It is postulated that in addition to cell density, other factors such as the dimensions and diffusional characteristics of the environment could influence quorum sensing (QS) and induction of genetic reprogramming. Modeling studies predict that QS may operate at the level of a single cell, but, owing to experimental challenges, the potential benefits of QS by individual cells remain virtually unexplored. Here we report a physical system that mimics isolation of a bacterium, such as within an endosome or phagosome during infection, and maintains cell viability under conditions of complete chemical and physical isolation. For Staphylococcus aureus, we show that quorum sensing and genetic reprogramming can occur in a single isolated organism. Quorum sensing allows S. aureus to sense confinement and to activate virulence and metabolic pathways needed for survival. To demonstrate the benefit of confinement-induced quorum sensing to individuals, we showed that quorum-sensing bacteria have significantly greater viability over non-QS bacteria.
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E.C.C. was supported by US Air Force Office of Scientific Research (AFOSR) grant FA 9550-07-1-0054 and US National Science Foundation Integrative Graduate Education and Research Traineeship Fellowship grant DGE-0504276. D.M.L. was supported by AFOSR grant FA 9550-07-1-0054 and Defense Threat Reduction Agency grant B0844671. N.P.D., A.C. and G.S.T. were supported by US National Institutes of Health (NIH) grants AI-037142 and AI-047441. H.G. was supported by NIH grant R01 AI-064926. C. J. B. was supported by the U.S. Department of Energy, Office of Basic Energy Sciences, Division of Materials Sciences and Engineering and Sandia National Laboratories’ Laboratory Directed Research and Development program. Further support was provided by the NIH/Roadmap for Medical Research grant PHS 2 PN2 EY016570B. The authors also acknowledge L. Kenney and M. Federle for useful comments. Some images in this paper were generated in the University of New Mexico Cancer Center Fluorescence Microscopy Facility, supported as detailed at http://hsc.unm.edu/crtc/microscopy/Facility.html. Sandia is a multiprogram laboratory operated by Sandia Corporation, a Lockheed Martin Company, for the US Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.
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Nature Reviews Drug Discovery (2017)