A bacterium’s fight against antibiotics seemed to pit each individual prokaryote against the world. If the bacterium had the gene(s) to neutralize the antibiotic, it survived. If it didn’t have those genes, bye-bye bacterium. Whether this bacterium’s neighbor was susceptible or not wasn’t thought to matter.
Research published in today’s Nature shows that antibiotic resistance isn’t so singular. The team led by James Collins found that a single colony of E. coli contains bacteria with differing levels of antibiotic resistance. What’s more, those bacteria that had the stronger resistance seemed to protect the rest of their less resistant colony members from the effects of the antibiotics, even though it came at a cost of fitness to the super-resistant bacteria.
A pure colony of bacteria is essentially a group of clones. In theory, a colony of bacteria is descended from a single bacterium. Because bacteria reproduce by dividing into two identical cells, the colony consists of millions of genetically identical individuals. Mutations can and do occur, and so even bacteria within the same colony can vary slightly. However, two bacteria from Colony A likely have more in common genetically than two bacteria in Colony B. Thus, a “colony” of bacteria could also be conceived of as the equivalent of a family unit.
Collins’ group grew E. coli in a large container called a bioreactor, which allows the researchers to precisely control the bacteria’s environment (and Collins says looks like “a component of a moonshine factory out in the backwoods.” ) They first added the minimum amount of the antibiotic norfloxacin that would inhibit bacterial growth. The researchers took a sample of bacteria every 24 hours, spread the liquid on a petri dish, grew up the bacteria and measured the antibacterial resistance of 12 randomly selected colonies.
Most of the bacterial colonies had lower antibacterial resistance than the entire system grown in the bioreactor. A few colonies, however, had a much higher bacterial resistance than average. These highly resistant bacteria had high levels of the enzyme tryptophanase, which E. coli uses to synthesize indole. A signaling molecule produced during times of high stress, indole can trigger a bacterium to turn on tiny pumps that remove the norfloxacin from within the cell. Indole can also prevent bacteria from being harmed by the high levels of free radicals created during antibiotic treatment.
The highly resistant bacteria synthesized extra indole not for their own benefit, but for the benefit of other colony members. Collins hypothesizes that this is a type of “kin selection,” where an organism acts to protect those who share the same genes, even at high cost to the organism. Because the E. coli in the bioreactor were grown from a single colony, their descendents are essentially one big happy family.
Because so many bacterial species produce indole, Collins thinks that targeting indole signaling might be a new path to create new antibiotics.