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Sleeper cells: the stringent response and persistence in the Borreliella (Borrelia ) burgdorferi enzootic cycle : The stringent response and persistence in B. burgdorferi

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      Most cited references 184

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      The Spandrels of San Marco and the Panglossian Paradigm: A Critique of the Adaptationist Programme

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        Epistasis--the essential role of gene interactions in the structure and evolution of genetic systems.

        Epistasis, or interactions between genes, has long been recognized as fundamentally important to understanding the structure and function of genetic pathways and the evolutionary dynamics of complex genetic systems. With the advent of high-throughput functional genomics and the emergence of systems approaches to biology, as well as a new-found ability to pursue the genetic basis of evolution down to specific molecular changes, there is a renewed appreciation both for the importance of studying gene interactions and for addressing these questions in a unified, quantitative manner.
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          Persister cells.

           Kim Lewis (2009)
          Persisters are dormant variants of regular cells that form stochastically in microbial populations and are highly tolerant to antibiotics. High persister (hip) mutants of Pseudomonas aeruginosa are selected in patients with cystic fibrosis. Similarly, hip mutants of Candida albicans are selected in patients with an oral thrush biofilm. These observations suggest that persisters may be the main culprit responsible for the recalcitrance of chronic infectious disease to antimicrobial therapy. Screening knockout libraries has not produced mutants lacking persisters, indicating that dormancy mechanisms are redundant. Toxin/antitoxin (TA) modules are involved in persister formation in Escherichia coli. The SOS response leads to overexpression of the TisB toxin and persister formation. TisB is a membrane-acting peptide that apparently sends cells into dormancy by decreasing the proton motive force and ATP levels. Stress responses may act as general activators of persister formation. Proteins required for maintaining persisters may represent realistic targets for discovery of drugs capable of effectively treating chronic infections.
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            Author and article information

            Journal
            Environmental Microbiology
            Environmental Microbiology
            Wiley-Blackwell
            14622912
            October 2017
            October 11 2017
            : 19
            : 10
            : 3846-3862
            10.1111/1462-2920.13897
            © 2017

            http://doi.wiley.com/10.1002/tdm_license_1.1

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