Genetically related ETEC have spread globally and over time
Enterotoxigenic Escherichia coli (ETEC) bacteria are a major cause of diarrhoea in children below five years of age in low and middle-income countries and also in travellers. An international research effort, which included Karolinska Institutet, has now for the first time analysed the genetic composition of ETEC on a global level. The study is being published in the journal Nature Genetics, and shows that several distinct and stable lineages of ETEC with specific virulence determinants have spread worldwide.
ETEC is estimated to cause diarrhoea in at least 400 million people and cause up to 400,000 deaths each year. This large-scale whole-genome sequencing project, which was led from Sahlgrenska Academy in Gothenburg, shows that ETEC isolates that were collected in Asia, Africa and the Americas during the last 30 years constitute distinct genetically closely related lineages that share specific toxin profiles, O antigens and colonization factors. The research team could show that several major ETEC lineages with specific virulence profiles have emerged between 51 to 174 years ago. The close genetic relationship within the lineages indicates that the virulence genes were acquired once in one bacterium and then spread globally.
Although ETEC is a highly diverse pathogen and previously thought to randomly acquire virulence genes, these findings suggest a specific link between the chromosomal background and plasmids encoding such genes. This changes the perception of how new ETEC strains arise. The results of the study also support that the same ETEC lineages may infect children and adults, as well as travellers in widely different geographic areas.
Develop a vaccine
Since ETEC with the same virulence factor profiles are related and globally present this study supports the strategy taken to develop a vaccine expressing the most prevalent colonization factors in combination with a toxin antigen. The results may also allow identification of additional prevalent vaccine targets. Ultimately, these findings have shed light on how bacterial pathogens may develop and spread and the researchers hope that this will result in development of better interventions to fight emerging bacterial diseases.
From Karolinska Institutet, Associate Professor Åsa Sjöling at the Department of Microbiology, Tumor and Cell Biology participated in the study. In addition to Swedish researchers, researchers from the Wellcome Trust Sanger Institute in the UK and universities in the United States, Germany and Japan took part in the project. The study was funded by grants from the Swedish Research Council, the Swedish Foundation for Strategic Research (SSF), the European Research Council, and the Wellcome Trust.
Identification of enterotoxigenic Escherichia coli (ETEC) clades with long-term global distribution
Astrid von Mentzer, Thomas R Connor, Lothar H Wieler, Torsten Semmler, Atsushi Iguchi, Nicholas R Thomson, David A Rasko, Enrique Joffre, Jukka Corander, Derek Pickard, Gudrun Wiklund, Ann-Mari Svennerholm, Åsa Sjöling & Gordon Dougan
Nature Genetics online 10th November 2014, doi:10.1038/ng.3145