Cell biologists at the University of Konstanz have discovered how specialised bacteria colonise human mucosal surfaces. Prof. Dr. Christof Hauck’s team is mainly interested in a mechanism known as exfoliation, i.e. the shedding of epithelial cells, which certain bacteria suppress in order to be able to effectively colonise mucosal surfaces.
The research results obtained by a team of cell biologists from the University of Konstanz led by Professor Dr. Christof Hauck have shed new light on mechanisms that enable bacteria to colonise the human body. The scientists provided experimental proof of evidence for the fact that certain human-restricted bacteria suppress the shedding of epithelial cells in order to effectively colonise human mucosal surfaces. The research results, which were recently published in the renowned scientific journal "Science", now put the rapid shedding of epithelial cells, also termed exfoliation, at the centre of scientific interest.
"If we are able to better understand the mechanism of exfoliation, in future we will be able to counteract the sophisticated tricks of bacteria and use this knowledge for preventive and therapeutic approaches," Professor Hauck explained. Colonisation of mucosal surfaces is the key initial step in most bacterial infections; many microbes initially colonise the mucosal surfaces of the human body, for example the throat, the intestines or the urogenital tract. It is not an easy task for the microorganisms to colonise the mucosal surfaces because the epithelial cells can be shed one after the other, just like the pages of a calendar. The constant regeneration of tissue, which is also termed exfoliation, prevents pathogens from colonising mucosal surfaces.
The research results obtained by the team of cell biologists led by Christof Hauck now show that specialised bacteria make use of sophisticated measures to counteract the shedding of epithelial cells: they trigger mucosal cells to better adhere to the surrounding tissue and make sure that the infected cells are unable to detach from the mucosa. The researchers have been able to show that the pathogens are not only able to suppress exfoliation of mucosal cells, but also that they are able to more efficiently colonise the mucosa.
The researchers investigated the bacterial colonisation of mucosal surfaces using highly specialised gonococci, which are the cause of gonorrhoea. "These bacteria are highly effective in colonising human mucosae and a prime example of pathogens that have adapted to humans. Gonococci are found exclusively in humans, and nowhere else in nature. This high degree of adaptation to a specific host is quite rare," Christof Hauck explained. The researchers discovered that the binding of these bacteria to certain receptors on the mucosal cells, known as CEACAMs (carcinoembryonic antigen-related cell adhesion molecule), suppresses the process of exfoliation.
The biologists found that the binding of the bacteria to CEACAMs triggers a signalling cascade in the cells, which leads to the stimulation of integrins. Integrins are receptors that mediate attachment between a cell and the tissue surrounding it, thereby acting as a kind of glue and preventing exfoliation. It is not yet clear why bacteria can easily target human mucosal cells and their CEACAMs, and suppress exfoliation. However, it is interesting to note that it is not only the pathogenic gonococci, but also some harmless throat-, nose and mouth colonisers that bind to CEACAMs. "We assume that the mechanism that leads to the suppression of exfoliation originally developed in order to enable the colonisation of mucosal surfaces by harmless bacteria, and potentially also by bacteria that had a beneficial effect for humans," said Professor Hauck.
Future investigations will focus on ways to manipulate the exfoliation mechanism in order to either prevent pathogenic bacteria from colonising the mucosae or enable beneficial bacteria to more effectively colonise the mucosae.
Prof. Dr. Christof R. Hauck
University of Konstanz
Department of Cell Biology
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