News Release

Following the path to bacterial virulence

Peer-Reviewed Publication

Instituto Gulbenkian de Ciencia

Infection of An Immune Cell with <i>E. coli</i>

image: A macrophage (in red) is infected with E. coli (dark blue and yellow). view more 

Credit: IGC

This press release is available in Portuguese.

Benign bacteria can evolve and become virulent. That is the case of Escherichia coli (E. coli), which inhabits our gut. Now and then E. coli becomes virulent, inducing disease and even death. How a benign bacterium turns pathogenic has been a puzzle to scientists. In a pioneering study at the Instituto Gulbenkian de Ciência (IGC; Portugal), a research team led by Isabel Gordo, reveals how this can happen. The team followed the evolution of non-pathogenic E. coli in the presence of macrophages (cells of the immune system) and found that they rapidly become pathogenic. In less than 30 days bacteria became more resistant to being killed by the defense cells and acquired the ability to cause death in mice. These findings have implications for the understanding of host-microbe interactions and treatment of bacterial infections. The study was published in the latest issue of the scientific journal PLOS Pathogens*.

Macrophages are a key component of the host defense mechanisms against pathogens. These immune cells act by engulfing and digesting bacteria. Yet, many bacterial species are able to escape the macrophages' action, suggesting that bacteria also have defense mechanisms that evolve when they encounter macrophages.

Isabel Gordo's team followed the evolution of six populations of benign E. coli in Petri dishes, either in the presence or absence of macrophages, for a period of 30 days. After 4 days of evolution (approximately 60 bacterial generations), the researchers observed the appearance of bacterial colonies with different morphologies: either a smaller size or a slime look. However these new colonies were only seen when bacteria grew in the presence of the immune cells. Further experiments showed that these new slime variants could better escape engulfment and death by macrophages than the initial bacteria. Furthermore, the researchers also observed that small colony forming bacteria were more resistant to some antibiotics. Having evolved traits characteristic of those found in pathogens prompted the researchers to test their pathogenic potential in mice. The team observed that mice would survive less to infection caused by E. coli evolved in the presence of macrophage than by E. coli evolved in their absence. These results indicate that the presence of immune cells can rapidly drive bacteria evolution towards pathogenicity.

But what was the mechanism underlying the adaptation of bacteria to the defense cells? And how were these bacteria acquiring traits of pathogenicity so rapidly? By sequencing the genome of evolved bacteria, the researchers found that the acquired virulence was mainly caused by the movement of small DNA fragments (called transposable elements) that can copy themselves into new positions in the genome, thus creating new functions or disabling existing ones.

"We used the power of experimental evolution to directly observe some of the steps E. coli may take in the transition from commensalism to pathogenesis. It was remarkable to observe how rapidly pathogenic traits can evolve. Further studies are required to pinpoint how E. coli adapt to other immune defenses and to open new avenues to the treatment of bacterial infection." – says Isabel Gordo.

###

This study had the collaboration of researchers from the Instituto de Medicina Molecular (IMM; Portugal) and from the Centre for Environmental Biology of the Faculdade de Ciências da Universidade de Lisboa (Portugal). This research was funded by the European Research Council under the European Community's Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no 260421–ECOADAPT) and the Fundação para a Ciência e a Tecnologia (Portugal).

*Miskinyte M, Sousa A, Ramiro RS, de Sousa JAM, Kotlinowski J, Caramalho I, Magalhães S, Soares MP and Gordo I (2013) The Genetic Basis of Escherichia coli Pathoadaptation to Macrophages. PLoS Pathog 9(12): e1003802. doi:10.1371/journal.ppat.1003802 http://dx.plos.org/10.1371/journal.ppat.1003802


Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.