Bacterial charity work leads to population-wide resistance

Can bacteria employ a population based resistance mechanism to counter drugs?

A study published in Nature, Sept. 2010 suggests this is likely.

Lee et al. show that when a population of E. coli cells was evolved in the presence of norfloxacin, it developed resistance, the level of which was not explained by the resistance of its individual components. That is, this evolved resistant population was composed of a larger proportion of cells that were less resistant to the antibiotic and a smaller proportion that had greater resistance. Their speculation that the high resistant isolates were generating benefits for the low resistant ones led them to find that indole, secreted by the resistant cells was the mediator.

The high resistant isolates had mutations that conferred drug resistance, but were unrelated to indole production. It seems that because these cells are resistant they can produce indole in the presence of antibiotic while the others are inhibited. Furthermore if the gene producing indole is deleted from the high resistant isolate, it can grow better in the presence of antibiotic suggesting that indole production has costs associated with it. But a mixed population with less highly resistant cells and a higher proportion of less resistant cells, could grow in the presence of norfloxacin to substantial levels, only if the highly resistant cells were capable of producing indole. Indole seems to enable antibiotic detoxification in the less resistant isolates by up-regulating export pathways and oxidative stress protective mechanisms.

Hence, the altruistic production of indole by the high resistant isolate enables the population as a whole to grow in the presence of otherwise inhibitory concentration of norfloxacin.

The authors suggest that:

This altruism allows weaker constituents to survive and concurrently explore the space of beneficial mutations, a phenomenon similar in character to kin selection. These few drug-resistant mutants, by enhancing the survival capacity of the overall population in stressful environments, may also help to preserve the potential for the population to return to its genetic origins should the stress prove transient.

What’s more, probing into ways in which a population reacts to the presence of antibacterial substances to gain resistance will help develop means to intervene this phenomenon.