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By Nancy Humphrey

Say Chlamydia pneumoniae and before you get to pneumoniae most people think of a sexually transmitted disease.

"As soon as people hear the name Chlamydia their ears shut down," said Dr. Charles W. Stratton, associate professor of Pathology. "They either don't hear or don't understand the second part - pneumoniae. They think of Chlamydia trachomatis, a common cause of sexually transmitted diseases. c is the one that's not fun to catch."

The Chlamydia pneumoniae (C. pneumoniae) organism, first described in 1988, is not the sexually-transmitted type. It is an airborne organism that you get from breathing after a person carrying the organism has coughed.

"They float around as droplet nuclei, similar to TB. People cough and up come these infectious bodies. They float around a room. You breathe. In they come and now you've got your own."

It's how they work inside the body that Stratton, Dr. William M. Mitchell, professor of Pathology, and colleagues have been looking at for the past five years.

The study of the organism has intensified as Stratton's colleagues at Vanderbilt and other medical centers around the country, including Johns Hopkins and The Mayo Clinic, look at the role of Chlamydia in diseases such as Multiple Sclerosis, Rheumatoid Arthritis, Pyoderma gangrenosum, Coronary Artery Disease and Interstitial Cystitis.

Stratton said that Chlamydia is sneaky. When viruses invade a cell, if they are active, they integrate in the human DNA and basically take over the cell.

"They tell the cell, 'Ok, today, we're going to do nothing but make viruses and the cell often dies in this process," Stratton said.Chlamydia works in a different way. First, when you breathe in Chlamydia, it can infect the ciliated cells, the cells lining the airways. Ciliated cells are like an escalator that moves mucus along. Chlamydia can paralyze the ciliated cells because it steals their energy. So the host has a nasty respiratory infection.

When you have an active infection of any kind, the body has an immune response to it. Part of the immune response is that monocytes and macrophages try to engulf the pathogen and kill it.

But they can't always kill Chlamydia. Instead, they disseminate the organism to peripheral blood mononuclear cells and the organism can silently infect other cells in the body. "With these cryptic infections, you don't have symptoms. And because Chlamydia isn't really a virus, when it's causing a cryptic infection, it's metabolizing. It's eating, drinking, singing and dancing. It's alive."

Since Chlamydia can't make its own energy, it has to steal energy from the human cell. This means the chlamydia-infected cell doesn't work well. "If Chlamydia is actively metabolizing in a cell, it's up to no good. It's stealing energy. I can't picture anything good coming from chlamydia being in a human cell."

Chlamydia also likes to infect endothelial cells, the cells that line blood vessels. When there's inflammation in the body, there often is angiogenesis, meaning new blood cells are formed. And Chlamydia is drawn to those cells. So if Chlamydia is in the peripheral blood mononuclear cells and there's an inflammation in the host's body, you're "unlucky," Stratton said. Any secondary inflammatory process could become secondarily infected by Chlamydia no matter what the source of the inflammation, Stratton said.

"Now you've got a chronic problem," Stratton said. "Now you've got a major chronic infection in the tissue, whether it's the brain (MS) or in the joints (Rheumatoid Arthritis).

"If you have inflammation, a spider bite, a viral joint infection, viral meningitis or encephalitis, it doesn't matter what it is, if a Chlamydia-infected cells happens to end up in that inflamed area, you may have just started yourself a Chlamydia farm."

Stratton said this doesn't necessarily mean that Chlamydia causes the disease, but it may play heavily into how the disease progresses. There may be many causes of MS, Rheumatoid Arthritis or other diseases in which Chlamydia is believed to play a role.

"One thought is that Chlamydia is not the cause of anything other than pneumonia but once it causes a lung infection and gets into your peripheral blood mononuclear cells, it's available to cause secondary infections in other tissues if the infected white cells happen to go to those tissues.

"It may be that MS is an infection of the brain that is caused by viruses, and most people who get that viral infection of the brain have a headache for a week, then get better. If you happen to have Chlamydia, however, you may go on and have a chronic illness.

Scanned in from "The Economist - 21st March 1998

ATLANTA

Evidence is accumulating that many chronic ailments, including one that kills, are caused by bacteria.

Bugged by disease.

Evidence is accumulating that many chronic ailments, including one that kills, are caused by bacteria.   MOST people, in the West at least, probably think of a bacterial infection as something that is over with quickly. You catch it, you are treated, you get better—or else you die. There are exceptions, of course.

Leprosy brings lingering misery, and tuberculosis can last for years. In general, though, bacterial diseases appear to be short sharp shocks that can be dealt with by a highly tuned immune system, perhaps backed up with a dose of antibiotics.

It may come as a surprise, therefore, that asthma, arthritis, hardening of the arteries and a number of other diseases which sometimes nag on for as long as a person lives may also be the result of bacterial infections. Exploring the role that bacteria play in these ailments is a new topic in medicine. That is why, although the diseases themselves are hardly novel, the recent International Conference on Emerging Infectious Diseases, held in Atlanta by America’s Centres for Disease Control ( CDC ), devoted a session to them.

Now you see it...

The session’s principal speaker was Gail Cassell, who works at Eli Lilly’s laboratory in Indianapolis on a group of bugs known as the Mycoplasmas. (Much of CDC ’s own effort in the field is co-ordinated by Siobhan O’Connor.) Dr Cassell explained how the field had arisen, some of the difficulties and some recent findings.

The first chronic complaint found to have an unexpected bacterial cause was stomach ulceration. The evidence that ulcers are triggered by a bug called Helicobacter pylori had been accumulating since the 1970s. America’s medical establishment (ie, the National Institutes of Health) officially accepted the idea in 1994. This encouraged others who were looking for hitherto-unsuspected connections between infections and disease.

