BioWorld International Correspondent

LONDON - The culprit responsible for teenage hours spent agonizing in front of the bathroom mirror before a date - the bacterium Propionibacterium acnes - might be defeated by the time today's babies start worrying about acne.

Last week, a team of researchers based in Germany published the complete genome sequence of P. acnes, the blueprint for finding out just how it causes the pimples and scars that plague many young people.

The group, led by Gerhard Gottschalk, head of the Gottingen Genome Sequencing Center at Georg-August-University Gottingen in Germany, set out to increase the sum of knowledge about the bacterium, which colonizes on the skin of every adult human being.

Holger Brueggemann, now a post-doctoral fellow at the Institut Pasteur in Paris, told BioWorld International, "All we knew was that P. acnes was present in acne lesions, but no one knew to what extent it was involved in generating the disease."

The results, he said, could lead to new therapeutic agents to fight P. acnes, perhaps by inhibiting some of the essential enzymes unique to the bacterium and thus slowing its growth rate.

An account of the findings appears in the July 30, 2004, issue of Science in a paper titled "The Complete Genome Sequence of Propionibacterium Acnes, a Commensal of Human Skin."

Acne affects up to 85 percent of all young people during their teenage years, with about 15 percent suffering so severely that they seek treatment from their doctors. Although current treatments with antibiotics, oxidative agents and the drug isotretinoin can help, resistance to antibiotics is growing, and, in any case, the acne returns when the treatment stops.

P. acnes also is known to play a role in a range of other diseases, including corneal ulcers, endocarditis, sarcoidosis, cholesterol gallstones and allergic alveolitis.

Sequencing the genome of P. acnes showed that it has a single circular chromosome of more than 2.5 million base pairs. Brueggemann and his colleagues identified more than 2,300 genes, many of which provide clues to how the bacterium causes its effects, and how it is able to grow in the skin.

Brueggemann said: "We were astonished to see the capability of the bacterium to digest human-derived substances. It can degrade many components of human skin tissue. It also has the genes to form pores in the membrane, and it has a huge array of lipases to degrade skin oils."

At least 25 different proteins are exposed on the cell surface of P. acnes, and they have domains that interact with human skin cells. The bacterium might be able to change its surface structure according to different environmental conditions by altering gene expression.

Several genes have been identified, which are "hot candidates in triggering an immune response," Brueggemann added. That fits in with the findings of several earlier studies, which have shown that people with severe acne have both increased cellular immunity and increased humoral immunity.

Gottschalk said: "The discovery of genes, which appear to be capable of making proteins that can stimulate the immunogenic response and inflammatory processes, is one of the most interesting findings. The microflora on the skin is largely controlled by the shortage of water in the pores. P. acnes lives in the lower portion of the skin follicles, and triggering inflammation stimulates sweat production, which delivers the nutrients and water that the bacterium needs for growth."

Some of the genes are known to belong to groups such as heat-shock proteins. One gene resembles another that is present in Mycobacterium tuberculosis and Mycobacterium leprae, which is involved in bringing about the symptoms of multibacillary leprosy.

Brueggemann is optimistic that it might soon be possible to design new therapeutic agents for acne.

"These agents would not need to kill the bacterium, just control its growth," he said. "The problem is caused by the increased skin oils that are present following puberty, and because these provide the bacteria with lots of nutrients, their growth rate is high."

Gottschalk's team now is beginning a collaboration with researchers at the University of Ulm in Germany. They plan to investigate the sequence further and will focus on identifying which genes the bacterium expresses under different environmental conditions. The group also wants to establish which proteins are involved in interacting with the host cell. One of their first aims will be to develop a model to study the interaction of the bacterium with the skin.

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