A process called sporulation that lets the harmful bacterium Clostridium difficile (C. difficile) thrive and propagate inhospitable conditions is controlled by epigenetics, factors impacting gene expression beyond the DNA genetic code, scientists at Mount Sinai's Icahn School of Medicine study. This is the first discovery that sporulation in any bacteria is driven by epigenetics. Their research, published in Nature Microbiology on 25 November, opens up a new window for the development of treatments for this devastating infection.
C. Difficult infects almost half a million people every year, causing severe diarrhoea and killing just under 10% of those over the age of 65 who get it. Bacterial spores, which are spread through faeces, are extremely resilient and can survive for weeks or months outside the body, infecting individuals that come into contact with contaminated surfaces.
The C has been so common and devastating since the infection. The difficult genome has been well studied, but Gang Fang, PhD, Associate Professor of Genetics and Genomics at Mount Sinai's Icahn Institute for Data Analytics and Genomics and Senior Author of the study, says he and his collaborators have taken a different approach to their work. "We wanted to study beyond the bacteria's genetic code and investigate whether chemical changes were made to the genome," Dr Fang said. Although these epigenetic chemical changes, called methylation, do not change a gene's structure, they may modify the behaviour of a particular gene to make it more or less functional, which has profound effects on the function of the organism.
In 2012, Dr Fang's team pioneered the use of third-generation DNA sequencing to map bacterial epigenetic factors and began studying C. Difficult 2015 epigenetics. First, C was isolated from the team. Difficult from faecal samples of 36 patients who had been infected with the intensive care unit (ICU) at Mount Sinai Hospital. They studied the specimens and found a particular pattern of epigenetics that was strongly maintained in all the samples. Next, about 300 C was checked. Difficult genomes from GenBank, the National Institutes of Health's genetic sequence database, found that all shared the same gene responsible for the epigenetic pattern found in patients with ICU.
Suspecting this epigenetic mechanism played a crucial role in bacteria development, Dr Fang's team worked on two subsequent C experiments. Hard sporulation and C-infected mice. Difficult, with Aimee Shen's laboratory, PhD, Associate Professor of Molecular Biology & Microbiology at Tufts University Medical School and Co-Senior Author of the research, and with Rita Tamayo's laboratory, PhD, Associate Professor of Microbiology and Immunology at North Carolina University, Chapel Hill. For one experiment with mice, the researchers found that as much as 100 times fewer bacteria were present after 6 days compared with unaltered bacteria when they blocked the gene responsible for the epigenetic sequence.
Dr Fang says the results in these experiments highlight the importance of epigenetics in the study of disease bacteria and drug development.
Besides offering new epigenetic insights into C's study. Dr Fang hopes that this work would inspire future analyses of the epigenetic properties of bacteria, both challenging and potential targets for drug
Tags : infection, epigenetics, Sporulation , bacteria, harmful bacterium, Clostridium difficile,