Genetic complexity alters drug susceptibility of asexual and gametocyte stages of Plasmodium falciparum to antimalarial candidates

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dc.contributor.author Greyling, Nicola
dc.contributor.author Van der Watt, Mariette Elizabeth
dc.contributor.author Gwarinda, Hazel B.
dc.contributor.author Van Heerden, Ashleigh
dc.contributor.author Greenhouse, Bryan
dc.contributor.author Leroy, Didier
dc.contributor.author Niemand, Jandeli
dc.contributor.author Birkholtz, Lyn-Marie
dc.date.accessioned 2025-01-17T07:56:49Z
dc.date.available 2025-01-17T07:56:49Z
dc.date.issued 2024-03
dc.description DATA AVAILABITY STATEMENT: The data sets supporting the conclusions of this article are available from the corresponding authors on reasonable request. en_US
dc.description SUPPORTING INFORMATION: FILE S1: Supplementary Fig S1-S4, Tables S1-S5. en_US
dc.description.abstract Malaria elimination requires interventions able to target both the asexual blood stage (ABS) parasites and transmissible gametocyte stages of Plasmodium falciparum. Lead antimalarial candidates are evaluated against clinical isolates to address key concerns regarding efficacy and to confirm that the current, circulating parasites from endemic regions lack resistance against these candidates. While this has largely been performed on ABS parasites, limited data are available on the transmission-blocking efficacy of compounds with multistage activity. Here, we evaluated the efficacy of lead antimalarial candidates against both ABS parasites and late-stage gametocytes side-by-side, against clinical P. falciparum isolates from southern Africa. We additionally correlated drug efficacy to the genetic diversity of the clinical isolates as determined with a panel of well-characterized, genome-spanning microsatellite markers. Our data indicate varying sensitivities of the isolates to key antimalarial candidates, both for ABS parasites and gametocyte stages. While ABS parasites were efficiently killed, irrespective of genetic complexity, antimalarial candidates lost some gametocytocidal efficacy when the gametocytes originated from genetically complex, multiple-clone infections. This suggests a fitness benefit to multiclone isolates to sustain transmission and reduce drug susceptibility. In conclusion, this is the first study to investigate the efficacy of antimalarial candidates on both ABS parasites and gametocytes from P. falciparum clinical isolates where the influence of parasite genetic complexity is highlighted, ultimately aiding the malaria elimination agenda en_US
dc.description.department Biochemistry, Genetics and Microbiology (BGM) en_US
dc.description.sdg SDG-03:Good heatlh and well-being en_US
dc.description.sdg SDG-09: Industry, innovation and infrastructure en_US
dc.description.uri https://journals.asm.org/journal/aac en_US
dc.identifier.citation Greyling, N., Van der Watt, M., Gwarinda, H., Van Heerden, A., Greenhouse, B., Leroy, D., Niemand, J., Birkholtz, L.M. & John, A.O. Genetic complexity alters drug susceptibility of asexual and gametocyte stages of Plasmodium falciparum to antimalarial candidates. Antimicrobial Agents and Chemotherapy. 2024 Mar 6; 68(3): e0129123. doi: 10.1128/aac.01291-23. en_US
dc.identifier.issn 0066-4804 (print)
dc.identifier.issn 1098-6596 (online)
dc.identifier.other 10.1128/aac.01291-23
dc.identifier.uri http://hdl.handle.net/2263/100129
dc.language.iso en en_US
dc.publisher American Society for Microbiology en_US
dc.rights © 2024 Greyling et al. This is an openaccess article distributed under the terms of the Creative Commons Attribution 4.0 International license. en_US
dc.subject Plasmodium falciparum en_US
dc.subject Clinical isolates en_US
dc.subject Gametocytes en_US
dc.subject Differential compound sensitivity en_US
dc.subject Genetic diversity en_US
dc.subject Malaria en_US
dc.subject SDG-03: Good health and well-being en_US
dc.subject SDG-09: Industry, innovation and infrastructure en_US
dc.title Genetic complexity alters drug susceptibility of asexual and gametocyte stages of Plasmodium falciparum to antimalarial candidates en_US
dc.type Article en_US


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