In many biological examples of cooperation, individuals that cooperate cannot benefit from the resulting public good. This is especially clear in cases of self-destructive cooperation, where individuals die when helping others. If self-destructive cooperation is genetically encoded, these genes can only be maintained if they are expressed by just a fraction of their carriers, whereas the other fraction benefits from the public good. One mechanism that can mediate this differentiation into two phenotypically different sub-populations is phenotypic noise1, 2. Here we show that noisy expression of self-destructive cooperation can evolve if individuals that have a higher probability for self-destruction have, on average, access to larger public goods. This situation, which we refer to as assortment, can arise if the environment is spatially structured. These results provide a new perspective on the significance of phenotypic noise in bacterial pathogenesis: it might promote the formation of cooperative sub-populations that die while preparing the ground for a successful infection. We show experimentally that this model captures essential features of Salmonella typhimurium pathogenesis. We conclude that noisily expressed self-destructive cooperative actions can evolve under conditions of assortment, that self-destructive cooperation is a plausible biological function of phenotypic noise, and that self-destructive cooperation mediated by phenotypic noise could be important in bacterial pathogenesis.

Suicidal Salmonella sacrifice themselves to allow their clones to get a foothold in the gut. Bacteria can commit suicide to help their brethren establish more damaging infections — and scientists think that they can explain how this behaviour evolved. The phenomenon, called self-destructive cooperation, can help bacteria such as Salmonella typhimurium and Clostridium difficile to establish a stronghold in the gut. By studying mice infected with S. typhimurium, researchers from Switzerland and Canada have now demonstrated how this 'kamikaze' behaviour arose. The team, led by Martin Ackermann of ETH Zurich in Switzerland, studied how S. typhimurium expresses the Type III secretion systems virulence factors (TTSS-1) that inflame the gut. This eradicates intestinal microflora that would otherwise compete for resources — but also kills most of the S. typhimurium cells in the vicinity. After this assault, the way is clear for remaining S. typhimurium to take advantage and further colonise the gut. But in the middle of the gut cavity, or lumen, only about 15% of the S. typhimurium population actually expresses TTSS-1. In contrast, in the tissue of the gut wall, almost all bacteria express TTSS-1. As more bacteria invade the tissue, gut inflammation increases and kills off the invaders (especially those within the tissue) - along with the other competing gut flora.

Humans are colonized by multitudes of commensal organisms representing members of five of the six kingdoms of life; however, our gastrointestinal tract provides residence to both beneficial and potentially pathogenic microorganisms. Imbalances in the composition of the bacterial microbiota, known as dysbiosis, are postulated to be a major factor in human disorders such as inflammatory bowel disease. We report here that the prominent human symbiont Bacteroides fragilis protects animals from experimental colitis induced by Helicobacter hepaticus, a commensal bacterium with pathogenic potential. This beneficial activity requires a single microbial molecule (polysaccharide A, PSA). In animals harbouring B. fragilis not expressing PSA, H. hepaticus colonization leads to disease and pro-inflammatory cytokine production in colonic tissues. Purified PSA administered to animals is required to suppress pro-inflammatory interleukin-17 production by intestinal immune cells and also inhibits in vitro reactions in cell cultures. Furthermore, PSA protects from inflammatory disease through a functional requirement for interleukin-10-producing CD4+ T cells. These results show that molecules of the bacterial microbiota can mediate the critical balance between health and disease. Harnessing the immunomodulatory capacity of symbiosis factors such as PSA might potentially provide therapeutics for human inflammatory disorders on the basis of entirely novel biological principles.

In general, people coexist peacefully with the innumerable microorganisms that colonize the gut. Some gut microbes, however, are potential pathogens; moreover, inappropriate immune responses directed against gastrointestinal flora may be involved in the pathogenesis of inflammatory bowel diseases (IBDs) such as ulcerative colitis. Mazmanian et al. used a mouse model of IBD in which naïve effector T cells were introduced into immunodeficient mice, along with the bacterium Helicobacter hepaticus, to investigate the hypothesis that IBDs may involve an imbalance between potentially harmful and potentially beneficial commensal bacteria. Co-colonization with the bacterium Bacteroides fragilis protected these mice from colitis, whereas B. fragilis lacking the surface polysaccharide PSA (B. fragilis {Delta}PSA) were not protective. Colon cultures revealed increased abundance of pro-inflammatory cytokines like tumor necrosis factor-{alpha} (TNF-{alpha}) in mice with experimental colitis, an increase blocked by colonization with B. fragilis but not B. fragilis {Delta}PSA. Oral PSA protected against this model of colitis as well--and also against a chemically induced model of colitis. PSA increased expression of the transcript encoding the anti-inflammatory cytokine interleukin-10 (IL-10) in mouse colon and also in cocultures of bone marrow-derived dendritic cells and naïve CD4+ T cells (BMDC-T cell cocultures). PSA decreased production of TNF-{alpha} in BMDC-T cell cocultures infected with H. hepaticus, an effect blocked by neutralizing antibodies directed against the IL-10 receptor. Furthermore, such antibodies inhibited the protective effect of PSA in the T cell-transfer model of colitis, and PSA failed to protect against colitis when the naïve effector T cells were derived from mice lacking IL-10. The authors thus conclude that B. fragilis PSA can modulate the inflammatory response associated with H. hepaticus and thereby protect against IBD. Kullberg discusses the results and provides thoughtful commentary.

The number of people hospitalized with a dangerous intestinal superbug has been growing by more than 10,000 cases a year, according to a new study. The germ, resistant to some antibiotics, has become a regular menace in hospitals and nursing homes. The study found it played a role in nearly 300,000 hospitalizations in 2005, more than double the number in 2000. The infection, Clostridium difficile, is found in the colon and can cause diarrhea and a more serious intestinal condition known as colitis. It is spread by spores in feces. But the spores are difficult to kill with most conventional household cleaners or antibacterial soap.

Symbiotic mutualism with gut microbes occurs in all metazoans, and it is well established that commensal bacteria influence multiple aspects of host gut physiology such as innate immunity and development. However, our understanding of these coevolved interactions between prokaryotes and eukaryotes remains unclear. One mechanism by which commensal bacteria modulate host intracellular signaling pathways in order to avoid excess inflammation has now been determined. In this process, bacterial-induced reactive oxygen species in gut epithelial cells act as key messengers that inhibit the cullin-1–dependent protein degradation machinery, which in turn results in the stabilization of a master negative regulator of inflammation, inhibitor of nuclear factor-{kappa}B (I{kappa}B). Furthermore, this bacterial-mediated system also appears to be involved in the stabilization of a key developmental regulator, β-catenin. These findings provide new insights into the molecular mechanisms by which commensal microbes shape host cellular physiology.