Research Articles (Biochemistry, Genetics and Microbiology (BGM))
Permanent URI for this collectionhttp://hdl.handle.net/2263/87805
Browse
Recent Submissions
Now showing 1 - 20 of 714
Item Polyploid-diploid coexistence in the greater duckweed Spirodela polyrhiza(Wiley, 2025) Mortier, Frederik; Van de Peer, Yves; Bonte, DriesPolyploidy is widespread among plants and is often associated with stressful environments that can facilitate their establishment. Successful new polyploids must overcome competitive disadvantages against their progenitors or benefit from negative frequency-dependent growth. We tested the invasion of neotetraploid duckweed strains (Spirodela polyrhiza) into populations of their diploid progenitors in control and salt stress conditions in replicated microcosms. We also tested the reverse scenario: invasion of diploids in neotetraploid populations, to examine the impact of the initial tetraploid proportion. Tetraploid proportions declined in all tetraploid and diploid invasions, with different rates than predicted from only intrinsic growth rate differences. Salt stress affected the decline in a strain-specific manner. We found evidence for negative frequency-dependent growth that, nonetheless, was insufficient to overcome competitive disadvantages of neopolyploids. SYNTHESIS. Our findings demonstrate the crucial role of competition and frequency dependence on neopolyploid establishment. Therefore, we caution against inferring neopolyploid success based solely on intrinsic growth rates.Item High genetic diversity and limited regional population differentiation in populations of Calonectria pseudoreteaudii from Eucalyptus plantations(American Phytopathological Society, 2025-01) Li, WenWen; Liu, Feifei; Chen, ShuaiFei; Wingfield, Michael J.; Duong, Tuan A.Calonectria pseudoreteaudii causes a serious and widespread disease known as Calonectria leaf blight in Eucalyptus plantations of southern China. Little is known regarding the population biology or reproductive biology of this pathogen in the affected areas. The aims of this study were to investigate the genetic diversity, population structure, and reproductive mode of C. pseudoreteaudii from affected Eucalyptus plantations of southern China. Ten polymorphic simple sequence repeat markers were developed for the species and were used to genotype 311 isolates from eight populations. The mating types of all isolates were identified using the MAT gene primers. The results revealed a high level of genetic diversity of the pathogen in all investigated populations. Of the 90 multilocus genotypes detected, 10 were shared between at least two populations. With the exception of one population from HuiZhou, GuangDong (7HZ), the most dominant genotype was shared in the seven remaining populations. Discriminant analysis of principal components and population differentiation analyses showed that the 7HZ population was well differentiated from the others and that there was no significant differentiation between the remaining populations. Analysis of molecular variance suggested that most molecular variation was within populations (86%). Index of association analysis was consistent with a predominantly asexual life cycle for C. pseudoreteaudii in the studied regions. Although both mating types were detected in seven of the eight populations, the MAT1-1/MAT1-2 ratios in these populations deviated significantly from the 1:1 ratio expected in a randomly mating population.Item Advancing forest pathology : the need for community-driven molecular experimental model systems(Wiley, 2025-08) Oostlander, Anne G.; Fleissner, Andre; Slippers, Bernard; bernard.slippers@fabi.up.ac.zaForests world-wide are under escalating threat from emerging and invasive fungal and oomycete pathogens, driven by globalization and shifting climate dynamics. Effective strategies to manage the current scale and rate of changes in forest health remain hindered by our limited ability to study the underlying mechanisms of pathogen–host and pathogen–microbiome interactions, especially at a molecular and cellular level, compared to general plant pathology, where experimental and model systems exist. Such models facilitate the integration of diverse methodologies from a broader base of the research community, allowing for a more holistic and deeper examination of complex research questions. Here, we propose a framework for the development of such model