The Microbes Win

One way scientists look for potential therapeutic drugs is to isolate microbial strains from soils, plants, barks, marine plants and other environmental sources. Researchers isolate bacteria from the mediums then grow the individual strains in special media, ferment then extract the chemicals from the bacteria and test them for biochemical activity. Assays developed for this purpose detect whether the strain produces compounds that could be useful for drug development. Many antibiotics have been developed from screening bacteria and fungi this way and actinomycetes in particular have proven fruitful for drug development. Dozens of different antibiotics, have been developed from actinomycetes especially Streptomyces.

Now scientists at McMaster Universtiy in Ontario have turned these screening experiments around to ask: How many bacterial strains isolated from soil that look like actinomycetes show antibiotic resistance? Many, they found in a study published in Science last week. The scientists isolated 480 morphologically unique spore-forming bacteria, primarily Streptomyces, and tested them for antibiotic resistance against 21 natural and synthetic antibiotics. Every strain was resistant to seven or eight antibiotics - even the newest drugs - and two strains were resistant to 15 types of antibiotics. They found about 200 different antibiotic resistant profiles.

In some ways this is not surprising. Bacteria adapt to prodigiously unfavorable environments and over millions of years have devised a myriad of mechanisms to perfect this adaptation. They disable antibiotics with enzymes, block them from entering their outer membranes, pump them out via efflux mechanisms in their membranes, change the structure of potentially lethal drugs, and muddle the antibiotic target via point mutations. Bacteria like some gram-positive Clostridium and Bacillus species resort to their endospore form in order to survive boiling, complete dessication, high pressure, radiation, acceleration, acidity, and other harsh, abhorrent and seemingly unsurvivable conditions. Gram-negative bacteria often acquire resistance through plasmids that carry antibiotic genes and can be transferred within and across species, as well as perhaps swapped with other plasmids hosted in other bacteria. Actinomycetes are gram-positive, do not form endospores and seem to acquire antibiotic resistance via genomic adaptation, but that hardly limits their antibiotic resistance options.

In the 1970's, scientists did previous work in this area achieved similar results -- if for different ends. Researchers suspected that increased use of antibiotics for disease and agriculture might alter the environment. P Van Dijck and H van de Voorde, for example, tested 29 strains from multiple species across various concentrations of 21 antimicrobial compounds and found that only a small subset of bacteria were sensitive to antibiotics, whereas most showed resistance. Their conclusion? "Spilled antimicrobial agents have little chance of causing an alteration in the microbial ecology. (Applied Environmental Microbiology; March, 1976). While they correctly surmised that microbes had adapted a tremendous capacity to survive, they predicted incorrectly that further antibiotic use would not increase the resistance of populations.

In 1978 researchers tested sludge samples from the notoriously polluted New York Bight. The bacteria populations in the sewage and effluent contaminated water were far more resistant to mercury and certain antibiotics like ampicillin than the control microbial populations.

Bacteria have the advantage of millions of years, so humans have yet to discover many adaptations that bacteria are capable of. We often only notice what scrappy adaptors bacteria are with the demise of something we value, a recreational lake or when they compromise our health. Since only a small percentage of bacteria are pathogenic or wind-up crossing our paths in man-altered ecosystems our knowledge will expand.

All in all, it seems intuitive that soil bacteria which thrive in the company of organisms from which we produce most of our antibiotics, are would be resistant to many antibiotics. The Science authors show the scope of antibiotic resistance in this species and demonstrate the amount of work involved with acquiring this type of information. They confirm that antibiotic resistance mechanisms in natural environments are the same as in clinics. They don't speculate about the overall rate of resistance and interactions between species. Their study suggests that researchers should look more to organisms in the environment for predictions about how antibiotic resistance will evolve in medical settings.

We gain appreciation for natural antibiotic resistance, and can speculate that natural products screening and antibiotic synthesis will yield antibiotics of only limited therapeutic longevity. At the same time, the protection our antibiotics have offered to us so far remains impressive. The Sisyphean challenge of antibiotic resistance is ominous. But while antibiotic resistance may not bode well for humans who spend time in hospitals, the bacteria will continue to thrive on Earth. Despite widespread fretting about the dire straits of the 'planet's' ecosystem, we can be assured that some life will continue to thrive in whatever conditions we leave the planet.


Update: A reader points out that a short overview of this study was aired on NPR. Gerry Wright, the chair of the Department of Biochemistry (and other positions) at McMaster University talked about the study for 7 minutes and 4 seconds on NPR January 20th. Wright says that the study might be useful for scientists developing drugs who could screen new candidates against potential soil resistance. Although this is interesting, some of the drugs trounced by the resistant microbes of the study have actually been highly effective in clinics despite the existence of microbes that resist them. What if they had decided not to develop them based on their suspected susceptibility to resistance?

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