Genotyping epidemic Shigella sonnei

Dr. Yu is proposing to carry out further research, in order to combat the Shigella bacteria infection, which affects 160 million people per annum worldwide; resulting in 1.1 million deaths of which most affected are children; under 5 years old. The infection could be so severe; the inflammation in the large intestine and rectum cause bleeding and cramps and patients experience excruciating pains, facing death. To make things worse, most of the epidemic strains are now resistant to all antibiotics available to date. Dr. Yu has carried out extensive research on this subject since 1997 and has been co-authored several important papers on Shigella genome research. His attention is now turning to S. sonnei, which seems to be a real threat to modern civilisation, as it is already very prevalent in developed countries, including those newly industrialised countries such as Republic of China, Thailand, and Iran. To combat the S. sonnei infection, Dr. Yu will investigate the genetic variation among S. sonnei strains of a global collection dated back to 1940s by use of a novel Solexa multiplex sequecing approach and the cutting edge instrument LightCycler 480. It is hoped to find the strain?s origin and route of evolution, how they acquire antibiotic resistance, and in particular, why young children are so susceptible to S. sonnei infection; this life threatening disease. Dr. Yu is confident, that this study will succeed and the new knowledge obtained will help epidemic surveillance, early diagnosis, and treatment and prevention of Shigella infection.

Shigella sonnei belongs to the Shigella/EIEC pathovar and has emerged to be the most prevalent species to cause bacillary dysentery in developed countries not only in Europe and North America but also in newly industrialised countries such as Korea, Republic of China, Thailand and Iran. Furthermore, S. sonnei infects more young children (0-5 years old) compared to other species, and most of the epidemic strains are multi-drug resistant due to spread of integrons. S. sonnei contains only one serovar but has many biotypes and their origin and evolution are poorly understood. To combat S. sonnei infection, a novel and effective genotyping scheme is urgently required because current available molecular typing methods have limited discrimination power to reveal global diversity, population genetic structure and evolutionary history of S. sonnei, all of which are important for disease surveillance and epidemiological investigations. Therefore, the proposed project is aimed at (1) development of a single nucleotide polymorphism (SNP)-based multilocus sequence typing (MLST) scheme to type a global S. sonnei collection for explanations as to why S. sonnei is prevalent in developed countries and more susceptible to young children, and to reveal the evolutionary history of this pathogen, and (2) automation of latest Roche LightCycler 480 instrument to detect informative SNPs that mark the current prevalent epidemic phylogenetic groups for S. sonnei surveillance, and (3) construction of a web-based service to facilitate global epidemiologic studies and disseminate new knowledge.