Nice Germs Finish Last

Resistant Bacteria Help Their Kin

Good Samaritans are in our own bodies. James J. Collins, a biologist at Boston University, has found small numbers of drug-resistant bacteria help their vulnerable counterparts survive antibiotic onslaughts, even at their own peril.

Even bacteria occasionally take one for the team. The bugs typically develop drug resistance by acquiring genetic mutations that fend off antibiotics; eventually the survivors and their offspring take over the colony, and the drugs stop working altogether. A new study suggests that resistance can spread in an entirely different way—through altruism. Collins and his colleagues exposed one culture an E- coli colony of with a non-lethal dose of antibiotics. Not surprisingly a few cells carried mutations that allowed them to survive. Rather than taking over the colony, these mutant cells began secreting a molecule called indole, which turns on pumps that push drugs out of the cell. The mutants did not need to produce indole to survive. They were simply working for the greater good.

Altruists at a Cost

The indole production came at a cost to the resistant bacteria. Since they spent energy making the indole, they had fewer resources to use for their own growth and reproduction and grew more slowly than mutants that didn’t produce indole. Somewhat similar to the evolutionary idea of kin selection, the process may ensure survival of the mutants’ relatives.

The findings could spur scientists to develop better antibiotics. If indole allows pathogenic bacteria to withstand antibiotics, it may be possible to thwart drug resistance by blocking indole signaling with small molecules.

Collins notes, “These unicellular organisms can function as a multicellular organism of sorts, thus isolating samples may not be representative of the big picture.

The new findings shed light on the level of complexity and heterogeneity within bacterial strains. Until now, it was assumed that the overall resistance level of any given population was reflected in each of its isolates. Instead, Collins and his team found that dramatic differences can exist within a single population with some bacteria showing exceptional resistance and some almost none, not unlike cancer cells in humans.

The fact that the full complexity of bacteria strains can now be more accurately understood has significant ramifications for the medical community. "Now, when we measure the resistance in a population, we'll know that it may be tricking us," said Collins. "We'll know that even an isolate that shows no resistance can put up a stronger battle against antibiotics thanks to its buddies."

Saeed Tavazoie, a molecular biologist who conducted a study along with graduate student Ilias Tagkopoulos and post-doctoral researcher Yir-Chung Liu, explains, "What we have found is the first evidence that bacteria can use sensed cues from their environment to infer future events."

Doctors May Want to Revise Their Strategies

Doctors may one day want to revise their strategy for avoiding antibiotic resistance in people, perhaps by varying the number of pills taken every day to make it harder for resistance to develop in bacteria.

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