ResearchSpace
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Exploring the inhibitory potential of South African natural compounds against Mycobacterium tuberculosis fatty acyl- AMP ligase.
(2025) Matshoba, Mbali.; Mhlongo, Ndumiso Nhlakanipho.
Background: Tuberculosis is one of the leading infectious diseases causing mortality worldwide. Factors such as the increasing prevalence of drug-resistant strains and toxicity profiles of current drugs have made it nearly impossible to eradicate TB. This calls for urgent discovery and development of potent and safe tuberculosis drug candidates with a novel mechanism of action. Usage of natural compounds and their derivatives is being prioritized for drug development owing to their accessibility, potency, and safety profiles.
Aim: To identify natural inhibitors of M. tuberculosis FadD23 and characterize their potential mechanism of inhibition.
Methodology: A crystal structure of FaD23 (PDB ID 8hdf) with a resolution of 2.2 Å was obtained from RCSB Protein Data Bank. Virtual screening of seven antitubercular compounds from the South African Natural Compounds Database (SANCDB), namely SANC00937, SANC00520, SANC00522, SANC00519, SANC00834, SANC01098, and SANC01097, was performed using molecular docking principles to identify potential inhibitors of FadD23. FadD23-docked compounds underwent 130 ns molecular dynamics (MD) simulation using Amber18 software package. MD trajectories from simulations were used to calculate MM/GBSA binding free energy to determine binding affinities of compounds to FadD23. Various metrics, including root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), hydrogen bonding, and secondary structure elements, were used to characterise conformational dynamics between FadD23-ligand complexes under simulated physiological conditions. The safety profile of the simulated compounds was also evaluated using the SwissADME and ProTox 3.0 servers.
Results: The docking results identified compound SANC00937, a flavonoid, as a top candidate that effectively binds at the ATP-binding site of FadD23 with the highest docking score of -8.4 kcal/mol, stabilized by hydrophobic and hydrogen-bond interactions. To achieve accuracy of docking results, all docked compounds were subjected to 130 ns MD simulations to further characterize their interaction with the protein. MM/GBSA calculations revealed SANC01098 to have the highest binding affinity of -28.86 kcal/mol to the protein with reference to ANP. However, SANC01098 resided adjacent to the ATP binding site. SANC00937 showed a second highest binding affinity of -27.83 kcal/mol with reference to ANP, and interacted with key ATP-binding site residues Ala328, Asp222, Gly330, and Ser300 which significantly contributed to a stronger binding affinity and a more stable interaction with FadD23. All complexes exhibited RMSd values below 2 Å highlighting stable association of ligands with the protein. However, the average Rg and RMSd values indicated that SANC01098 forms a more stable association with FadD23 than ANP, suggesting a possibility of competitive binding between SANC00937 and ATP. The secondary structure analysis revealed that SANC00937 deforms the Pi structural component of FadD23, optimizing its binding affinity within the binding site. This was alsosu pported by large hydrophobic interactions and few hydrogen bonds that stabilized FadD23- SANC00937 complex. Pharmacokinetic evaluation showed that SANC01097 exhibits optimal oral drug-like properties, characterized by a high bioavailability score, minimal interference with major Cytochrome P-450 enzymes.
Conclusion: This study has identified SANC00937 as a potential ligand to interfere with FadD23 function by competing and displacing ATP in the active site. This opens an interest in experimental evaluation of this natural compound for drug-like properties against FadD23. A positive outcome of such evaluation could potentially lead to the development of novel, alternative and naturally safe TB therapeutics that are accessible in abundance to Africans. In absence of an approved FadD23 inhibitors, these results provide a lead baseline for further laboratory-based experiments to confirm the biological relevance of both SANC00937 and SANC01098 compounds as potential inhibitors of FadD23.
Experiences of young audiologists on continuing professional development in the private sector in KwaZulu-Natal, South Africa.
(2024) Barath, Suvishka.; Ross, Andrew John.
Background
Continuing Professional Development (CPD) is an ongoing learning process that builds on initial training and education and is dedicated to improving competency. Low compliance rates of audiologists adhering to CPD have been reported by the Health Professionals Council of South Africa (HPCSA). However, there is an absence of research on CPD from the perspective of audiologists working in the private sector. Furthermore, the low compliance rates need to be investigated to establish the barriers that audiologists encounter as well as possible interventions to improve their participation. In addition, the COVID-19 pandemic has triggered unprecedented disruptions that impacted the CPD of healthcare professionals. Audiologists encountered unique challenges amidst the pandemic, necessitating swift adaptations and innovations in their CPD practices. While considerable literature has been published about the shift of education systems to online platforms during the pandemic, less is known about its impact on the CPD of young privatesector audiologists.
