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 situ
hybridisation, 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 inflam mation 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 g enitals.
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 childhood asthma and
adult emphysema. 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.