systems also for forest pathology. This goal is more feasible than ever, thanks to rapid technological advancements, increasing open data availability and a globally interconnected research community. These factors create a unique opportunity to integrate ecosystem-focused research in forest pathology with a unified model organism strategy. Achieving this goal will require a dedicated community effort in the coming years, as such model systems are not discovered but built.Item Expanding ISME communications to taxonomy and nomenclature(Oxford University Press, 2025-06) Chuvochina, Maria; Palmer, Marike; Venter, S.N. (Stephanus Nicolaas)Research in microbial ecology is often accompanied by the classification and naming of new taxa, typically included as part of the results section of an ecological study. Bold and beautiful, Latin names are more than labels—they are essential tools for scientific communication. Nested within a hierarchical system, they populate public databases and enable researchers to search for organisms, retrieve associated sequences and metadata, and explore related taxa across various taxonomic levels. In recognition of the vital role that naming and classification play in ecological studies, ISME Communications is proud to introduce Taxonomy and Nomenclature as part of its scope.Item First report of Clavibacter nebraskensis causing Goss's bacterial leaf blight on maize (Zea mays) in South Africa(American Phytopathological Society, 2025-07) Coertze, Sonja; Coetzee, Beatrix; Basson, Elaine; De Villiers, Dore; Makhura, Tjitjila; Mostert, Diane; Slippers, Bernard; Rose, Lindy J.; Visagie, Cobus M.; Read, David AlanNo abstract available.Item Host specificity and host stage preference of Psyllaephagus species (Hymenoptera: Encyrtidae) towards invasive eucalypt psyllids (Hemiptera: Aphalaridae)(Wiley, 2025-08) Makunde, Privilege Tungamirai; Slippers, Bernard; Bush, Samantha J.; Hurley, Brett Phillip; privilege.makunde@up.ac.zaInvasive eucalypt psyllids pose a threat to the long-term production of eucalypts worldwide. In order to reduce their economic impact, classical biological control using Psyllaephagus species has been used successfully. The objectives of this study were to determine the host specificity and host stage preference of Psyllaephagus blastopsyllae, Psyllaephagus pilosus and Psyllaephagus bliteus using related eucalypt-feeding psyllids, Blastopsylla occidentalis, Ctenarytaina eucalypti, Glycaspis brimblecombei and Spondyliaspis cf. plicatuloides. To determine host specificity, three Psyllaephagus species were collected locally from their hosts. Five-day-old parasitoids were exposed to all five developmental stages (I–V) of host and non-host psyllids in choice and non-choice tests. Similar bioassays were used to assess parasitoid preferences for specific nymphal stages, identifying their preferred developmental stages of potential hosts. Glycaspis brimblecombei was identified as a potential host for P. blastopsyllae, and S. cf. plicatuloides as an alternate host for P. bliteus, though emergence rates were three to four times lower than for their known hosts. Psyllaephagus pilosus showed no interest in non-host psyllids. Female parasitoids displayed stage-specific preferences for both known and newly identified hosts. The current findings indicate that some Psyllaephagus species attack hosts within an ecological niche, whereas others are highly host specific. Additionally, the distinction between potential host range observed in laboratory conditions and ecological host range in field conditions should be considered, as laboratory tests typically exhibit a broader host range.Item In silico docking and ADMET studies on clinical targets for type 2 diabetes correlated to in vitro inhibition of pancreatic alpha-amylase and alpha-glucosidase by rutin, caffeic acid, p-coumaric acid, and vanillin(Springer, 2025-03) Mcmillan, Jamie; Bester, Megan Jean; Apostolides, Zeno; u16016760@tuks.co.zaPlease read abstract in the article.Item The population genetic structure of Ficus craterostoma in South Africa(Elsevier, 2025-03) Deng, Jun-Yin; Van Noort, Simon; Compton, Stephen G.; Chen, Yan; Greeff, Jacobus Maree; jaco.greeff@up.ac.zaIn the eastern part of its distribution, Ficus craterostoma occurs in Afromontane forests whereas it also occurs in low-lying scarp and Indian Ocean coastal belt forests in South Africa. Ficus craterostoma must have dispersed