By David N. Leff

Believers in UFOs and visits to earth by alien mentors from outer space may have a field day with an editorial in today's Science, dated April 24, 1998.

The item, titled "Versatile gene uptake system found in cholera bacterium," notes that "Vibrio samples stored since 1888 show that the [gene uptake system] predates antibiotics."

The UFO angle is that the pathogen, the commentary continues, "may have adapted that [gene uptake system] to acquire antibiotic resistance genes." Can this mean that the ancient microorganism anticipated the 1950s advent of antibiotics by over half a century?

No such luck.

The editorial accompanies a research report titled "A distinctive class of integron in the Vibrio cholerae genome." Its senior author, microbiologist Julian Davies, told BioWorld Today: "We didn't find an antibiotic resistance factor in that 1888 Vibrio strain. What we did find in it is the mechanism by which bacteria pick up resistance genes. And that presumably was not put into operation until the 1950s, when antibiotics were first being used."

What he found "was a particular structure known as an integron, which we now know to be one of the principal factors in the acquisition or capture of resistance genes in Gram-negative bacteria."

Davies is a pioneer biotechnologist and professor emeritus of microbiology at the University of British Columbia, in Vancouver. He observed, "One of the reasons we wanted to analyze this 19th-century strain, so long before antibiotics came into use, was precisely because there was no selection pressure on the bacteria to acquire antibiotic resistance."

French microbiologist Didier Mezel, the paper's lead author, was a visiting scientist in Davies' laboratory in Vancouver. He is a senior investigator at the Pasteur Institute, in Paris. That's where the isolates of V. cholerae and another virulent strain, V. Metschnikovii, along with many others, have been stored since 1888 as freeze-dried cultures. The latter Vibrio is named for Ilya Metchnikov, the celebrated Russian-French scientist who headed the Pasteur Institute from 1888 until his death in 1916.

"V. Metschnikovii causes acute intestinal infection in birds, particularly chickens," Davies recalled. "We could not find a human strain that was that old."

Nuts, Bolts Of Bacterial Gene-Sharing

He described the bacterium's "very simple but pervasive system that is capable of capturing alien genes:

"It requires the enzyme integrase, a gene encoding that integrase, and a gene attachment site situated close to the integrase. Also," Davies continued,"it requires that the gene that is picked up have an appendage that will recombine with the attachment site next to the integrase gene, under the direction of the enzyme. That's all it needs."

Mezel told BioWorld Today, "I discovered the homology between the resistance casette and the Vibrio cholerae casette. Then I designed the assay to show they really are casettes." He explained that casettes "are a special genetic structure that allows resistance genes to be exchanged by integrons between strains."

That setup serves many purposes for Vibrio in addition to fending off antibiotics, once they're invented. "One of the main thrusts of our paper," Davies pointed out, "is that this mechanism will pick up any genes; it doesn't have to be just the ones for resistance. So this, we believe, is clearly something that is involved in gene exchange between bacterial species in general.

"In fact," he went on, "there's no reason why the integron-type system would not work in mammalian cells. That's one of the experiments we want to try, because it is a neat way of incorporating genes stably into a new chromosome — say in transgenics."

Davies made the point that "in Gram-negative isolates, such as Escherichia coli, Shigella and Salmonella, the integron system exists, and can pick up seven or eight antibiotic resistance genes at a time. It's also been spotted in a couple of Gram-positive bacteria. This shows that it's a way in which genes can be picked up and passed around."

He pointed to "an interesting problem: that antibiotic resistance genes come from places other than the organism in which we find them now."

The implication of this free-love lifestyle, he went on, "is that within bacteria there is an enormous pool of genes, which can be accessed, probably, by all bacteria. This is being seen in genomics studies, because one finds within different genomes very good similarities between genes from quite different bacteria."

Confronting Free Love Among The Microbes

How can humans cope with this apparently looming phase-out of therapeutic antibiotics?

"We have to learn how to use antibiotics properly," Davies cautioned. "One can certainly remove antibiotic resistance genes from resistance factors," he said. "The integrase would do that; it's reversible. But I think we have to realize that when we use antibiotics, or any agent that acts as a selective force in bacteria, the bacteria survive by being able to pick up the necessary genetic information from this gene supermarket, for which integrons are the shopping baskets."

In their ongoing inquiry into bacterial gene-swapping, Davies and his co-authors "are at the moment looking at the integrases from V. metschnikovii. We would like to define the generality of the system. Find out what some of these open reading frames associated with the integrases actually do.

"We know," he went on, "that some of them determine pathogenicity functions. That's another reason for saying that the integrons can pick up things besides resistance. They can also determine whether an organism becomes virulent."

He continued, "Bacteria have extraordinary genetic flexibility, and have probably always had it. Which is why they've been able to survive on this planet for 3.5 billion years. And during this period, they've almost certainly gone through lots of crises, or minor catastrophes, which they probably solved by genetic methods."

Davies added, "We use all sorts of manipulations in the lab to carry out genetic engineering, while this is the way, par excellence, that bugs do it normally. I think," he concluded, "that maybe we can capitalize on using the bacterial integron-like processes as means of constructing commercially useful strains — in the sense of fixing genes in chromosomes." *

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