Abstract
Understanding how antimicrobials act on their target is key for developing new knowledge-based strategies to potentiate antimicrobial efficacy and critical for tackling antimicrobial resistance. Ribosomes are essential for protein synthesis and a major target for antimicrobials. Recently, a bacterial RNA repair system was found to maintain ribosome homeostasis by stabilising the RNA of the small ribosomal subunit and to increase tolerance to ribosome-targeting antimicrobials, representing a previously unrecognised physiological response. The student will now use a combination of molecular biology, biochemistry and single molecule biophysics techniques to mechanistically understand the impact of this system on ribosome function and antimicrobial tolerance.
References
(1) Blanchard et al. (2004) tRNA dynamics on the ribosome during translation. Proc Natl Acad Sci USA 101:12893-12898.
(2) Munro et al. (2010) Spontaneous formation of the unlocked state of the ribosome is a multistep process. Proc Natl Acad Sci USA 107: 709-714.
(3) Perez & Gonzales (2011) In vitro and in vivo single-molecule fluorescence imaging of ribosome-catalyzed protein synthesis. Curr Opin Chem Biol 15: 853-863.
(4) Engl et al. (2016) Cellular and molecular phenotypes depending upon the RNA repair system RtcAB of Escherichia coli. Nucleic Acids Res 44: 9933-9941.
(5) Wang et al. (2011) Mechanistic insights into antibiotic action on the ribosome through single-molecule fluorescence imaging. Ann NY Acad Sci 1241: E1-E16.
(6) Wang et al. (2012) Allosteric control of the ribosome by small-molecule antibiotics. Nat Struct Mol Biol 19: 957-963.
(7) Zhu et al. (2016) Real time determination of bacterial in vivo ribosome translation elongation speed based on LacZα complementation system. Nucleic Acids Res 44: e155.
(8) Scott et al. (2010) Interdependence of cell growth and gene expression: origins and consequences. Science 330: 1099-1102.