Antibacterial Potential of RNA G-quadraplexes (360G-Wellcome-211599_Z_18_Z)

RNA G-quadruplexes (RG4s) are stable RNA molecules which have a unique, four-stranded structure that contain two or more layers of G-quartets. E. coli, along with other bacteria types have undergone an evolutionary depletion of RG4-forming sequences. This may likely be a result from the ability of these quadruplexes to impair translation and growth in these bacteria. The canonical structure of RG4s is as follows: (G)3-(N)1-7-(G)3-(N)1-7-(G)3-(N)1-7-(G)3-(N)1-7. This project will explore the antibacterial potential of two novel RG4s (G3A2 and G3U) against three bacterial isolates: E.coli, MSSA, and MRSA. Microtitre assays will be performed to determine the bacteriostatic or bactericidal effects of these RG4s. A control RNA that does not form a G-quadruplex will be used as a control. Minimal inhibitory concentrations (MICs) of these RG4s will be determined and they will be compared to that of currently used antibiotics (i.e. 3rd generation cephalosporins, flucoxacillin and daptamycin, respectively). The ability of heat- and salt-shock to enhance the natural competence of the RNA G-quadruplexes will also be evaluated. Key goals: This project will give rise to new information on the antibacterial potential of RNA G-quadruplexes and it will also bring forward new challenges directed towards their pharmaceutical application and future development.