Post doctoral Research Fellow (ECR), Monash University
Understanding how the bacterium Clostridium difficile causes severe disease
Infection with the bacterium Clostridium difficile is a major global public health concern. C. difficile causes severe gastrointestinal illness and death in humans, particularly the elderly, and is the most significant cause of hospital-acquired diarrhoea worldwide. C. difficile infection (CDI) is often induced by treatment with antibiotics that are used to treat other, unrelated, medical conditions. These antibiotics disrupt the normal gut microbiota, leaving a patient susceptible to infection. Rather incongruously, treatment of CDI also requires antibiotics, which prevent the re-establishment of the microbiota. Consequently, ~30% of patients experience disease relapses. The virulence of C. difficile strains involves the action of two major toxins, toxin A (TcdA) and toxin B (TcdB). Our laboratory at Monash University has studied the role of these toxins during infection and has examined in detail how they cause disease. Our results provide clear evidence that TcdB is the main mediator of gut damage, with TcdA inducing little disease in a mouse model. Importantly, we have shown that infection with TcdB-producing strains not only damages colonic tissue, but also causes damage in organs outside of in the intestines, including the thymus, lymph nodes, spleen and kidneys. It is known that C. difficile infection in humans causes Multiple Organ Dysfunction Syndrome (MODS), a severe complication of CDI that is associated with high mortality rates. Our results clearly show that TcdB is associated with systemic and severe disease in mice and may therefore be responsible for the onset of MODS. My work aims to determine whether damage to other organs is directly mediated by TcdB or is a consequence of toxin-induced ‘leaky gut’ that allows the spread of gut contents from the colon to other organs outside of the gut.
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