to these low-lying forests from the Afromontane forests, even though forests became highly fragmented during the Pleistocene. To understand how these ancient changes have impacted the distribution and population structure of F. craterostoma we quantified the genetic variation in its slow-evolving chloroplast DNA with limited dispersal ability via seeds, and its highly variable nuclear microsatellites that reflect exceptional pollen flow. The chloroplast variation was highly structured and frequently monomorphic in nearby forests while the nuclear variation showed little structure and isolation by distance. From these data we reach several conclusions. Ficus craterostoma may have become extinct from South Africa's northern Afromontane forests during the Pleistocene. These forests were possibly subsequently recolonized from southern forests that may have been scarp or Afromontane in nature. Additionally, there was one scarp and one Indian Ocean coastal belt forest refugium, both of which were very isolated and small. Nuclear gene flow caused by pollen flow is very effective along the western part of the South African population, knitting together Afromontane and scarp forest fragments, dispersed over 1000 km, into one genetic population. Conversely, the Indian Ocean coastal belt forest refugium appears to have been isolated in terms of gene flow, but more recent gene flow with two nearby inland forests may have started to homogenize their genetic variation. Due to the unusual pollination system of fig trees, other forest tree species may display very different dynamics. HIGHLIGHTS • In South Africa Ficus craterostoma inhabits Afromontane, scarp and coastal forests. • Genetic data suggest that F. craterostoma was affected profoundly by the ice ages. • Large F. craterostoma populations survived in southern scarp forests. • This tree may have recolonized Afromontane forests from the south. • Coastal forest populations of F. craterostoma are isolated and unique.Item The slow pandemic : emergence of antimicrobial resistance in the postadvent of SARS-CoV-2 pandemic(Wiley, 2025-04) Osunla, Ayodeji; Oloye, Femi; Kayode, Adeoye John; Femi-Oloye, Oluwabunmi; Okiti, Ayomide; Servos, Mark; Giesy, JohnBACKGROUND : The unprecedented outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has dramatically changed the global approach to public health, emphasizing the importance of measures to control and prevent infections. In response to the COVID-19 crisis, stringent hygiene practices and surface disinfection have become the norm, with an unprecedented surge in the use of disinfectants and antiseptics (DAs). MAIN TEXT : While these measures have been crucial in curbing the spread of the virus, an emerging concern has taken center stage: the potential impact of the prolonged and widespread use of antimicrobial compounds in these products on the development of antibiotic resistance. Antimicrobial resistance (AMR) has long been recognized as one of the most pressing global health threats. Quaternary ammonium compounds (QAC) such as benzalkonium chloride, benzethonium chloride, and cetylpyridinium chloride, which are extensively used in DAs formulations, have gained less attention in the context of AMR. CONCLUSION : A high abundance of QACs was detected in wastewater, and certain bacteria such as Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterococcus species developed resistance to these compounds over time. We analyzed the available evidence from the scientific literature, examining the presence and concentrations of QACs in different water sources, and their resistance mechanisms. This review aimed to shed light on the multifaceted challenges that arise from the dual battle against the COVID-19 pandemic and the ongoing global fight against AMR.Item Multilocus sequence typing and antimicrobial susceptibility of Listeria monocytogenes isolated from foods surveyed in Kosovo(MDPI, 2024-12) Jashari, Besart; Stessl, Beatrix; Felix, Benjamin; Cana, Armend; Bisha, Bledar; Jankuloski, Dean; Blagoevska, Katerina; Kayode, Adeoye JohnIn the absence of data on the reporting of L. monocytogenes resistance to antibiotics, we sought to determine which clonal complexes (CCs)/sequence types (STs) circulate in the food chain in Kosovo and to determine their antibiogram profiles to a panel of 18 antibiotics. From a total of 114 isolates, 21 different typical STs were identified by multilocus