Abstract For more than four thousand years technological advances have enabled us to see the invisible through the invention and development of microscopes that have delivered magnification alongside resolution. Over the same timescale this has led to the discovery of microscopic organisms and the birth of the science of microbiology. From ancient theories that an invisible life form existed light microscopy established their presence in the 1600s. Over the next couple of centuries light microscopes were developed with improved illumination and precision as microbiologists created ways to grow and sample their microbes. In so doing microscopy and microbiology extended our understanding of infection transmission from generalised miasma and germ theories to linking specific diseases with particular microbes to make diagnosis and prevention more reliable. Electron and fluorescent microscopy provided step changes in the visualisation of the finer detail of microbes, enabling the characterisation of internal structures and the unravelling of the molecular mechanisms of biological processes. We are now within an era of imaging microbes in three dimensions over time with sensitivity and super resolution to study the microbes in their natural habitat such as within infected tissues. With the advent of multi-modal, correlative and molecular imaging the future holds the promise of a full interrogation of the internal machineries of microbes and real-time tracking of their lifecycle and interactions. This will help deliver the next generation of antibiotics and alternative prevention strategies to enable everyone to live longer, healthier lives.
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