Assay development and efficacy testing of novel and established antimicrobials

Over the past 25 years, new antimicrobial discovery has ground to a halt, this combined

with a rise in antimicrobial resistance in pathogenic bacteria, is causing the number of

effective treatments available to humankind decrease.

For my thesis, I explored the testing methods for screening antimicrobial compounds and

found them to be inefficient. One of the limiting factors for the discovery of new antimicrobial

compounds are the efficacy testing assays and high-throughput screening methods used

by researchers. These methods mainly measure the ability of a compound to diffuse

through or across a medium, be it agar, filter papers or testing strips.

Within this thesis I developed new testing assays for a family of novel antimicrobials, as

their efficacy wasn't measurable by the standard procedures. I also measured the MIC50

and MIC100 values of all the compounds in the group. They had measurable antimicrobial

effect against Gram-Positive bacteria - comparable with established compounds like

Vancomycin, and measurable interaction with Gram-Negative bacteria, coating the cells

and inhibiting growth.

I then further explored the coating interaction, adding the compounds to bacteria, but also

adding solutions of established antimicrobials, I found that the compound boosted the

efficacy of the established compounds and was also able to overcome resistance

mechanisms developed by the bacteria.

Finally, I developed a modular, 3D printed robot to standardise and increase the accuracy

of the new testing methods.