Plant metabolite inhibits biofilm formation of bacteria.
Methylerythritol cyclodiphosphate (MEcPP) is an intermediate of the conserved methylerythritol phosphate pathway (MEP), which leads to the biosynthesis of isoprenoids in both plant plastids and bacteria. In plants, MEcPP also acts as a stress signal, especially during oxidative stress. Also in bacteria, MEcPP appears to have a signaling function in stress adaptation. This was recently discovered by scientists at the University of California and partners at the IPB. In the Escherichia coli laboratory strain K12, the scientists could detect increased MEcPP levels after exposing the microorganisms to oxidative stress. As a result, the bacteria produced fewer fimbriae, which are required as adhesive cell extensions for the formation of biofilms. Coli bacteria under oxidative stress therefore form fewer biofilms than under normal conditions.
The Halle partners used limited proteolysis-coupled mass spectrometry (LiP-MS) to demonstrate that MEcPP binds to the histone-like nucleoid structuring protein (H-NS) in E. coli. H-NS is a repressor of the bacterial fimE gene, which in turn negatively regulates fimbriae formation. Binding of MEcPP to H-NS prevents the repression of fimE at the transcript level, resulting in the production of more FimE protein, which consequently switches off fimbriae formation. This signaling cascade therefore leads to the interruption of biofilm formation via reduced fimbriae formation, the research team found.
MEcPP therefore plays a role in both the plant and bacterial stress response. Although bacteria often initiate the formation of biofilms as a protective mechanism against environmental stress, this does not appear to be helpful in the case of oxidative stress. Apparently, bacteria in their life form as individual organisms have better chances of surviving oxidative stress because they can improve their access to antioxidants outside the biofilm network. MEcPP, the scientists conclude, could influence other bacterial H-NS-regulated metabolic pathways as a signaling substance and possibly also modulate the virulence genes of pathogenic E. coli strains, such as the pathogens that cause gastrointestinal and urinary tract infections. Further research should clarify whether other bacterial species, such as staphylococci or streptococci, are also influenced by MEcPP. A better understanding of biofilm formation regulation by MEcPP may be helpful in developing new strategies against chronic infectious diseases or against biofouling on ship hulls.