Genotyping epidemic Shigella sonnei

Lead Research Organisation: University of Strathclyde
Department Name: Inst of Pharmacy and Biomedical Sci

Abstract

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.

Technical Summary

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.
 
Title a collection of phylogenetic and pathogenic diverse Shigella sonnei strains. 
Description through our genotyping study, it becomes clear that Shigella sonnei is highly diverse in terms of phylogenicity and pathogenicity. In particular some isolates carry virulence plasmid with reduced virulence. Circulation of these less virulent isolates in developed countries may offer natural immunisation to the population 
Type Of Material Database/Collection of Data/Biological Samples 
Year Produced 2009 
Provided To Others? Yes  
Impact Further collaborations are initiated among a number of international instiutes. 
 
Description Application of gold nano-rods in Biology (Dr Chen, Y., Department of Physics, University of Strathclyde) 
Organisation University of Strathclyde
Department Department of Physics
Country United Kingdom 
Sector Academic/University 
PI Contribution Dr Chen and I are respectively responsible for Optical Physics and Cell Biology aspects of the project.
Collaborator Contribution Dr Chen Y and I equally contribute to this potentially productive project, which will lead to a broad spectrum of application of nano-technology in Biology.
Impact We have published one paper (J Biomed Opt. 2010 Mar-Apr;15(2):020504) and recruited a PhD student to carry on the project.
Start Year 2007
 
Description Development of Shigella-HPV vaccine (Professor Yili Wang, Xi'an Jiao Tong University China) 
Organisation Xi'an Jiaotong University
Department Institute of Immunopathology
Country China 
Sector Academic/University 
PI Contribution The aim of this collaboration is to develop live attenuated Shigella sonnei carriers which express the L1 proteins from 3 prevalent HPV types16, 18 and 58.
Impact For the purpose of vaccine development we have gathered and published the epidemiological and clinical prognosis data of Type 58 HPV in Han population in China (Clinical Oncology 2009. 21: 768e774). A Chinese PhD student have been working in Strathclyde for 2 years (20010-2011) in constructing the vaccine strains.
Start Year 2006
 
Description SIPBS University of Strathclyde (Dr Veronique Seidel) 
Organisation University of Strathclyde
Department Strathclyde Institute of Pharmacy & Biomedical Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution Dr Seidel has long term interesting in isolation of natural products that exhibit anti-microbial activity. I have initiated conceptually new application of exploiting the natural product; searching for their potential in modulating pathogen-host cell interaction for the benefit of the host.
Impact Xu D et al., J Med Microbiol. 2011 Nov;60(Pt 11):1626-32.
Start Year 2009
 
Description SGM symposium 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Primary Audience Health professionals
Results and Impact Over 100 microbiologists were attending the symposium each year.

broader interests in genotyping Shigella sonnei and other pathogenic bacteria were attracted.
Year(s) Of Engagement Activity 2009,2010
 
Description UK-China Bacterial Pathogen Symposium 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Primary Audience Health professionals
Results and Impact 200 professional were present.

interesting discussions were sparked.
Year(s) Of Engagement Activity 2009