Zimvo Obasa Poster 2024
Dr Zimvo Obasa
Stellenbosch University, South Africa
An Ex Vivo Model for Understanding the Impact of Vaccination on Mycobacterial Persister Populations
Poster Abstract
Ex vivo mycobacterial growth inhibition assays (MGIAs) have been successfully exploited to assess vaccine efficacy, probe immune mechanisms underlying protective efficacy, and determine the combined impact of drug treatment and vaccination on mycobacterial killing. An important question that MGIAs lend themselves to, but has not yet been addressed, is what effect immune status (e.g. vaccination) might have on mycobacterial persisters. During TB treatment, the majority of drug susceptible Mycobacterium tuberculosis is killed within the first few days of treatment, but the small remaining (persister) population takes much longer to eradicate, necessitating a minimum treatment period of 6 months. In many individuals, initial infection does not immediately proceed to active disease, and persistent bacteria may underlie latent TB infections. Whether they form after TB treatment or because of host pressure, persisters pose a subsequent threat of reactivation disease, a particular concern in HIV-co-infected individuals.
We have recently developed a dual fluorescent replication reporter system and applied this to demonstrate Mtb persister formation in infected macrophages. This has been introduced into several mycobacterial strains, including Mtb H37Rv and clinical isolates of Mtb and M. bovis, and allows us to track the formation, survival or killing of the persister subset alongside actively replicating bacteria. These reporter strains in combination with flow cytometry provide a rapid means of monitoring population wide Mtb growth, killing kinetics and phenotypes on a single cell level. In this work, we are adapting MGIAs to assess the impact of the change in immune cell populations after vaccination on mycobacterial persister populations. This work could provide new insights into the impact of host factors on persister formation, and vice versa. This would help to rationally design new vaccines and adjunct therapies that reduce persister formation and therefore increase long-term protection against TB.
Biography
Dr Zimvo Obasa is a postdoctoral researcher at Stellenbosch University, specializing in Molecular Biology. She holds a BSc degree in Human Life Sciences (2014), an MSc in Human Physiology (2017), and a PhD in Molecular Biology (2021). During her doctoral studies, Dr. Obasa focused on elucidating host immune responses triggered by Mycobacterium tuberculosis persisters in macrophage cultures. She also developed and validated a trackable murine model for studying Mycobacterium persister formation in Balb/c mice. Currently, her postdoctoral research is centered on evaluating the in vivo response to and efficacy of novel nanoparticle (NP) formulations as a host-directed therapy for eradicating all forms of Mycobacterium tuberculosis in C3HeB/FeJ (Kramink) mice. By utilizing the Kramnik mouse strain, Dr. Obasa aims to assess the impact of NPs on immuno-pathology and vice versa. Her work holds promise in contributing to the advancement of tuberculosis control strategies, particularly in developing more effective drug treatment regimens.
