Infectious diseases may have an unexpected weakness: their own propensity for laziness.
Researchers genetically engineered "cheating" versions of a common, inflammation-causing microbe. When injected into already-infected mice, the bugs benefited from the chemical labors of other microbes without working themselves.
Able to devote their energies to reproduction, the lazy bugs divided faster than their brethren, and infections turned rapidly less virulent.
"The wild bacteria expend all this energy to make these signaling compounds and virulence factors. That slows down their growth," said Kendra Rumbaugh, a microbiologist at Texas Technical University and lead author of the study, published Thursday in Current Biology. "The cheaters save up like crazy, divide like crazy, and take over the population."
When bacteria invade a host, they exchange chemical signals that activate genes responsible for producing virulence factors — toxic molecules that break down connective tissue, stop cellular defenses and wreak cell-level havoc, creating an environment in which the bacteria can flourish.
Earlier research found that some microbes don't participate in the signaling. Since then, researchers have shown that these freeloaders flourish, at least in laboratory tissue cultures, where they outcompete hard-working bugs and produce less-virulent colonies. Rumbaugh wondered whether the same would happen in an actual infection.
The results, though still preliminary — they involved just one type of infection, observed in a mouse model — suggest that bacterial laziness could be a back-door approach for treating disease, especially drug-resistant strains.
"I like the analogy of cheaters as bacteria who don't pay their taxes," said Rumbaugh. "We all pay taxes, that gets us services and infrastructure. But there's a few people in the population that don't pay, yet they still use these. What happens if cheaters grow to be the majority of the population? Eventually, the society is going to collapse."
To test their hypothesis, Rumbaugh's team engineered a mutant strain of Pseudomonas aeruginosa, a common inflammation-causing bug that infects cuts and open wounds, and is especially troublesome for burn victims and people with AIDS.
Though it usually causes dermatitis, P. aeruginosa can be fatal if infection spreads internally.
The researchers knocked out the genes responsible for signaling, turning their bugs into cheaters. Then they added the mutants to mice with burn wounds infected by normal *P. aeuruginosa. *The engineered strain flourished and soon dominated the bacterial population. More than half of treated mice survived, compared to just one-quarter of an untreated control group.
"These wild bacteria make chemical signals, turning on genes, making proteins, expending energy. There's a significant cost, but a benefit for the whole population," said Rumbaugh. "The cheaters don't make these signals, or all the things controlled by signaling. They just live off what the majority of the population is making."
Rumbaugh hopes the technique could eventually treat infections, especially those resistant to drugs. "We could take an attenuated mutant cheater strain and spike the population," she said. "It would predominate, and maybe make them more susceptible to treatment."
However, she noted that such treatments are still "far off," a caution echoed by Harvard University systems biologist Kevin Foster.
Rumbaugh's laziness hack could work, he said, but several caveats first need to be addressed. "The idea of introducing more bacteria —
even less-virulent ones — to a patient comes with obvious potential side effects, because you have to increase the total number of pathogens in a patient," said Foster, who was not involved in the study.
Other strains of bacteria may also react unpredictably to the mutants. "The modified strain could make things worse," he said.
Citation: "Quorum Sensing and the Social Evolution of Bacterial
Virulence." By Kendra Rumbaugh, Stephen Diggle, Chase Watters, Adin
Ross-Gillespie, Ashleigh Griffin and Stuart West. Current Biology, Vol.
19, Iss. 4, Feb. 19, 2009.
Image: WikiMedia Commons
See Also:
- Gut Bacteria Affect Almost Everything You Do
- A New Weapon in the Battle Against Drug-Tolerant Bacteria
- Bacteria Sacrifice Selves for Greater Good
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