sequence typing (MLST). Each isolate derived from the food categories was subjected to tests to verify its susceptibility to the selected antibiotics according to the designed Sensititre GPN3F panel. Among the different STs that were identified, CC9-ST9 was more abundant in meat products (38.75%) while CC29-ST29 was more abundant (24.0%) in dairy products. Moreover, these isolates showed marked resistance against levofloxacin (22.8%), gentamicin and rifampicin (17.5%), quinupristin/dalfopristin (14.9%), erythromycin (11.4%), penicillin (7.89%), tetracycline (1.75%), and streptomycin (0.88%). A total of 27 multiple antibiotic resistance (MAR) phenotypes were observed amongst the isolates, which ranged from 3 to 12. The ARI of the food category including meat and meat products (MMP, 0.22) and fish meat products (FMP, 0.26) were >0.2, the permissible Krumperman threshold. The number of strains with MAR values >0.2 was 34, (29.8%). The identification of typical multidrug-resistant STs among L. monocytogenes isolates in Kosovo constitutes a potential threat to food safety and public health, which requiresItem Synergizing ecotoxicology and microbiome data is key for developing global indicators of environmental antimicrobial resistance(Springer, 2024-12) Makumbi, John Paul; Leareng, Samuel K.; Pierneef, Rian Ewald; Makhalanyane, Thulani PeterThe One Health concept recognises the interconnectedness of humans, plants, animals and the environment. Recent research strongly supports the idea that the environment serves as a significant reservoir for antimicrobial resistance (AMR). However, the complexity of natural environments makes efforts at AMR public health risk assessment difficult. We lack sufficient data on key ecological parameters that influence AMR, as well as the primary proxies necessary for evaluating risks to human health. Developing environmental AMR ‘early warning systems’ requires models with well-defined parameters. This is necessary to support the implementation of clear and targeted interventions. In this review, we provide a comprehensive overview of the current tools used globally for environmental AMR human health risk assessment and the underlying knowledge gaps. We highlight the urgent need for standardised, cost-effective risk assessment frameworks that are adaptable across different environments and regions to enhance comparability and reliability. These frameworks must also account for previously understudied AMR sources, such as horticulture, and emerging threats like climate change. In addition, integrating traditional ecotoxicology with modern ‘omics’ approaches will be essential for developing more comprehensive risk models and informing targeted AMR mitigation strategies.Item Two triterpenoids, ARM-2 and RA-5, from Protorhus longifolia exhibit the potential to modulate lipolysis and lipogenesis in cultured 3T3-L1 adipocytes(Wiley, 2024-10) Ndlovu, Musawenkosi; Serem, June Cheptoo; Bester, Megan; Apostolides, Zeno; Opoku, Andrew R.; Mosa, Rebamang AnthonyTriterpenoids have been identified as potential novel lipid-lowering drugs for the treatment of hypertriglyceridemia. This study investigated the potential antilipogenic and/or antilipolytic effects of two triterpenoids (ARM-2 and RA-5) isolated from the stem bark of Protorhus longifolia (Benrh.) Engl. Employing a combination of in silico predictions and in vitro assays, the interactions between these triterpenoids and key proteins involved in lipogenesis and lipolysis were investigated. In silico molecular docking analysis predicted a favourable binding affinity of both triterpenoids to PPARγ, SREBP-1, and AMPK, with lower binding affinity to C/EBPα, pancreatic lipase, and hormone-sensitive lipase (HSL). Both triterpenoids exhibited in vitro inhibition of pancreatic lipase with Ki and IC50 values ranging from 28.7 to 52.9 μM and 27.6 to 35.8 μM, respectively. Total and neutral lipid accumulation in differentiated 3T3-L1 adipocytes and the oleic acid-induced HepG2 cell model was inhibited, with ARM-2 showing better inhibition than RA-5. In the HepG2 model, the inhibitory activity of the two triterpenoids (at 25 and 100 μM) was comparable to 50 μM lovastatin, although the latter was cytotoxic, whereas both ARM-2 and RA-2 lacked cytotoxicity. Associated gene expression was similar to the effect of simvastatin where the expression of SREBP-1, PPARγ, C/EBPα, and HSL was reduced and that of AMPK was