27 February 2012
Dr Ariel Blocker from the University's School of Cellular and Molecular Medicine, in collaboration with Professor Keiichi Namba (University of Osaka School of Frontier Biosciences, Japan) and Dr Luca Giuggiolli (University of Bristol, Centre for Complexity Sciences), has been awarded a £750k project grant from the UK Medical Research Council (MRC) to carry out research into how a dysentery-causing bacterium infects its human host. This is the largest single award ever received by her laboratory and it comes after several other productive MRC and Wellcome Trust awards in recent years.
The laboratory, which investigates the microbial secretion mechanisms that underlie how host protein functions are manipulated during infection, will study a secretion system of Shigella flexneri, the infectious organism responsible for bacillary dysentery, which is transmitted through contaminated food or water, or through human contact.
These protein transport organelles, which act as tiny "injection syringes", secrete protein toxins that alter host cell functions and hence facilitate infection. By studying the Shigella flexneri secretion machinery, known as a type III secretion system (T3SS), the researchers aim to design inhibitors of the injection machineries of these bacteria.
Such inhibitors, also known as “anti-virulence drugs”, could become a new type of broad-range anti-microbials in the continuing fight against infectious diseases. Such anti-microbials might ultimately complement or replace conventional antibiotics, to which resistance continues to increase at alarming rates.
Dr Blocker said: “In ten years, our laboratory has made major progress in understanding how the secretion systems are activated in these infectious organisms, which are critical in the virulence of many major human, animal and plant pathogens. Yet, many mechanistic questions remain about exactly how this occurs and about how these secretion systems are regulated. It is this work that this major grant will fund.
“By studying the complex function and structure of the toxin injection device that underlie the pathogenesis of Shigella flexneri bacteria, we hope to design new ways to treat this highly infectious disease, which is responsible, worldwide, for an estimated 165 million episodes of shigellosis and 1.5 million deaths per year, mainly in infants in developing countries and for which no vaccine is yet available. Such new therapeutics may also be useful to combat other bacterial pathogens that also carry T3SS as their key virulence device.”
Some of the project’s early findings have been accepted for publication in the Proceedings of the National Academy of Sciences (PNAS).
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