Essays. FSF Columns

Some of the best and cleverest information-traders are some of the worst and most noxious bacteria. Such as *Staphylococcus *(boils). *Haemophilus* (ear infections). *Neisseria *(gonorrhea). Pseudomonas (abcesses, surgical infections). Even *Escherichia,* a very common human commensal bacterium.

When it comes to resisting antibiotics, bacteria are all in the effort together. That's because antibiotics make no distinctions in the world of bacteria. They kill, or try to kill, every bacterium they touch.

If you swallow an antibiotic for an ear infection, the effects are not confined to the tiny minority of toxic bacteria that happen to be inside your ear. Every bacterium in your body is assaulted, all hundred trillion of them. The toughest will not only survive, but they will carefully store, and sometimes widely distribute, the genetic information that allowed them to live.

The resistance from bacteria, like the attack of antibiotics, is a multi-pronged and sophisticated effort. It begins outside the cell, where certain bacteria have learned to spew defensive enzymes into the cloud of slime that surrounds them -- enzymes called beta-lactamases, specifically adapted to destroy beta-lactam, and render penicillin useless. At the cell-wall itself, bacteria have evolved walls that are tougher and thicker, less likely to soak up drugs. Other bacteria have lost certain vulnerable porins, or have changed the shape of their porins so that antibiotics will be excluded instead of inhaled.

Inside the wall of the tank car, the resistance continues. Bacteria make permanent stores of beta-lactamases in the outer goo of periplasm, which will chew the drugs up and digest them before they ever reach the vulnerable core of the cell. Other enzymes have evolved that will crack or chemically smother other antibiotics.

In the pump-factories of the i

Sometimes -- rarely -- a cell will come up with a useful mutation entirely on its own. The theorists of forty years ago were right when they thought that defensive mutations would be uncommon. But spontaneous mutation is not the core of the resistance at all. Far more often, a bacterium is simply let in on the secret through the exchange of genetic data.

Beta-lactam is produced in nature by certain molds and fungi; it was not invented from scratch by humans, but discovered in a petri dish. Beta- lactam is old, and it would seem likely that beta-lactamases are also very old.

Bacteriologists have studied only a few percent of the many microbes in nature. Even those bacteria that have been studied are by no means well understood. Antibiotic resistance genes may well be present in any number of different species, waiting only for selection pressure to manifest themselves and spread through the gene-pool.

If penicillin is sprayed across the biosphere, then mass death of bacteria will result. But any bug that is resistant to penicillin will swiftly multiply by millions of times, thriving enormously in the power- vacuum caused by the slaughter. The genes that gave the lucky wi

That genetic knowledge, once spread, will likely stay around a while. Bacteria don't die of old age. Bacteria aren't mortal in the sense that we understand mortality. Unless they are killed, bacteria just keep splitting and doubling. The same bacterial "individual" can spew copies of itself every twenty minutes, basically forever. After billions of generations, and trillions of variants, there are still likely to be a few random oldtimers around identical to ancestors from some much earlier epoch. Furthermore, spores of bacteria can remain dormant for centuries, then sprout in seconds and carry on as if nothing had happened. This gives the bacterial gene-pool -- better described as an entire gene-ocean -- an enormous depth and range. It's as if Eohippus could suddenly show up at the Kentucky Derby -- and win.

It seems likely that many of the mechanisms of bacterial resistance were borrowed or kidnapped from bacteria that themselves produce antibiotics. The genus Streptomyces, which are filamentous, Gram- positive bacteria, are ubiquitous in the soil; in fact the characteristic "earthy" smell of fresh soil comes from Streptomyces' metabolic products. And Streptomyces bacteria produce a host of antibiotics, including streptomycin, tetracycline, neomycin, chloramphenicol, and erythromycin.

Human beings have been using streptomycin's antibiotic poisons against tuberculosis, gonorrhea, rickettsia, chlamydia, and candida yeast infection, with marked success. But in doing so, we have turned a small- scale natural process into a massive industrial one.

Streptomyces already has the secret of surviving its own poisons. So, presumably, do at least some of streptomyces's neighbors. If the poison is suddenly broadcast everywhere, through every niche in the biosphere, then word of how to survive it will also get around.

And when the gospel of resistance gets around, it doesn't come just one chapter at a time. Scarily, it tends to come in entire libraries. A resistance plasmid (familiarly known to researchers as "R-plasmids," because they've become so common) doesn't have to specialize in just one antibiotic. There's plenty of room inside a ring of plasmid DNA for handy info on a lot of different products and processes. Moving data on and off the plasmid is not particularly difficult. Bacterial scissors-and-zippers units known as "transposons" can knit plasmid DNA right into the central cell DNA -- or they can transpose new knowledge onto a plasmid. These segments of loose DNA are aptly known as "cassettes."

So when a bacterium is under assault by an antibiotic, and it acquires a resistance plasmid from who-knows where, it can suddenly find an entire arsenal of cassettes in its possession. Not just resistance to the one antibiotic that provoked the response, but a whole Bible of resistance to all the antibiotics lately seen in the local microworld.

Even more unsettling news has turned up in a lab report in the Journal of Bacteriology from 1993. Tetracycline-resistant strains in the bacterium Bacteroides have developed a kind of tetracycline reflex. Whenever tetracycline appears in the neighborhood, a Bacteroides transposon goes into overdrive, manufacturing R-plasmids at a frantic rate and then passing them to other bacteria in an orgy of sexual encounters a hundred times more frequent than normal. In other words, tetracycline itself now directly causes the organized transfer of resistance to tetracycline. As Canadian microbiologist Julian Davies commented in Science magazine (15 April 1994), "The extent and biochemical nature of this phenomenon is not well understood. A number of different antibiotics have been shown to promote plasmid transfer between different bacteria, and it might even be considered that some antibiotics are bacterial pheromones."