Methods
A descriptive, qualitative research approach was adopted, with semi-structured online interviews being conducted with 11 audiologists practicing in the private sector in KwaZulu-Natal Province, South Africa. Purposive sampling was employed followed by a snowball technique. The five concepts of Andragogy were used as a conceptual and analytical framework thereafter the study relied on deductive thematic analysis.
Results
The participants' CPD experiences aligned with the five key concepts of andragogy, including selfconcept, adult learning experiences, readiness to learn, orientation to learning, and internal motivation. Eight sub-themes emerged, reflecting aspects such as personal accountability, informal learning, educational requirements, interprofessional development, improved clinical skills, and the influence of fear of consequences. The study illuminated the dual impact of the COVID-19 pandemic on the CPD activities of young audiologists. While the pandemic introduced significant disruptions to traditional CPD modalities, it also spurred innovative adaptations, particularly the shift to online learning platforms. This shift led to positive changes such as increased flexibility, cost-effectiveness, and diverse learning opportunities. However, it also posed challenges, including isolation and networking issues, uncertain quality assurance, and limited interactivity. Three primary barriers to CPD participation were identified: 1) personal, 2) financial, and 3) structural. These barriers highlighted the multifaceted challenges that audiologists encounter in maintaining and enhancing their professional competencies. Participants also provided valuable recommendations for overcoming these barriers, emphasizing the need for more flexible, accessible, and supportive CPD structures that cater to the specific needs of audiologists in the private sector.
Conclusion
Statutory bodies need to draw on the experiences of young audiologists during the planning and implementation of CPD for it to be effective and purposeful. The COVID-19 pandemic had a lasting impact on the CPD journeys of young audiologists in the private sector. While presenting formidable challenges, including disrupting traditional learning modalities, the pandemic also catalyzed innovations and adaptations within the profession through the predominance of online learning. Understanding their experiences and implementing strategies to address the barriers will enable the active engagement of private sector audiologists in their continued education.
The prevelance of chronic kidney disease in South Africa comparison with Sub-Saharan Africa and globally.
(2023) Hariparshad, Sudesh Premchund.; Assounga, Alain Guy Honore.
Chronic kidney disease (CKD) represents a significant global public health challenge as one of the most prevalent non-communicable diseases and a leading cause of mortality worldwide. Amidst the pandemic of non-communicable diseases, CKD's gradual progression often eludes recognition, necessitating a robust understanding of its prevalence and patterns to guide interventions. There is no direct comparison of CKD prevalence between South Africa, Africa, and the global landscape in the available literature. This study sought to bridge this gap by systematically comparing CKD prevalence rates across these geographical regions while investigating the underlying reasons for observed differences. A comprehensive literature search compared CKD prevalence in South Africa with sub-Saharan, African, and global studies. The review was registered with the International Prospective Register of Systematic Reviews (PROSPERO), with multiple search engines being used. The findings culminated in the publication of an original paper titled "The Prevalence of CKD in South Africa - Limitations of Comparative Studies with Sub-Saharan Africa, Africa, and Global Data" in the Biomedical Central Nephrology Journal on March 21, 2023. The research revealed statistically significant differences in CKD prevalence rates among the studied regions. However, these differences stemmed predominantly from substantial variations in sample sizes rather than actual disparities in prevalence rates. The systematic review illuminated a spectrum of factors contributing to this variability, including divergent definitions of CKD, lack of assessment for chronicity, variations in serum creatinine calculations, disparities in formulas used to estimate glomerular filtration rate (eGFR), demographic distinctions, and differences in risk factors associated with CKD development. This study underscores the need for a nuanced understanding of CKD prevalence and its determinants to inform targeted interventions in addressing this global health challenge.
Sexually Transmitted Infections among men who have sex with men in the Durban area, South Africa.
(2024) Mofolorunsho, Kehinde Charles.; Abbai, Nathlee Samantha.; Ojo, Abidemi.
