Quorum sensing and lifestyle switching in Yersinia.

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The Yersinia are bacteria which occupy a prominent place in the history of mankind and microbiology. Yersinia pestis, the causative agent of bubonic and pneumonic plague, has claimed millions of lives in periodic pandemics, influencing human history possibly to a greater extent than any other bacterium. The Yersiniae also include species which are pathogenic for animals (farmed and wild), birds and fish. For example, Y. pseudotuberculosis whose lifestyle alternates between the food/water environment and the mammalian gastrointestinal tract, infects livestock as well as captive zoo animals and birds. In humans it causes gastro-intestinal infections and 'far east scarlet-like' fever which involves a severe toxic shock syndrome. Y. pestis evolved from Y. pseudotuberculosis around 20,000 years ago and although these pathogens are >98% identical at the genetic level they cause very different diseases. However the Yersinia species which cause human infections all possess the same pYV extra-chromosomal plasmid which is essential for virulence since it enables Yersinia to subvert its host immune response. As unicellular micro-organisms, the Yersiniae are capable of adapting to diverse environmental stresses (e.g. widely fluctuating temperatures) that facilitate survival in, and migration from, soil and water environments into different hosts (both insects and animals). Although bacteria are single-celled, they can co-ordinate their behaviour by communicating via chemical signal molecules and by forming surface-associated communities known as biofilms. Here, bacteria become enmeshed in a 'slime' layer which confers protection in extreme environments and from the immune system and antibiotics. With respect to Yersinia, bubonic plague is transmitted by fleas whose feeding is blocked by a dense biofilm of Y. pestis in their digestive tracts. Y. pestis also blocks the feeding of the nematode worm, Caenorhabditis elegans, by forming a biofilm around its head. Some Y. pseudotuberculosis strains also readily form biofilms on C. elegans and because it is less dangerous as a pathogen than Y. pestis, it offers a much safer and simpler means of investigating biofilm development on living tissues. This biofilm model is also attractive because it is difficult to study biofilms in the mammalian host. C. elegans shares many genes with humans and so the C. elegans/Yersinia model can be used to identify in vivo genetic features of both the pathogen and the host that contribute to biofilm-mediated interactions which have interesting implications for both the Yersinia/flea and human biofilm-centred infections. We discovered that Y. pseudotuberculosis uses a sophisticated two channel quorum sensing system to make lifestyle decisions according to the prevailing local environmental conditions which help the organism decide whether to build a biofilm, become cytotoxic by secreting Yop proteins or swim away and find a new niche to colonize. This research project aims to gain insight, at the molecular level, into the signalling cascade used by Y. pseudotuberculosis to make these lifestyle decisions including whether to retain the pYV virulence plasmid. We will also seek to gain further insights into the role of the C. elegans host during biofilm formation: the surface ligands to which Yersinia attaches; and, the signalling processes occurring during development of the biofilm. This work will not only inform us about the basic biology of disease causing bacteria but in the longer term may help us to identify novel targets for the prevention or treatment of disease in humans and other animals. This is especially important with respect biofilms which are often the cause of chronic infections. These are very difficult to eradicate and therefore investigating how biofilms develop on living tissues may uncover novel ways for their disruption and prevention.