Rapid translational responses as a novel mechanism to repair cellular damage caused by the bacterial injectisome in animal and plant host cells

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When animal and plant cells are assaulted by microbes, this causes changes in the production of proteins by the attacked cells. Proteins are large biological molecules with many different functions that include, among other things, structural proteins, signal molecules (including hormones), enzymes that catalyse specific chemical reactions, immune factors (including antibodies), and 'transcription factors'. Transcription factors control access to protein-making instructions archived in a cell's DNA by switching on synthesis of specific 'messenger RNA' molecules that transport copies of these instructions to 'polysomes'. Polysomes contain the complex machinery that 'translates' the data contained in each messenger RNA to guide assembly of a specific protein.Projecting from the surfaces of many disease-causing bacteria are tiny needle-like structures called 'injectisomes'. Injectisomes are nano-syringes that inject substances called 'effectors' into host cells to promote disease by, for example, inhibiting resistance. Injectisomes are used not only by bacteria that attack animals and humans, but also by bacteria that attack plants, as well as by food poisoning bacteria that colonise the edible parts of plants. Thus, understanding how cells respond to penetration by injectisomes is important for development of improved medical treatments, for enhancing protection of crops against bacterial diseases, and increasing food safety. Macrophages are white blood cells that attack invading microbes. The project leader discovered that when macrophages are penetrated by the injectisomes of attacking Salmonella bacteria, the host cell polysomes selectively increase synthesis of specific transcription factors, which in turn changes the pattern of copying of messenger RNAs from the macrophage's DNA. This reprogramming of protein synthesis activity (translation) by polysomes is remarkably rapid, occurring within seconds to minutes of penetration, and its discovery raises important new questions about how host cells respond to bacterial attack.The key questions we will answer are: - Are the polysomes of host cells responding to the effectors injected by the bacteria or to the shock of penetration? - Plant-attacking bacteria also use injectisomes are part of their armoury, so does the rapid change in polysome activity also occur when plant cells are attacked, either by bacteria that cause disease in plants, or by food poisoning bacteria that colonise plants?- How similar are the responses to bacterial and plant cells and can we separate the responses caused by the shock of penetration versus those caused by the effectors?- Is the rapid change in polysome activity an early step in mounting resistance to bacterial attack and repair of the cell, or does it mark a stage in the destruction of the host cell?