Pathogens & People: Pathogens, as

with people, come in all shapes and

sizes

By EDWARD McSWEEGAN, For The Capital

Published October 05, 2008

So, naturalists observe, a fleaHas smaller fleas that on him prey;And

these have smaller still to bite 'em,And so proceed ad infinitum.

These lines from Jonathan Swift's classic poem, ''a Rhapsody,'' about how the
little are eaten by the big and the big by the bigger is a rule of nature that also
applies in the very small world of microorganisms. You might not think microbes
have a lot of size variation, but they do, and size matters. It determines who
infects whom.

Let's look at the scale of small things. Our red blood cells are about 10
micrometers in diameter. Common E. coli bacteria are two micrometers long.
The smallpox virus measures about 0.2 micrometers, and the bacteriophage virus
that infects E. coli is 0.06 micrometers. As a rule, human cells are bigger than
bacterial cells, which are bigger than viruses. A microscope usually is needed to
see cells and an electron microscope is needed to see the ghostly geometric
shapes of viruses. But there are exceptions.

Epulopsicium fishelsoni is one such exception. At 250 micrometers, this giant,

cigar-shaped bacterium can be seen with the naked eye. The smallpox virus is
another microbial giant. Smallpox viruses can be seen in infected cells with a
high-quality light microscope.

Smallpox was the big boy in the viral neighborhood until 2003 when the
Mimivirus was discovered. Because of its size (0.4 micrometers) and genetic
complexity (900 genes of double-stranded DNA), Mimivirus initially was
mistaken for a bacterium. As with the bacteria that cause Legionnaire's disease,
the Mimivirus was found lurking inside amoeba, which were living in the water of
cooling towers. And like the Legionella bacteria, Mimivirus also causes human
disease. In 2004, one of the French scientists studying Mimiviruses became
infected and developed pneumonia. Recent research has found that about 10
percent of pneumonia patients have antibodies to Mimivirus.

The giant Mimivirus uses water-borne amoeba to replicate, and perhaps as a

Trojan horse to get into human lungs to cause pneumonia. It is an interesting
example of the sometimes complex interactions of pathogens, environments and
hosts. But what's really interesting is that Mimivirus is sometimes the victim of
yet a smaller pathogen.

In August, French scientists reported Mimiviruses can be infected by a tiny virus

called a virophage. A Mimivirus infects an amoeba in order to make more copies
of itself, but can have its replication hijacked by an infecting virophage, which
then makes more copies of itself at the expense of the Mimivirus. (Who knew so
much was going on inside an amoeba?)

Traditionally, viruses have not been considered "alive" because they lack
metabolic functions and they spontaneously assemble like someone's clever piece
of nanotechnology. So the discovery of viruses that infect viruses has a number of
people asking, "How can a virus - something that supposedly isn't alive - become
sick?"

It may be an important question because the oceans seem to be full of giant

viruses such as the Mimivirus. These viruses may be common infectious agents of
ocean plankton, even as they also serve as hosts to smaller infectious virophages.
Thus the tiny virophage and the larger Mimivirus may affect plankton
populations, which in turn affect ocean nutrients, fish populations and climate.

If these novel viruses play a role in ecology they also may have played a role in
evolution.

One of the obvious distinctions between our cells and bacterial cells - besides size
- is complexity. Our cells have numerous organelles (tiny organs), and a discrete
nucleus filled with DNA. Some of these organelles, such as the energy-producing
mitochondria or plant chloroplasts responsible for photosynthesis, probably
evolved from primitive bacteria that got into primitive cells and decided to stay.
But where did the cell's DNA-filled nucleus come from?

One theory suggests the nucleus evolved from large, infecting DNA viruses such
as Mimivirus. But the opposite may be just as likely: that a lost nucleus devolved
into the various DNA viruses we find today.

The idea that our cells evolved from primitive infecting bacteria and viruses is
interesting biology, but it also may have some implications for disease.

If our cells' mitochondria are the remnants of primitive bacteria, could they
become infected by an exotic virus in the same way phage viruses infect bacteria?
At least one such mitochondria virus (mitovirus) has been found in the fungus
that causes Dutch elm disease. Could similar mitoviruses be found infecting
human mitochondria and causing unexplained degenerative diseases?

"These kinds of microorganisms should be kept in mind for the future," wrote the
editor of the MicrobiologyBytes blog. Good advice, because we know big fleas
have little fleas, and big viruses have little viruses, and so, ad infinitum.

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Dr. Edward McSweegan has a Ph.D. in microbiology and lives in Crofton. He

works on and writes about infectious disease issues. He may be contacted at
mcsweegan@nasw.org.