Nature. Bacterial charity work leads to population-wide resistance

[Giuseppe]

Bacterial charity work leads to population-wide resistance (Nature, letter, extracts, edited)


[Source: Nature, extracts: <cite cite="http://www.nature.com/nature/journal/v467/n7311/full/nature09354.html">Access : Bacterial charity work leads to population-wide resistance : Nature</cite>. Edited.]

Letter

Nature 467, 82-85 (2 September 2010) | doi:10.1038/nature09354; Received 6 April 2010; Accepted 14 July 2010

Bacterial charity work leads to population-wide resistance

Henry H. Lee 1,2, Michael N. Molla 1,2, Charles R. Cantor 2 & James J. Collins 1,2,3
1. Howard Hughes Medical Institute, Center for BioDynamics, Boston, Massachusetts 02115, USA
2. Center for Advanced Biotechnology, Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, USA
3. Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts 02215, USA

Correspondence to: James J. Collins 1,2,3 Email: jcollins@bu.edu


Abstract

Bacteria show remarkable adaptability in the face of antibiotic therapeutics. Resistance alleles in drug target-specific sites and general stress responses have been identified in individual end-point isolates1, 2, 3, 4, 5, 6, 7. Less is known, however, about the population dynamics during the development of antibiotic-resistant strains. Here we follow a continuous culture of Escherichia coli facing increasing levels of antibiotic and show that the vast majority of isolates are less resistant than the population as a whole. We find that the few highly resistant mutants improve the survival of the population’s less resistant constituents, in part by producing indole, a signalling molecule generated by actively growing, unstressed cells8. We show, through transcriptional profiling, that indole serves to turn on drug efflux pumps and oxidative-stress protective mechanisms. The indole production comes at a fitness cost to the highly resistant isolates, and whole-genome sequencing reveals that this bacterial altruism is made possible by drug-resistance mutations unrelated to indole production. This work establishes a population-based resistance mechanism constituting a form of kin selection9 whereby a small number of resistant mutants can, at some cost to themselves, provide protection to other, more vulnerable, cells, enhancing the survival capacity of the overall population in stressful environments.


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[Gert van der Hoek]

Re: Nature. Bacterial charity work leads to population-wide resistance

September 1, 2010 |

A Few Drug-Resistant Bacteria May Keep the Whole Colony Alive

Drug-resistant mutant bacteria produce compounds called indoles that can protect large numbers of nonresistant colony mates. New treatment strategies should follow.

There’s been an unexpected development in our understanding of drug resistance in bacteria. The accepted scenario was a simple case of evolutionary selection. In a bacterial population exposed to a killer drug, a few lucky individuals might have a genetic mutation that kept them alive. They survived to reproduce, while the rest of the population perished. In short order, the entire colony consisted only of the offspring of the drug-resistant founders.

But a new study finds that just a few resistant mutants can protect large numbers of normal bacteria that would have been thought to be susceptible to the drug therapy. The research appears in the journal Nature. (See previous post,ed)

The key seems to be that the drug-resistant mutants produce large amounts of compounds called indoles, which help bacteria tough out tough times. And the indoles from the mutants buck up the regular, nonresistant bacteria. The mutants themselves seem to be acting altruistically—their own growth is slowed by their indole production.

The finding should lead to new strategies to fight drug resistance. And it could also improve our take on evolutionary dynamics, in systems that apparently experience selection pressure at both the individual and group levels.

Steve Mirsky