Dissecting_the_genetic_basis_of_melioidosis_infection_II. Dissecting_the_genetic_basis_of_melioidosis_infection_II

Melioidosis is a rapidly progressing and frequently fatal infectious disease caused by a soil bacterium Burkholderia pseudomallei (Bp). Healthy individuals living in disease hotposts such as northeast Thailand develop serological evidence of bacterial exposure from early childhood. However, not all exposure leads to disease and infection can have variable outcomes; suggesting that there may be bacterial, host or environmental components that influence disease acquisition and severity. To identify genetic determinants in bacteria and hosts, we have been collecting blood samples from melioidosis patients and paired clinical B. pseudomallei isolates from patient specimen, as well as environmental B. pseudomallei from each patient household. In this part of the study (Dissecting the genetic basis of melioidosis infection II), we plan to sequence 600 clinical Bp isolates. The newly sequenced 600 bacterial samples will be combined with existing data (totalling 2,500 genomes) to power bacterial genome-wide association study for bacterial factors associated with host mortality. Moreover, this subset of 600 bacterial samples are linked to human host RNA data; thereby providing a unique opportunity to interogate host-bacterial interactions. A catalog of genetic markers associated with host mortality could rationalise vaccine design to target the most harmful bacterium and most susceptible host. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/