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The 2011 Shiga toxin-producing Escherichia coli O104:H4 German outbreak: a lesson in genomic plasticity

2011; Elsevier BV; Volume: 17; Issue: 8 Linguagem: Inglês

10.1111/j.1469-0691.2011.03620.x

1469-0691

Érick Denamur,

Enterobacteriaceae and Cronobacter Research

Escherichia coli is known as a versatile bacterial species encompassing both commensal and intraintestinal and extraintestinal pathogenic strains. An E. coli genome contains between 4200 and 5500 genes, with <2000 genes being conserved among all strains of the species (the core genome). Also, the pan-genome (i.e. all of the non-orthologous genes found in the species) consists of almost 20 000 genes [1Touchon M Hoede C Tenaillon O et al.Organised genome dynamics in theEscherichia coli species results in highly diverse adaptive paths.PLoS Genet. 2009; 5: e1000344Crossref PubMed Scopus (809) Google Scholar]. Continuous gene flux has occurred during E. coli divergence, as a result of horizontal gene transfers and deletions confined to a small number of conserved positions in the chromosome. This chromosomal plasticity accelerates the adaptation of E. coli to varied environments and lifestyles, as it allows multiple gene combinations that, with epistatic interactions, result in phenotypic diversification. The outbreak of bloody diarrhoea and haemolytic–uraemic syndrome in Germany in May and June 2011, caused by an E. coli O104:H4 strain [2Frank C Faber M Askar M et al.Large and ongoing outbreak of haemolytic uraemic syndrome, Germany, May 2011.Euro Surveill. 2011; 16 (pii: 19878)Google Scholar], dramatically illustrates this tremendous E. coli genome plasticity. Owing to the advances in high-throughput sequencing technologies, several complete sequences of isolates from the outbreak were determined within a few days in China and in Germany [3Kupferschmidt K Germany. Scientists rush to study genome of lethalE. coli.Science. 2011; 332: 1249-1250Crossref PubMed Scopus (14) Google Scholar]. It appears that the strain, which belongs to the B1 phylogenetic group of E. coli [4Tenaillon O Skurnik D Picard B Denamur E The population genetics of commensalEscherichia coli.Nat Rev Microbiol. 2010; 8: 207-217Crossref PubMed Scopus (818) Google Scholar], is of multilocus sequence type (ST)678 (http://mlst.ucc.ie) and exhibits an O104:H4 serotype [5Scheutz F Moller Nielsen E Frimodt‐Moller J Characteristics of the enteroaggregative Shiga toxin/verotoxin‐producingEscherichia coli O104:H4 strain causing the outbreak of haemolytic uraemic syndrome in Germany, May to June 2011.Euro Surveill. 2011; 16 (pii:19889)PubMed Google Scholar]. It shares 93% of its sequence with another O104:H4 ST678 strain, E. coli 55989, that was isolated in the 1990s in Bangui (Central African Republic) from a human immunodeficiency virusinfected adult with chronic diarrhoea [1Touchon M Hoede C Tenaillon O et al.Organised genome dynamics in theEscherichia coli species results in highly diverse adaptive paths.PLoS Genet. 2009; 5: e1000344Crossref PubMed Scopus (809) Google Scholar, 6Mossoro C Glaziou P Yassibanda S et al.Chronic diarrhea, hemorrhagic colitis, and hemolytic–uremic syndrome associated with HEp‐2 adherentEscherichia coli in adults infected with human immunodeficiency virus in Bangui, Central African Republic.J Clin Microbiol. 2002; 40: 3086-3088Crossref PubMed Scopus (54) Google Scholar]. Surprisingly, this 55989 strain is an enteroaggregative E. coli (EAEC) strain, with genes encoding proteins involved in the biogenesis of aggregative adherence fimbriae, which mediate the adherence of EAEC to the intestinal mucosa [7Croxen MA Finlay BB Molecular mechanisms ofEscherichia coli pathogenicity.Nat Rev Microbiol. 2010; 8: 26-38Crossref PubMed Scopus (709) Google Scholar]. The German outbreak strain, which can be considered as an enterohaemorrhagic E. coli (EHEC) strain according to the disease that it causes, has acquired, since its divergence from the 55989 strain, the phage-mediated Stx2 Shiga toxin but not the locus of enterocyte effacement located on a 35-kb pathogenic island usually present in EHEC, allowing the attaching bacteria to efface the microvilli. It also possesses, like the 55989 strain, several characteristics of extraintestinal pathogenic E. coli (ExPEC) (https://www.genoscope.cns.fr/agc/microscope/home/index.php) [8Clermont O Olier M Hoede C et al.Animal and human pathogenicEscherichia coli strains share common genetic backgrounds.Infect Genet Evol. 2011; 11: 654-662Crossref PubMed Scopus (152) Google Scholar]. It has the high-pathogenicity island, involved in iron capture, that has been shown to spread within the species by horizontal gene transfer, implicating homologous recombination [9Schubert S Darlu P Clermont O et al.Role of intraspecies recombination in the spread of pathogenicity islands within theEscherichia coli species.PLoS Pathog. 