unchanged. In vitro studies confirmed that ARM-2 and RA-5 also inhibited adipocyte lipolysis, where the reduction in glycerol release by 25 and 100 μM was similar to 50 μM lovastatin and simvastatin. This study identifies that the triterpenoids, ARM-2 and RA-5, have the potential to modulate lipogenesis and lipolysis.Item The ATM kinase inhibitor AZD0156 is a potent inhibitor of Plasmodium falciparum phosphatidylinositol 4-kinase (PI4Kβ) and is an attractive candidate for medicinal chemistry optimization against malaria(Wiley, 2025-07) Woodland, John G.; Coertzen, Dina; Wicht, Kathryn J.; Hidalgo, Virginia Franco; Pasaje, Charisse Flerida A.; Godoy, Luiz C.; Qahash, Tarrick; Mmonwa, Mmakwena M.; Dziwornu, Godwin A.; Wambua, Lynn; Harries, Sarah; Korkor, Constance M.; Njoroge, Mathew; Krugmann, Liezl; Taylor, Dale; Leshabane, Meta Kgaogelo; Langeveld, Henrico; Rabie, Tayla Anne; Reader, Janette; Van der Watt, Mariette Elizabeth; Venter, Nelius; Erlank, Erica; Aswat, Ayesha S.; Koekemoer, Lizette L.; Yeo, Tomas; Jeon, Jin H.; Fidock, David A.; Gamo, Francisco Javier; Wittlin, Sergio; Niles, Jacquin C.; Llinas, Manuel; Coulson, Lauren B.; Birkholtz, Lyn-Marie; Chibale, Kelly; lynmarie.birkholtz@up.ac.zaNew compounds targeting human malaria parasites are critical for effective malaria control and elimination. Here, we pursued the imidazoquinolinone AZD0156 (MMV1580483), a human ataxia-telangiectasia mutated (ATM) kinase inhibitor that completed Phase I clinical trials as an anticancer agent. We validated its in vitro activity against the two main forms of the Plasmodium falciparum parasite in the human host, viz. the asexual blood (symptomatic) stage and sexual gametocyte (transmission) stage. Resistance selection, cross-resistance, biochemical, and conditional knockdown studies revealed that AZD0156 inhibits P. falciparum phosphatidylinositol 4-kinase type III beta (PfPI4Kβ), a clinically-validated target for the treatment of malaria. Metabolic perturbations, fixed-ratio isobolograms, killing kinetics and morphological evaluation correlated AZD0156 inhibition with other known PI4Kβ inhibitors. The compound showed favorable in vivo pharmacokinetic properties and 81% antimalarial efficacy (4 × 50 mg kg−1) in a P. berghei mouse malaria infection model. Importantly, a cleaner biochemical profile was measured against human kinases (MAP4K4, MINK1) implicated in embryofoetal developmental toxicity associated with the PfPI4Kβ inhibitor MMV390048. This improved kinase selectivity profile and structural differentiation from other PI4Kβ inhibitors, together with its multistage antiplasmodial activity and favorable pharmacokinetic properties, makes AZD0156 an attractive candidate for target-based drug repositioning against malaria via a medicinal chemistry optimization approach.Item Uncovering cryptic species diversity of Ophiocordyceps (Ophiocordycipitaceae) associated with Coleoptera from Thailand(Westerdijk Fungal Biodiversity Institute, 2024-12) Mongkolsamrit, S.; Noisripoom, W.; Tasanathai, K.; Khonsanit, A.; Thanakitpipattana, D.; Lamlertthon, S.; Himaman, W.; Crous, Pedro W.; Stadler, M.; Luangsa-ard, J.J.This study advances our understanding of Ophiocordyceps, an extensively studied entomopathogenic fungus within the Ophiocordycipitaceae, particularly in Thailand. We introduce seven novel species associated with Coleoptera - O. albostroma, O. brunnea, O. capilliformis, O. kohchangensis, O. phitsanulokensis, O. pseudovariabilis, and O. ratchaburiensis. Remarkably, O. brunnea, O. kohchangensis, and O. ratchaburiensis exhibit ascomata on the subterminal region of the stromata, with the asexual form appearing at the apex of the stipe, reminiscent of O. brunneipunctata. In contrast, O. phitsanulokensis produces its ascomata in the upper region of the stipe. Shared traits include immersed perithecia and part-spores production. Ophiocordyceps albostroma and O. pseudovariabilis produce pseudo-immersed perithecia, with the former producing ascospores breaking into four part-spores, and the latter displaying 32 part-spores. Ophiocordyceps capilliformis is also introduced due to morphological distinctions from closely related species. Phylogenetic analyses based on multigene loci (LSU, TEF1, RPB1, RPB2) robustly confirm the placement of these new species within Ophiocordyceps. Additionally, we report a new record of O. clavata in Thailand.Item A phylogenetic assessment of Akanthomyces