Revolutionary study unearths vital new information about Buruli ulcer, the third most common bacterial infection after tuberculosis and leprosy.
Buruli ulcer is an emerging tropical disease caused by the Mycobacterium ulcerans bacterium, an organism which belongs to the family of bacteria that cause tuberculosis and leprosy. Around 5,000 cases are recorded a year, the majority in poor rural communities in west Africa, Australia and southeast Asia where the infection is thought to be picked up through bathing in slow running water.
The infection causes large and unsightly ulcers which can lead to lifelong disfigurement and disability. Antibiotics can be used to treat Buruli ulcer, but they take a long time to work and few people with the disease can afford to pay for extended stays in hospital.
A new study, led by the University of Surrey and published in PLOS Pathogens, pinpoints the specific way in which the toxin synthesised by the Mycobacterium ulcerans bacterium – called mycolactone– inhibits the body’s production of proteins that are responsible for the immune response to the disease. It does this by blocking their transport through a pore-like structure called the Sec61 translocon that controls entry into the endoplasmic reticulum. This network of tube-like membranes carries out many essential functions, including targeting proteins for secretion.
The groundbreaking findings will be transformative to the understanding of this disease as they fully explain the pathology of Mycobacterium ulcerans for the first time, and will enable scientists to develop new diagnostics and predict the way the disease might react to potential new treatments.
The work was funded by a £300,000 grant from the Wellcome Trust.
Dr Rachel Simmonds, Lecturer in RNA Biology, who led the research, said, “As far as we know, every living organism on the earth today has a version of the Sec61 translocon. The fact that mycolactone inhibits such a fundamental cellular process is very exciting – not only will it help those with Buruli ulcer but we can use it as part of our molecular toolkit to better understand many other diseases that use this same pathway.”