15 March 2012
Candida albicans can live inside the human body for a long time without any problems when suddenly, they turn on us and cause disease. Why this happens was the subject of a NIH-funded research project which has opened up a new line of oral microbiological enquiry.
In May 2008, the Sunday Telegraph magazine ran an article about fungal infections in which research at Bristol University’s Dental School was highlighted. One of the best known fungal infections is thrush, caused by Candida. This affects warm, moist areas such as the mouth and genital region, and sometimes the surface of the skin. Also commonly known as yeast infections, these conditions are uncomfortable and irritating at best in a healthy person, but for someone whose immune system is weak or who is vulnerable after surgery, they can be deadly. Many people have suffered such infections at one time or another, which is why Candida generates considerable interest from a public health perspective.
Howard Jenkinson, Professor of Oral Microbiology and Head of Research for the School of Oral and Dental Sciences, has been funded by the US National Institutes for Health (NIH) since 2006 for research into Candida albicans — the species of Candida that causes most infections.
“Candida albicans are a big concern in public health” said Howard. “The medical sciences community has been seeking to develop new ways of combating them, but the newer drugs can be very expensive and so not available for universal use. Candida albicans have also become quite resilient to antimicrobial agents. As a result, once they are in the body, they are very difficult to get rid of. So, one of our research questions was whether we might be able to reduce the ability of such organisms to colonise humans in the first place, and so stop disease being so prevalent.”
Candida can live inside the human body for a long time without problem, but they can suddenly turn on us and cause disease, usually in response to a change in diet, hormones or impact on the immune system. When Candida becomes pathogenic — i.e. likely to cause disease — it grows filaments known as hyphae that are able to penetrate the body tissues. The organisms can cause painful conditions such as ‘sore mouth’ in denture users, where they grow in between the denture and the palate. While denture wearers can apply an anti-fungal paste to help get rid of the infection, they usually end up having to obtain new dentures because the hyphae penetrate the denture material. However, Candida may lead to more serious problems if the fungi get into the blood stream and infect the organs. This condition, known as candidaemia, can be fatal.
“Candidaemia has about 50 per cent mortality rate” said Howard. “Older people and those with weakened immune systems are particularly prone to it.”
Howard's work has observed that Candida albicans interacts very closely with many different bacteria in the human body. Now it is understood that when an infection occurs, it often involves a number of different organisms living together. Hence antibiotics or other treatments that tend to kill specific types of microbe may not work effectively.
“We have developed biophysical models to understand the signalling that takes place between yeast and bacteria in producing infections” said Howard. “These models look at how the organisms grow together by mimicking conditions in the body. We do this by flowing saliva though glass cells, in which Candida and bacteria are growing together. While the focus of this work is oral infection, there may be offshoots from our research that apply to Candida infections in other parts of the body.”
The models were developed with colleagues Dr Michele Barbour from the Dental School in collaboration with physicist Mervyn Miles from the University's Nanoscience and Quantum Information Centre. Specifically, the research was interested in molecular interactions between Candida albicans and other bugs carried in the mouth. For example, Streptococcus bacteria were found to incite pathogenic behaviour in Candida albicans when growing alongside.
Research findings have been published by way of several academic papers. One paper led to a feature in a US science magazine, while another was picked as Journal Editor's choice– which meant that both papers had greater impact outside the journals in which they were originally published. This work, along with studies in other laboratories, is opening up a new area of microbiology research termed polymicrobial diseases. These are caused by microbes interacting with each other and stimulating pathogenic changes.
“We are hoping to build on these findings, with renewed funding of $2 million from the National Institutes of Health, to study the relationship between Candida albicans and periodontal (gum and jaw) disease. There is now evidence showing that Candida albicans may be involved alongside bacteria in dissolving away bone, causing teeth to drop out” said Howard. “The ultimate aim would be to develop new pharmaceutical products that can stop interactions taking place between Candida and other microbes.”
Howard Jenkinson can be contacted by email: firstname.lastname@example.org
Please contact Laura Greenwood for further information.
Cells of the Streptococcus bacteria (stained green) interacting closely with hyphae (stained blue) formed by the fungus Candida albicans
Image by Lindsay Dutton, Angela Nobbs and Mark Jepson
We have developed biophysical models to understand the signalling that takes place between yeast and bacteria in producing infections. These models look at how the organisms grow together by mimicking conditions in the body.