Meanwhile, a number of new biochemical tools capable of identifying so-called “fastidious” bacteria—bugs that are difficult to extract from infected tissue and grow in cultures for identification—were being developed to aid the search. Bacterial genes can now be detected in infected tissues by using in situhybridisation, in which small DNA “probes” attached to fluorescent molecules stick to the relevant genes, or with advanced versions of PCR (the polymerase chain reaction, which allows small numbers of DNA molecules to be multiplied into quantities that can be analysed).

Bacterial proteins, too, can be identified and analysed in infected tissue by combining new techniques for the production of antibodies with the expanding science of immunocytochemistry (which looks at the reactions to those antibodies of individual components of cells). The days when an infection could be identified only by growing a culture in a Petri dish are past.

Helicobacter’s activities seem, so far, to be confined to the stomach (though the bacterium has now been implicated in cancer there, as well as in its ulcers). A number of other bacterial suspects appear, however, to have broader effects. Conversely, similar symptoms can be produced by a variety of organisms.

For example, four different sorts of food-borne bug—Salmonella, Shigella, Campylobacter and Yersinia—can cause reactive arthritis, a painful inflammation of the joints that may last months or even years. And the same bacteria also cause Reiter’s syndrome, a disease whose victims suffer not only inflamed joints, but also inflammation of the eyes and the urinary tract.

Reactive arthritis is not, however, caused only by what you eat. It can also result from other pleasures. It may be provoked by infection with Chlamydia trachomatis, a sexually transmitted denizen of the genital tract, and Ureaplasma urealyticum and Mycoplasma fermentans, two other inhabitants of the genitals. Breathing can be hazardous too. Mycoplasma pneumoniae, a cause of pneumonia, as its name suggests, is also implicated in reactive arthritis. And arthritis of a somewhat different sort sometimes follows Lyme disease, an infection caused by Borrelia burgdorferi which is passed on by tick bites. Chlamydia trachomatis also causes blindness, while its cousin, Chlamydia pneumoniae, is implicated in asthma. Mycoplasma pneumoniae also appears to be involved in asthma. But perhaps the most worrying of all these findings is the suspected link between Chlamydia pneumoniae and atherosclerosis (hardening of the arteries). Over the past few years, research done in Finland, Italy, Britain, Argentina and America has confirmed that this bacterium likes to inhabit the fatty “plaques” which accumulate on the insides of the blood-vessel walls when arteries harden. One inference is that the bacteria may not merely be living in the plaques, but creating them.

There is a risk to this kind of reasoning, of course. The studies done so far clearly show a greater risk that someone will suffer a heart attack if antibodies to Chlamydia are present in his blood stream (indicating that the immune system is reacting to the bacterium’s presence), or when its DNA is found in his clogged arteries (it is definitely in the “fastidious” category when growing in arterial plaques, and has only rarely been cultured from them). But this does not prove Chlamydia is causing heart disease. It could simply be that the bugs like to live in plaques, but that those plaques were caused in the first place by something completely different. And even the strongest proponents of the idea that atherosclerosis is an infection do not claim Chlamydia is a sufficient cause by itself; diet and genes are also involved.

But there are at least two reasons to believe that correlation, in this case, reflects causation. First, using antibiotics to treat an atherosclerotic patient who has had one heart attack reduces the risk of his suffering a second. (Rheumatoid arthritis, the most common arthritic variety, also responds to antibiotics in some patients, leading researchers to suspect that it, too, may sometimes be provoked by bacteria.) Second, research has come up with the glimmer of a mechanism.

A recent experiment by Robert Molestina at the University of Louisville, in Kentucky, has shown that infecting endothelial cells taken from the walls of coronary arteries with Chlamydia stimulates the production of molecules called chemokines. That is not surprising, since the role of chemokines is to attract disease-fighting white blood cells called neutrophils and monocytes to the blood-vessel walls. Once there, however, these blood cells invade the endothelium, causing it to become inflamed.

Such inflammation is, in fact, a normal response to bacterial infection. The curious question is why the inflammation would become chronic in atherosclerosis, when in the case of most infections it is transient.

The most likely explanations are that the immune system is unable to clear the infection completely or that the site is peculiarly susceptible to reinfection, causing more damage each time. The bacteria, in other words, keep proliferating and the white cells keep coming. But whatever the cause, since another effect of inflammation is to attract platelets (fragments of blood cells that cause clots to form) to the area, the creation of a clot, with the attendant risk of a heart attack or stroke, is a common consequence of this continual inflammation.

Solve the problem of chronic inflammation, then, and a cure for atherosclerosis may come closer. But chronic inflammation is not restricted to the arterial walls. It appears to be the linking factor of many of these diseases. Arthritis is inflammation of the joints. Crohn’s disease (also suspected of being caused by bacteria) is an inflammation of the bowel. Ulcers are inflammations of the stomach. And so on.

Ironically, this common feature makes testing whether a particular disease is bacterial more difficult. Applying antibiotics, as has been done for atherosclerosis and arthritis, is the obvious experiment. But many antibiotics are also anti-inflammatories, which makes the results ambiguous.

If, nevertheless, a wide range of diseases now put down to the general process of ageing do turn out to be infections, a new field of treatment will open. Over the past few years, drug companies have been reluctant to invest in new antibiotics. Soon they may change their minds. Vaccines against germs which have been regarded as unworthy of attention might also be developed if such germs are shown to cause serious diseases. In future, therefore, it may be possible to pop a pill or have a shot to keep you both free of heart disease and lithe of limb.

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