The rare O104:H4 strain responsible for the deadliest Escherichia coli outbreak in history is a clone that combines the virulence potentials of two different pathogens--the Shiga toxin producing ability of enterohemorrhagic E coli (EHEC) and the adherence abilities of enteroaggregative E coli (EAEC)--which might explain its greater virulence and the unusually high number of infections resulting in complications and death. The findings published Online First in The Lancet Infectious Diseases, have profound implications for disease detection, reporting, and food safety.
Most people with EHEC infection recover completely and usually fewer than 10% develop serious complications such as the haemolytic uraemic syndrome (HUS), a potentially fatal form of kidney failure. In Germany, about 1000 symptomatic Shiga-toxin-producing E coli infections and 60 cases of HUS are reported annually. But by June 20 this year, after an outbreak of HUS and bloody diarrhoea caused by E coli strain O104:H4, the numbers were alarmingly high--2684 and 810 respectively.
To better understand the seemingly greater virulence of the outbreak strain, a German team led by Helge Karch from the University of Münster investigated the virulence profiles of the O104:H4 strain by analysing 80 bacteria samples from patients in the outbreak that were recovered between May 23 and June 2, 2011. Samples were tested for the presence of Shiga-toxin-producing E coli virulence genes but also for virulence genes of other intestinal pathogenic E coli. All samples were also tested for underlying characteristics, ability to adhere to cells similar to those that line the gut, and antibiotic susceptibility.
The researchers identified that all isolates were from the HUSEC041 clone (sequence type 678), first isolated from a patient with HUS in Germany in 2001.
Unusually, all isolates produced both the Shiga toxin (Stx2) typical of EHEC and the "stacked-brick" adherence pattern of aggregates characteristic of EAEC (a trait that enables bacteria to gather together and stick to the cells lining the gut).
Additionally, the outbreak isolates had an extended-spectrum ß-lactamase (ESBL) antibiotic resistance profile rendering them resistant to all penicillins and cephalosporins but susceptible to carbapenems.
The authors suggest: "The enhanced adherence of this strain to intestinal epithelial cells might facilitate systemic absorption of Shiga toxin and could explain the high frequency of progression to HUS. Antibiotic resistance might also play a part if ß-lactam drugs used to treat the infection suppressed competing microbiota."
They add: "Although we lack an explanation for increased virulence, this outbreak tragically shows that blended virulence profiles in enteric pathogens introduced into susceptible populations can have serious consequences for infected people."
In a Comment, Hugh Pennington Emeritus Professor of The University of Aberdeen, Aberdeen, UK says: "In this large outbreak in Germany, most cases of the syndrome have been in young and middle-aged adults, particularly women. Two factors probably explain this scenario: the patterns of consumption of the vector and an increased likelihood of developing haemolytic uraemic syndrome because of the high virulence of the clone."
He adds: "Karch and colleagues speculate very reasonably that the blending of enterohaemorrhagic and enteroaggregative virulence traits could explain why so many--about 30% of those infected--in the German outbreak have developed haemolytic uraemic syndrome (a variable combination of renal impairment, thrombocytopaenia, haemolytic anaemia, and CNS and myocardial damage)."
Professor Helge Karch, University of Münster, Münster, Germany. T) +49 251 8355 361 E) firstname.lastname@example.org
Or Stefan Dreising, Press Office, University of Münster, Münster, Germany. T) +49 (0)2 51/ 83 5 74 47 E) email@example.com
Hugh Pennington, University of Aberdeen, Aberdeen, UK. T) +44 (0)1224 645136 E) firstname.lastname@example.org
Notes to Editors: For identification of the outbreak strain the researchers used a rapidly iterative process to exploit polymorphisms in a gene (gnd) that co-transfer with the region encoding the adjacent O104 cluster, as well as fliC, which encodes the flagellar antigen. Moreover, they developed a testing scheme that can rapidly and specifically identify this pathogen.