Introduction: Gonorrhoea and chlamydia are amongst the most common sexually transmitted infections (STIs) worldwide, constituting a major public health problem. The incidence and prevalence of these infections are widespread, particularly in resource-poor countries due to the lack of access to health care facilities and ineffective diagnostic methods. In the African region, gonorrhoea and chlamydia have been reported to account for 11.4 and 12 million new cases per year, respectively. Gonorrhoea which is caused by the bacterium, Neisseria gonorrhoeae, and chlamydia, caused by the bacterium Chlamydia trachomatis have been found to be associated with serious health complications including infertility, pelvic inflammatory disease (PID), and epididymitis. Infections caused by these pathogens significantly increases the risk of Human Immunodeficiency Virus (HIV) transmission, particularly in men who have sex with men (MSM). Most MSM are asymptomatic, engaging in highrisk sexual behaviours, and have become an understudied group at greater risk for STI infections globally. C. trachomatis serovars have been linked to specific diseases, with serovars D-K detected in urogenital infections. In MSM, serovars reported were predominantly G, D and J. Microbiome variation has been found to be substantially affected by sexual practice. The bacterial composition of the male urinary microbiome is reported to influence the risk for the development of sexually transmitted infections. However, little is known about the urinary microbiome of MSM. The aim of this study was to determine the prevalence and risk factors associated with N. gonorrhoeae and C. trachomatis infections; characterize the distribution of C. trachomatis genotypes, and assess the bacterial composition of the urinary microbiome in a population of South African MSM.
Methods: This study which was in two parts, was conducted over a 3-year period. The first part involved a systematic review and meta-analysis on the prevalence of N. gonorrhoeae and C. trachomatis among MSM in sub-Saharan Africa while the second part involved a cross-sectional laboratory based study. This cross-sectional laboratory based study included sexually active MSM, 18 years and older, willing to provide written informed consent and a urine sample to test for N. gonorrhoeae and C. trachomatis infections. A total of 200 MSM from the King Edward VIII hospital and the Aurum Institute both in Durban, South Africa were enrolled into the study. Urine samples were provided by each participant, and 10ml of each urine sample was centrifuged and the recovered pellets subjected to further molecular analyses. With a commercially available kit, deoxyribonucleic acid (DNA) was extracted from the sample pellets following the manufacturer’s protocol for the isolation of genomic DNA. N. gonorrhoeae and C. trachomatis were detected using the Applied Biosystems™ TaqMan® Assays. Amplification was performed on the QuantStudio 5 Real-time polymerase chain reaction (PCR) detection system. In addition, molecular genotyping of C. trachomatis positive samples was performed by an omp1 gene semi-nested PCR followed by restriction fragment length polymorphism (RFLP) analysis. The amplified product was digested with AluI, DdeI and HinfI restriction enzymes. Banding patterns obtained after digestion were used to determine the genotypes. The urinary microbiomes of study participants were characterized using 16S rRNA (V3 and V4) gene sequencing on the Illumina MiSeq platform. Participants’ demographics, sexual history, associated risk factors for each of the STIs as well as the barriers and facilitators to care were documented. All analyses were conducted using STATA 17.1 as well as the RStudio version 3.6.3 software.
Results: The overall result of the meta-analysis gave a pooled prevalence of 27% (95% CI, 19–39%), with an I2 of 98% which indicates high heterogeneity amongst the studies. Subgroup analysis by country indicated that South Africa (n = 6) has a prevalence of 38%. Findings from our study showed that the prevalence of N. gonorrhoeae and C. trachomatis were 3.0% and 6.0%, respectively. Younger age was significantly associated with testing positive for C. trachomatis (p=0.037). Other factors significantly associated with testing positive for C. trachomatis included, education level, partner having other partners, sex practices, condom use and circumcision status (p<0.05). Being between the ages of 30-39 years old reduced the risk of acquiring C. trachomatis infection (OR: 0.10, 95% CI: 0.0120-0.7564, p=0.026). In addition, being circumcised reduced the risk of contracting C. trachomatis (adjusted OR: 0.01, 95% CI: 0.0005-0.3516, p=0.01). However, having between 2-4 sex partners increased the risk of testing positive for C. trachomatis (adjusted OR: 107.45, 95% CI: 1.3467- 8573.3130, p=0.036). Cohabiting with one’s sex partner, engaging in group sex, and drug use were significantly associated (p<0.05) with testing positive for N. gonorrhoeae infection. Fear and stigma were the main barriers to accessing health care in the studied population. The genotyping assays showed that genotype E was the most prevalent genotype present in 60% of the men infected with C. trachomatis. