Su-Mari Du Plessis Poster 2023

Ms Su-Mari Du Plessis

 

 

Stellenbosch University, South Africa

Biomimetic nanoparticle-based host-directed therapy for the eradication of Mycobacterium tuberculosis

Poster Abstract

Su-Mari du Plessis1, Admire Dube2, Josh Reineke3, Nelita du Plessis1 and Samantha L. Sampson1

Current lengthy and unpredictable Tuberculosis (TB) treatment regimens leading to poor adherence and the ongoing emergence of antibiotic resistance desperately calls for alternative strategies. One being host directed therapeutic (HDT) approaches through the use of biomimetic nanoparticles (NPs). We hypothesize that biomimetic NPs will reduce intracellular M. tuberculosis (Mtb) numbers and instead of targeting the bacilli itself the host cell becomes the target consequently boosting the cells’ innate ability to kill invading pathogens. This study aims to assess the antibacterial effects of the NPs on intracellular M. tuberculosis and further clarify the stimulated immune pathways that contribute towards NP efficacy.

We will utilize RAW264.7 macrophages as well as bone marrow derived macrophages isolated from C3HeB/FeJ mice as host cell representatives. The NPs to be used will either have a polymer or a metal organic framework core and will be surface functionalized with curdlan or mycolic acid. First, we will assess the safety of the various biomimetic NP formulations at different concentrations, using flow cytometry, on the host cells to determine which non-toxic particle formulations to use for downstream analysis. Afterwards, macrophages will be infected with Mtb, containing a LuxABCDE gene that will providing luminescent readouts as a proxy for cell number. Up to 10 non-toxic NP formulations will be administered to determine anti-mycobacterial activity over a 72h period. Once anti-mycobacterial activity is detected, cytokine production, intracellular acidification and phagolysosome formation will be investigated as possible antibacterial pathways.

The results will contribute towards the development and successful identification of possible biomimetic NP formulations that could provide an alternative HDT approach towards the treatment and eradication of TB.   Furthermore, the results from this study will provide the basis for further in vivo studies using mice.

 

Biography

I am a final year PhD student at Stellenbosch University. I completed my undergraduate, BSc (Hons) as well as MSc degrees at Stellenbosch University, majoring in microbiology, and have been working on biomimetic nanoparticles for the past 5 years under the supervision of Prof. Samantha Sampson. My current research is focused on nanoparticle host directed therapeutic approaches for the treatment of Tuberculosis. I am interested in tissue culture work, the mechanisms surrounding bacterial mimicry and nanomedicine and how such therapeutic approaches could be a breakthrough in the treatment of TB and other intracellular diseases.