Microbial Warfare

Research Blogging / by Dave Munger /

Antibiotic resistance is more than just a medical scourge; it’s also a window into a war microbes have been waging against each other for hundreds of millions of years.

The 17th-century Dutch scientist Antony van Leeuwenhoek is probably best known for two things: perfecting the microscope and focusing it for the first time on the world of life invisible to the human eye. In reality, he did neither. True compound microscopes had existed for decades before Leeuwenhoek built his devices, and although he created a superior magnifying device, it was not a microscope at all; it was a tiny magnifying glass.

What he saw and recorded through his glass, however, was truly a new world (albeit one that others had seen before him). Leeuwenhoek may have been the first person to observe that tiny “animalcules”—microbes so small that they cannot be seen without magnification—exist in vast numbers and seemingly infinite varieties even in a single drop of pond water.

The field Leeuwenhoek founded, microbiology, is today one of the most fruitful areas of study in all of science. Because microscopic bacteria are responsible for so many diseases that afflict humans, vast resources have been committed to exploring their world—and to developing ways to circumvent their harmful activities.

In 1928, when Alexander Fleming discovered penicillin, the antibiotic produced by the bacteria of genus Penicillium, it seemed that a “miracle cure” for many diseases had been found. But rather than being a mere medical triumph, penicillin’s discovery revealed more of the fundamental complexity to the microbial world. In fact, we now recognize penicillin’s effects as just the latest battle in an evolutionary war that microbes had been waging among themselves for at least hundreds of millions of years.

While it was true that antibiotics like penicillin were effective at treating a variety of diseases caused by bacteria, it was also true that these substances were not effective against all bacteria. Also, bacteria that were not initially resistant to antibiotics were proven capable of developing resistance over time. This was just the beginning. Even now, scientists are still unraveling the many different strategies and tactics bacteria employ in their warfare.

“Lab Rat” is an anonymous biochemistry student who takes time off from lab work to explain what she and her peers are doing at their workbenches and in the field. Last week Lab Rat discussed a 2008 study led by Gautam Dantas at the Washington University School of Medicine, which demonstrated that many naturally occurring microorganisms are already resistant to a wide array of antibiotics. The findings were published in a recent edition of Science.

The researchers took soil samples from “pristine” environments with minimal human presence as well as from urban and agricultural environments. Then, they treated the samples with extremely high concentrations of a variety of antibiotics. In nearly every sample there were many bacteria that were not only resistant to the antibiotics, but could actually consume them as a sole source of food—an indication that the shiny new antibiotics developed in human labs have had natural counterparts in the microbial world for eons. Some of these resistant bacteria were closely related to human pathogens, suggesting that this resistance to antibiotics could be transferred to the microbial species that cause human diseases like strep throat and staph infections, rendering them much more difficult to treat.

Lab Rat points out that bacteria armed with antibiotic weapons can even create collective “hunting parties” to bring down prey. One species, called Myxococcus xanthus, actually hunts in swarms, forming large groups to attack other bacteria and overwhelm their defenses.

Of course, numerical superiority works both ways, such as in the defensive strategy of biofilms, which are protective mats created by communities of bacteria to ward off attack, much the way a group of humans might build a fortress. Biofilms form when bacteria broadcast chemical signals indicating they are willing to help create one. If enough signals are detected, then the multiple different species of bacteria may begin to work together to build a defensive biofilm. But how could such behavior evolve? Wouldn’t it always make more sense to be a “freeloader” and reap the rewards of the other bacteria that are cooperating?

Iddo Friedberg, a microbiologist and music buff at Miami University in Oxford, Ohio, describes a study published this August in PloS One that simulates this scenario. The problem, of course, is that if every bacterium is a freeloader, then the biofilm mat never gets built and none enjoy its protection. To investigate this, Tamás Czárán and Rolf Hoekstra developed a computer model with several different types of freeloaders present. In their model, equilibrium quickly developed between a small number of freeloaders and larger numbers of cooperating bacteria, with teamwork emerging in a variety of environmental conditions. Although there was still some incentive to cheat, it was outweighed by the benefits of cooperation.

Biofilms are one of the ways that human pathogens are able to resist antibiotics, by preventing the chemicals from entering the bacteria in the first place. Friedberg points out that such resistance may be more prevalent than previously imagined: The same team that found antibiotic-eating bacteria in soils has extended their work to humans, discovering that even healthy individuals who had not taken antibiotics for more than a year still hosted benign bacteria with many antibiotic-resistant genes in their stool or saliva.

While the same resistant genes aren’t found in pathogens, it’s certainly possible that these genes could be transferred between bacterial species with devastating results. It appears that, perversely, some of the most virulent bacterial diseases of the past and future may be products of the beneficial domesticated microbial flocks we cultivate within ourselves. The true story of bacterial warfare continues to unfold. As research unveils new connections between microorganisms and human disease, you’ll find expert commentary and analysis of it at ResearchBlogging.org.

Originally published October 7, 2009

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