sensu lato in Cordycipitaceae (Hypocreales, Sordariomycetes) : introduction of new genera, and the resurrection of Lecanicillium(Westerdijk Fungal Biodiversity Institute, 2024-12) Khonsanit, A.; Thanakitpipattana, D.; Mongkolsamrit, S.; Kobmoo, N.; Phosrithong, N.; Samson, R.A.; Crous, Pedro W.; Luangsa-ard, J.J.During entomopathogenic fungal surveys conducted in Thailand, 15 specimens tentatively classified under Akanthomyces sensu lato were identified. To gain a comprehensive understanding of their taxonomy, molecular phylogenies using combined LSU, TEF1, RPB1, and RPB2 sequence data, together with morphological examination of several Akanthomyces spp. from previous studies were conducted. The analyses revealed distinct clades representing independent lineages within the Cordycipitaceae. These clades were further characterized by different asexual morph types and the respective hosts they parasitize. In this context, we resurrected the genus Lecanicillium to accommodate 12 known species previously classified under Akanthomyces sensu lato, found on diverse hosts. We propose four new genera - Corniculantispora, Corpulentispora, Zarea, and Zouia - from species previously identified as Lecanicillium. Notably, certain Akanthomyces species associated with spiders and parasitic on Ophiocordyceps sinensis were reclassified into the new genera Arachnidicola and Kanoksria, respectively. Moreover, we introduce four novel species in Akanthomyces sensu stricto found across a diverse range of moth families: Ak. buriramensis, Ak. fusiformis, Ak. niveus, and Ak. phariformis. Additionally, we provide descriptions and illustrations of the sexual morph linked to Ak. laosensis and Ak. pseudonoctuidarum, along with a second type of synnemata seen in Ak. noctuidarum and Ak. pseudonoctuidarum. To assist with their identification, keys to the genera Akanthomyces, Arachnidicola, and Lecanicillium are provided, but should not be used to replace molecular identificationItem Endophytic diaporthe species from Brazil(Westerdijk Fungal Biodiversity Institute, 2024-12) Ferro, L.O.; Bezerra, J.D.P.; Da Silva, T.M.; De Oliveira, C.S.; Nascimento, S.dosS.; Paiva, L.M.; Fan, x.; Crous, Pedro W.; Souza-Motta, C.M.Diaporthe species can inhabit various hosts with different lifestyles and live as endophytes, pathogens, and saprobes. Our study analysed 180 endophytic Diaporthe isolates from Miconia sp. in the Atlantic Forest, Brosimum gaudichaudii in the Brazilian savanna (Cerrado), and Anacardium occidentale in the Caatinga forest and Cerrado in Brazil. Based on multi-locus phylogenetic analyses [β-tubulin (tub2), internal transcribed spacer regions and intervening 5.8S rRNA (ITS), translation elongation factor 1-alpha (tef1), calmodulin (cmdA), and histone (his3)] and morphological features, we are introducing seven new species (D. azevedoi, D. catimbauensis, D. coracoralinae, D. luizorum, D. pedratalhadensis, D. samambaiaensis, and D. vargemgrandensis) and reporting seven known species (D. fructicola, D. inconspicua, D. infertilis, D. paranensis, D. raonikayaporum, D. schini, and D. ueckeri). We also included a morphological description of D. infertilis and synonymised D. lutescens, D. pseudoinconspicua, and D. samaneae under D. inconspicua; D. neoraonikayoporum under D. raonikayaporum; and D. passifloricola, D. rosae, and D. vochysiae under D. ueckeri, based on limited nucleotide differences among DNA sequence data and overlapping morphological features. Our results highlight the importance of including endophytic isolates in the phylogeny of Diaporthe, and show how these data expand the geographic distribution and host relationships of known species.Item Historical constraints and heterospecific interference lead to maladaptive sex ratio changes in a pollinating fig wasp(Royal Society, 2025-07) Greeff, Jacobus Maree; Mnguni, Simiso Polite; Warren, MarieNatural selection’s power is beautifully illustrated by sex ratio variation that seems near-perfectly adapted. However, the fit of sex ratios to optimal predictions is usually tested in oversimplified ecological settings. This creates a one-sided view of evolution, where details are ignored, and evolution appears to produce optimal solutions. Entertaining maladaptation as a potential explanation allows consideration of historical contingencies and trade-offs. These become important in realistic settings where traits may need to be multifunctional, and