2009; 5: e1000257Crossref PubMed Scopus (77) Google Scholar], and the adhesin-coding gene iha in close vicinity to the siderophore-encoding gene aer, both of which present in the virulent emerging clone O25b ST131 [10Clermont O Lavollay M Vimont S et al.The CTX‐M‐15‐producingEscherichia coli diffusing clone belongs to a highly virulent B2 phylogenetic subgroup.J Antimicrob Chemother. 2008; 61: 1024-1028Crossref PubMed Scopus (240) Google Scholar]. In this regard, the 55989 strain is virulent in a mouse model of septicaemia, as it killed ten mice of ten inoculated [1Touchon M Hoede C Tenaillon O et al.Organised genome dynamics in theEscherichia coli species results in highly diverse adaptive paths.PLoS Genet. 2009; 5: e1000344Crossref PubMed Scopus (809) Google Scholar]. In addition, the German outbreak strain has acquired resistance to numerous antibiotics, including third-generation cephalosporins, owing to several plasmid-borne genes, such as the extended spectrum β-lactamase CTX-M gene [2Frank C Faber M Askar M et al.Large and ongoing outbreak of haemolytic uraemic syndrome, Germany, May 2011.Euro Surveill. 2011; 16 (pii: 19878)Google Scholar], which has been spreading dramatically in E. coli across the world in the last 10 years [11Canton R Coque TM The CTX‐M beta‐lactamase pandemic.Curr Opin Microbiol. 2006; 9: 466-475Crossref PubMed Scopus (894) Google Scholar]. Fortunately, antibiotics are not indicated for treatment of the human disease, as they release the toxin, worsening the symptoms. In sum, it appears that the outbreak strain is an illustration of the genomic plasticity of E coli, with the acquisition of genes providing from different E coli pathovars (EAEC, EHEC, and ExPEC) and the acquisition of antibiotic resistance. But what is the origin of this strain? Stx2-positive EAEC strains were previously described in Bangui during the same study that allowed isolation of the 55989 strain, although other characteristics of these strains, such as the serotype and ST, were not provided [6Mossoro C Glaziou P Yassibanda S et al.Chronic diarrhea, hemorrhagic colitis, and hemolytic–uremic syndrome associated with HEp‐2 adherentEscherichia coli in adults infected with human immunodeficiency virus in Bangui, Central African Republic.J Clin Microbiol. 2002; 40: 3086-3088Crossref PubMed Scopus (54) Google Scholar]. Sporadic cases of Stx2 O104:H4 ST678 strains causing diarrhoea and haemolytic–uraemic syndrome were reported in 2001 in Germany [12Mellmann A Bielaszewska M Kock R et al.Analysis of collection of hemolytic uremic syndrome‐associated enterohemorrhagic Escherichia coli.Emerg Infect Dis. 2008; 14: 1287-1290Crossref PubMed Scopus (227) Google Scholar], in 2004 in France, in 2005 in South Korea [13Bae WK Lee YK Cho MS et al.A case of hemolytic uremic syndrome caused byEscherichia coli O104:H4.Yonsei Med J. 2006; 47: 437-439Crossref PubMed Scopus (68) Google Scholar], in 2009 in Georgia, and in 2010 in Finland [5Scheutz F Moller Nielsen E Frimodt‐Moller J Characteristics of the enteroaggregative Shiga toxin/verotoxin‐producingEscherichia coli O104:H4 strain causing the outbreak of haemolytic uraemic syndrome in Germany, May to June 2011.Euro Surveill. 2011; 16 (pii:19889)PubMed Google Scholar]. Unlike classic EHEC, which has cattle as its reservoir, EAEC seems to have humans as its reservoir. An organic sprout farm near Hamburg has been incriminated [14Struelens MJ Palm D Takkinen J Enteroaggregative, Shiga toxin‐producingEscherichia coli O104:H4 outbreak: new microbiological findings boost coordinated investigations by European public health laboratories.Euro Surveill. 2011; 16 (pii: 19890)PubMed Google Scholar] in the actual outbreak, but the exact mechanism of contamination needs to be determined. The main lesson from this outbreak is that we should be aware of the capacity of the E. coli species to produce new combinations of genes, leading to the emergence of highly aggressive strains. Furthermore, antibiotic pressure in human and veterinary medicine should be kept as low as possible, as it will select for such strains once they become resistant. The author is grateful to O. Clermont and B. Picard for discussion on this manuscript. The author declares that he has no conflict of interest.