SystemsX.ch

Exploring response surfaces and synergistic interactions of antibiotic combination treatment for Neisseria gonorrhoeae

IPhD grant from SystemsX.ch (The Swiss Initiative in Systems Biology)

Start/End: 01.01.2014 – 31.12.2016
Approved amount: 194’000 CHF (~ 211k USD)
Applicant(s): Christian L. Althaus, Lucy J. Hathaway, Nicola Low

Pharmacodynamic functions for different antimicrobials in a gonorrhoea reference strain (from ref. 1).

Pharmacodynamic functions for different antimicrobials in a gonorrhoea reference strain.(from ref. 2).

In this IPhD project, we will adopt a systems biology approach to explore the impact of antibiotic combination regimens on the in vitro growth kinetics of N. gonorrhoeae. First, we will investigate whether there are fundamental differences between the mechanisms at which different antibiotics interfere with bacterial growth using so-called pharmacodynamic functions. In a second step, we will develop a mathematical model to predict the effect of combination antibiotic regimens on the growth of N. gonorrhoeae. Lastly, we will explore potential synergistic or antagonistic interactions between antibiotics that could be considered for optimized treatment protocols for gonorrhoea.

Publications
  1. Foerster S, Golparian D, Jacobsson S, Hathaway LJ, Low N, Shafer WM, Althaus CL, Unemo M. (2015) Genetic resistance determinants, in vitro time-kill curve analysis and pharmacodynamic functions for the novel topoisomerase II inhibitor ETX0914 (AZD0914) in Neisseria gonorrhoeae. Front Microbiol, 6:1377.
  2. Foerster S, Unemo M, Hathaway LJ, Low N, Althaus CL. (2016) Time-kill curve analysis and pharmacodynamic modelling for in vitro evaluation of antimicrobials against Neisseria gonorrhoeae. BMC Microbiol, 16:216.
  3. Foerster S, Desilvestro V, Hathaway LJ, Althaus CL, Unemo M. (2017) A new rapid resazurin-based microdilution assay for antimicrobial susceptibility testing of Neisseria gonorrhoeae. J Antimicrob Chemother.