Gain an understanding of bacterial manipulation of apoptotic pathways, including both the induction and inhibition of apoptosis.
Bacteria can manipulate apoptotic pathways either through their induction or their inhibition during infection. Interestingly bacterial species that are closely related through evolution can have diverse effects on apoptosis with some inducing its activation and others causing its delay with few indicators as to why there is such a diverse response. The purpose of apoptosis manipulation can for the most part only be speculated on but it seems most likely that inhibition of these pathways in infected cells aids in securing the replication niche for pathogens. In contrast their induction may either aid in bacterial spread from infected host cells or alternatively from the host perspective, induction of apoptosis may aid in the anti-bacterial response by removing infected cells.
Effector proteins from Salmonella Typhimurium can interact with apoptotic enzymes such as the caspases causing their activation resulting in a unique situation where the host cell can inadvertently aid infection. These enzymes go on to then cleave bacterial proteins into subunits within the infected cell allowing these subunits to travel to different parts of the cell to carry out their function (Srikanth* and Wall* et al., 2011).
Editor’s comments on peer reviewed articles:
- Salmonella gets help from host. Nature – Research Highlights (2010). 467:887
- http://www.nature.com/nature/journal/v467/n7318//full/467887e.html
- Salmonella stealth bomber. Science –Editor’s Choice (2010). 330:292
Salmonella Typhimurium is not unique in its ability to interact with Programmed Cell Death (PCD) pathways such as apoptosis. There are many possible outcomes upon bacterial infection, each potentially minimising or exacerbating the inflammatory response by the immune system. Through the study of these outcomes of PCD we hope to better understand the delicate balance between the induction of inflammatory or non-inflammatory responses by host cells in response to microbial pathogens (Fig 2).
As well as potentially activating PCD pathways microbial pathogens can also inhibit their progress. In our laboratory we study in particular the activation and inhibition of the PCD pathway apoptosis by bacterial pathogens. We do this with respect to a number of pathogenic enteric bacteria although many more are known to interact with a variety of apoptotic proteins as is shown in Fig 3.
The consequences of host apoptosis being inhibited are numerous but in the context of microbial disease the immediate effect of immune cells persisting is a potential for increased and prolonged inflammation. With recent studies implicating bacterial pathogens in driving intestinal inflammation in diseases such as Inflammatory Bowel Disease (IBD) this is of particular interest to us.
Collaborators:
Professor Beth A. McCormick, University of Massachusetts Medical School, Worcester, USA
Dr. Daniel Walker, Dr. Simon Milling, Dr. Richard Burchmore, University of Glasgow