National Reference Laboratory for Escherichia coli, Federal Institute for Risk Assessment, Berlin, Germany
, Causes and Eﬀects of the Rise of aHuman Pathogen
Address of author: National Reference Laboratory for Escherichia coli (NRL-E.coli), Federal Institute for Risk Assessment(BfR), Diedersdorfer Weg 1, D-12277 Berlin, Germany; Tel.: +49 30 8412 2259; fax: +49 30 8412 2983;E-mail: firstname.lastname@example.orgReceived for publication November 10, 2004
Shiga toxin (Stx) [Verotoxin (VT)]-producing
(STEC), also called enterohaemorrhagic
or VTEC areemergingzoonoticagentsandbecamemostimportantashumanpathogens, particularly in the industrialized countries. Produc-tion of cytotoxins, also called Stx or VT, is the major patho-genicity determinant of STEC, which can cause life-threateninghaemorrhagic diseases in humans. The spectrum of STECphenotypes is diverse and domestic and wildlife animals con-stitute important reservoirs for these bacteria. STECare spreadfrom animal faeces to the environment, water and food. Inges-tionofcontaminatedfoodstuﬀandwater,aswellascontactwiththe environment, STEC-excreting animals or humans are themajor sources of human infection. Economical changes in ani-malandfoodproduction,alterationofconsumerhabitsandlackof speciﬁc immune response, particularly in urbanized popula-tions, have contributed to the recent spread of STEC as a zoo-notic agent. Supranational surveillance networks as well asnational reference laboratories as sentinels play an importantroleinthepreventionandcontrolofSTECinfectionsinhumans.Developmentofnewvaccinesandprobioticsmayserveasfuturetools to control the spread of STEC in animals and humans.
Among the pathogenic
(EHEC) became most important ashuman pathogens, particularly in the industrialized countrieswith moderate climate. The rapid increase of human EHECinfections reported in the last decades has alarmed publichealth authorities and has raised a debate on the microbiolo-gical safety of food of animal origin, which is often incrim-inated as source of EHEC transmission to humans. Thereasons for the recent emergence and rapid spread of EHECinfections in diﬀerent parts of the world were investigated fordiﬀerent aspects and are far from being fully recognized.Current data indicate that manifold factors contribute to thechange in emergence of these bacterial pathogens and the aimof this review is to present some of the most important criteriawhich could have contributed to the spread of these pathogens.
were deﬁned as a subgroup of Shiga toxin (Stx)-producing
(STEC) which wereknown to cause haemorrhagic colitis (HC) and haemolyticuraemic syndrome (HUS) in humans (Levine, 1987). TheEHEC prototype strain,
O157:H7, became ﬁrstknown as a human pathogen in 1982 as causative agent infoodborne-outbreaks associated with consumption of undercooked beef (Riley et al., 1983). EHEC were deﬁnedas STEC showing similar clinical, epidemiological andpathogenic features as the EHEC prototype strain,
O157:H7 (Levine, 1987). Later, the term EHEC was used forthose STEC which have been demonstrated to causediarrhoea in humans (Anonymous, 1997) and it wasproposed to divide EHEC into
according to the presence of other virulence attributes suchas the
gene for bacterial intimate adherence and theplasmid located E-
gene encoding production of enterohaemolysin (Nataro and Kaper, 1998). The divisionof Stx-producing strains into STEC and EHEC is notvery clear-cut, because it is not proved if any of thenaturally occurring STEC strains are apathogenic forhumans. To avoid confusion in nomenclature, the termSTEC will be used for all types of Stx-producing
inthis review.On the other hand, it is certain that STEC strains showconsiderable diﬀerences regarding their virulence and patho-genicity. The absence of virulence markers such as the
-gene does not necessarily indicate that these strains possess alower virulence for humans (Paton et al., 1999). Apart fromSTEC O157:H7, certain other STEC types which representclonal groups, such as motile and non-motile strains of O26:[H11], O103:H2, O111:[H8] and O145:[H28] were associ-ated with increased virulence for humans and were morefrequently associated with HC and HUS than other STECtypes. Besides this well known
gang of ﬁve
, other emerginghighly virulent STEC types such as O118:[H16] andO121:[H19] were identiﬁed more recently (Maidhof et al.,2002; Tarr et al., 2002). The continuous evolution of thesepathogens is triggered by selective pressure from the hostimmune system and from the environment. It was demonstra-ted that STEC undergo frequent genetic rearrangements intheir chromosome, their virulence plasmids,
-phages and inthe LEE pathogenicity islands coding for the attaching andeﬀacing (A/E) phenotype (Brunder et al., 1999; Beutin et al.,2005; Garrido et al., 2006). The future emergence of newgenetic variants of highly virulent STEC clones is thereforevery likely.
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J. Vet. Med. B
2006 The AuthorJournal compilation
2006 Blackwell Verlag, BerlinISSN 0931–1793