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Worms strike see-saw balance in disease resistance

3 March 2011

New research, funded by BBSRC has shown that nematode worms have to trade-off resistance to different diseases, gaining resistance to one microbe at the expense of becoming more vulnerable to another. This finding, published in PLoS ONE today (2 March 2011), reveals that the worms, called C. elegans, have a much more complex immune system than was previously thought and shows how important such trade-offs are across the animal kingdom.

nematode worm C. elegans. © Robin May, University of Birmingham

The nematode worm C. elegans
© Robin May, University of Birmingham

Dr Robin May from the University of Birmingham's School of Biosciences who worked on the study explains: "This finding was a real surprise. These worms have quite a simple immune system, so when we deleted a gene which we already knew provided resistance to a type of fungus; we were amazed to find that the worms became more resistant to Salmonella bacteria. It seems that evolving resistance to the fungus came at the cost of making the worms more vulnerable to other diseases.

"Whilst scientists have seen this phenomenon, where there is a see-saw balance between immunity to different diseases, in more complex animals before, it has never been shown in anything as simple as a nematode worm. We think that this phenomenon evolved separately in C. elegans indicating that this trade off is important across the animal kingdom."

An immune system costs an animal a lot of energy to maintain and carries the risk of inadvertently damaging the host, as in the case of allergies. Because of this, animals have to balance the costs and benefits of immunity, so putting more resources into fighting off bacteria might increase susceptibility to viruses for example, or vice versa.

Dr May continues: "All animals live in a world of limited resources which means that evolution has to compromise. Being a successful animal means that evolution has struck the right balance. It seems in this instance it was important that these nematodes became resistant to fungi like Cryptococcus even if it cost them resistance to Salmonella."

Fluorescence image of the nematode worm C. elegans infected with Salmonella bacteria. © Robin May, University of Birmingham

Fluorescence image of the nematode worm C. elegans infected with Salmonella bacteria
© Robin May, University of Birmingham

The gene that the researchers deleted, lys-7, normally produces something called a lysozyme which works in the immune system to attack invading microbes. Although most lysozymes fend off bacterial infections, this particular version seems to protect against infection by a type of fungus called Cryptococcus neoformans which is also a pathogen of humans causing infections in people with weakened immune systems like AIDS patients.

Dr May continues: "We're not quite sure why losing this lysozyme makes the worms better equipped to fight off Salmonella. One possibility is that losing the gene gives other parts of immune system a boost, or perhaps Salmonella normally turns on its defence mechanisms in response to the presence of this lysozyme."

Professor Douglas Kell, BBSRC Chief Executive said "Work in simple model organisms can provide us with insights into fundamental biology that apply across the natural world. This research is a great example. Understanding how the immune system works and how it has evolved in different animals will be important in dealing with a number challenges facing society, from chronic inflammation reducing people's quality of life in old age, to crop pests developing resistance to pesticides."

This research was also supported by a Medical Research Council studentship.

ENDS

Notes to editors

The research is described in the following journal paper: Marsh EK, van den Berg MCW, May RC (2011) A Two-Gene Balance Regulates Salmonella Typhimurium Tolerance in the Nematode Caenorhabditis elegans. PLoS ONE 6(3): e16839. doi:10.1371/journal.pone.0016839 http://dx.plos.org/10.1371/journal.pone.0016839.

About BBSRC

BBSRC is the UK funding agency for research in the life sciences. Sponsored by Government, BBSRC annually invests around £470M in a wide range of research that makes a significant contribution to the quality of life in the UK and beyond and supports a number of important industrial stakeholders, including the agriculture, food, chemical, healthcare and pharmaceutical sectors.

BBSRC provides institute strategic research grants to the following:

  • The Babraham Institute
  • Institute for Animal Health
  • Institute of Biological, Environmental and Rural Sciences (Aberystwyth University)
  • Institute of Food Research
  • John Innes Centre
  • The Genome Analysis Centre
  • The Roslin Institute (University of Edinburgh)
  • Rothamsted Research

The Institutes conduct long-term, mission-oriented research using specialist facilities. They have strong interactions with industry, Government departments and other end-users of their research.