Bacteria are smart and tenacious little critters. They grow in any hospitable place, including the nutritious environs of a human body. When we protest their presence by taking medicine, they reveal their brilliance by coming up with every imaginable way to resist the medication.
The problem of drug resistance is one of the pre-eminent challenges facing medicinal chemists. We are fast at making new drugs, but microbes are equally fast in circumventing their action. Bacteria come up with molecular strategies to resist therapeutic agents, and then they share the strategies with other bacteria by transferring drug resistance genes from one to another.
The public-health challenge is so intractable that some experts believe we face a future where antibacterials are simply ineffective because of widespread drug resistance. Just like 100 years ago when there were no useful drugs and infectious diseases were truly scary.
And now, with a new publication from Boston University and Harvard, the problem seems at once to be even more difficult while also opening a new line of attack (Nature 467 [September 2, 2010], 82–85).
Existing dogma says that when a population of bacteria is exposed to a drug intended to kill cells, most of the cells cooperate and die. However, in a large population there will generally be a few cells harboring a mutation that makes the cell less susceptible to the bacteriocidal drug. Thus, sensitive cells die out only to be replaced by regrowth of the few remaining resistant ones.
The new work shows the situation to be more complex. When a population of bacteria is exposed, the few cells that are resistant secrete a substance that helps the sensitive ones survive as well. Thus, the individual cells act in the interest of the group to ensure survival.
This finding complicates disease treatment but raises the possibility that the secreted substance may itself be a target for therapeutic intervention. Since this is revealed to be a small molecule (indole), industrious chemists are likely already at work conceiving a new generation of ways to combat infections.