Biofilms Use Chemical Weapons

ViolaceinFew bacteria are loners – more often they grow in crowds and squat on surfaces where they form a community. These so-called biofilms develop on any surface that bacteria can attach themselves to. The dilemma we face is that neither disinfectants and antibiotics, nor phagocytes (cells which typically destroy microorganisms) and our immune system can destroy these biofilms. This is a particular problem in hospitals if these bacteria form a community on a catheter or implant where they could potentially cause a serious infection. Scientists in Germany have just identified one of the fundamental mechanisms used by the bacteria in biofilms to protect themselves against the attacking phagocytes – the discovery that biofilm bacteria use chemical weapons to defend themselves.

Until now, scientists have been unable to understand the root of the biofilm problem – the inability of phagocytes to destroy these biofilms. The researchers investigated this problem by modelling the problem on marine bacteria. Marine bacteria face constant threats in their habitat from environmental phagocytes (amoebae) which behave in a similar way in the sea as do immune cells in our body (i.e. they seek out, and feed on, bacteria). As long as bacteria are swimming freely and separately in the water, they are easy pickings for these predators. However, if they become attached to a surface and socialize with other bacteria, the amoebae can no longer successfully attack them. The surprising thing was that the amoebae attacking the biofilms were de-activated or even killed. The bacteria are clearly not just building a fortress, they are also fighting back. The bacteria utilise chemical weapons to achieve this. A widespread and highly effective molecule used by marine bacteria is the pigment violacein. Once the defence system is ready, the biofilm shimmers a soft purple colour. If the attackers consume just a single cell of the biofilm – and the pigment they contain – this paralyses the attackers momentarily and the violacein triggers a suicide mechanism in the amoebae. Biofilms may no longer be seen just as a problem; they may also be a source of new bioactive agents. When organized in biofilms, bacteria produce highly effective substances which individual bacteria alone cannot produce. And the scientists hope to use these molecules to combat a specific group of pathogens, human parasites that cause devastating infections such as sleeping illness and malaria. Amoeba are ancient relatives of these pathogens and thus biofilm-derived weapons may provide an excellent basis for the design of new parasiticidal drugs.

Marine Biofilm Bacteria Evade Eukaryotic Predation by Targeted Chemical Defense. 2008 PLoS ONE 3(7): e2744
Many plants and animals are defended from predation or herbivory by inhibitory secondary metabolites, which in the marine environment are very common among sessile organisms. Among bacteria, where there is the greatest metabolic potential, little is known about chemical defenses against bacterivorous consumers. An emerging hypothesis is that sessile bacterial communities organized as biofilms serve as bacterial refuge from predation. By testing growth and survival of two common bacterivorous nanoflagellates, we find evidence that chemically mediated resistance against protozoan predators is common among biofilm populations in a diverse set of marine bacteria. Using bioassay-guided chemical and genetic analysis, we identified one of the most effective antiprotozoal compounds as violacein, an alkaloid that we demonstrate is produced predominately within biofilm cells. Nanomolar concentrations of violacein inhibit protozoan feeding by inducing a conserved eukaryotic cell death program. Such biofilm-specific chemical defenses could contribute to the successful persistence of biofilm bacteria in various environments and provide the ecological and evolutionary context for a number of eukaryote-targeting bacterial metabolites.

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