historical contingencies may channel evolution to suboptimal phenotypes. Evaluating traits’ adaptive/maladaptive nature requires understanding the underlying mechanisms (the proximate causes). We studied clutch composition in a pollinating fig wasp where heterospecific females potentially interfere with sex ratio production and adjustment. Using an information-theoretic approach, we compared hypotheses and confirmed that heterospecific females disrupt Ceratosolen arabicus females’ sex ratios. Given the high fitness costs of failing to adjust optimally, we argue this maladaptation stems from rudimentary mechanisms that fail in realistic conditions and are thus forced to be multifunctional, creating fitness trade-offs. Our findings highlight how historical constraints and ecological interactions may limit adaptation, challenging the assumption that selection always produces optimal traits. Furthermore, they emphasize the need to incorporate ecological complexity when testing evolutionary predictions.Item First record of the white root rot fungus Dematophora necatrix on indigenous South African trees(Springer, 2025-05) Balocchi, Felipe; Wingfield, Michael J.; Paap, Trudy; felipe.balocchi@fabi.up.ac.zaThe soilborne fungus Dematophora (=Rosellinia) necatrix and causal agent of white root rot, has a wide host range that includes many tree species of economic importance. The pathogen has a worldwide distribution, including reports from commercial orchards in South Africa since the 1970s. During tree health surveys conducted as part of a sentinel plant project, we detected the pathogen on two symptomatic individuals from the indigenous South African tree species Diospyros whyteana and Noronhia foveolata subsp. major. Observed symptoms included wilting and root rot, with characteristic white mycelium present under the bark. Dematophora necatrix was isolated from both hosts and its identity confirmed by sequencing two gene regions (ITS and actin). Pathogenicity was confirmed through inoculation tests under semi-controlled conditions by inoculating the soil with bamboo sticks colonized with the fungus. Plants of both species developed similar symptoms to those observed naturally, and the fungus was successfully recovered from all symptomatic plants. This is the first record in South Africa of D. necatrix on indigenous species and outside of commercial orchards. Given the environmental threat posed we recommend the fungus is considered for regulation in South Africa.Item Medicinal chemistry progression of sapanisertib, the anticancer and dual Plasmodium phosphatidylinositol 4-kinase beta and cGMP-dependent protein kinase inhibitor, for malaria(American Chemical Society, 2025-06) Gachuhi, Samuel; Kamunya, Stephanie; Fienberg, Stephen; Wambua, Lynn; Salomane, Nicolaas; Mayoka, Godfrey; Taylor, Dale; Coertzen, Dina; Van der Watt, Mariette Elizabeth; Reader, Janette; Birkholtz, Lyn-Marie; Wittlin, Sergio; Krugmann, Liezl; Coulson, Lauren B.; Chibale, KellyWe recently demonstrated that the anticancer human mTOR inhibitor sapanisertib displays antimalarial activity in a malaria mouse model of infection and inhibits multiple Plasmodium kinases, including the high-value targets phosphatidylinositol 4-kinase type III beta (PI4Kβ) and cGMP-dependent protein kinase (PKG). Herein, we explore structure-activity relationships for sapanisertib analogues with benzyl and pyridyl substituents at the 7-position of the pyrazolopyrimidine core. New analogues with improved safety profiles were identified, including analogues with dual Plasmodium PI4Kβ and PKG inhibitory activity (exemplified by 19), as well as potent Plasmodium PI4Kβ inhibitors with minimal inhibitory activity against PKG (exemplified by 20). Compound 19 displayed potent antiplasmodium activity, high microsomal metabolic stability, and a good safety profile (hERG IC50 > 30; cytotoxicity selectivity index = 99). In vivo proof-of-concept, where a 4 × 50 mg kg-1 oral dose of 19 resulted in an 80% reduction in parasitemia in P. berghei-infected mice, further demonstrated the lead potential of this series. against respiratory-related infections with economic potential.Item The synthesis and investigation of novel 3-benzoylbenzofurans and pyrazole derivatives for anti-HIV activity(Royal Society of Chemistry, 2025-05) Khuzwayo, Sinothile S.; Selepe, Mamoalosi A.; Meyer, Debra; Gama, Ntombenhle HlengiwePlease read abstract in the article.