Big Bugs- Little Bugs

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. --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 [email protected].