JM et al. The low isolation frequencyof Escherichia coli O157 in Mexican cattle is asso-ciated with a heterologous immune response to crossreacting LPS antigens (abstract D-186). In:Abstracts, 105th General Meeting, American Societyfor Microbiology, New Orleans, LA, May, 2005.10. Mellmann A, Bielaszewska M, Zimmerhackl LB,Prager R, Harmsen D, Tschäpe et al. Enterohemor-rhagic Escherichia coli in human infection: in vivoevolution of a bacterial pathogen. Clin Infect Dis2005;41:785-92.11. Brooks JT, Sowers EG, Wells JG, Greene KD, GriffinPM, Hoekstra RM et al. Non-O157 Shiga-toxin-producing Escherichia coli infections in the UnitedStates, 1983-2002. J Infect Dis 2005;192:1422-9.Alejandro CraviotoICDDR,B: Centre for Health and Population ResearchGPO Box 128, Dhaka 1000 (Mohakhali, Dhaka 1212)BangladeshEmail: acravioto@icddrb.org

Importance of Escherichia Coli Strains Producing Verotoxins

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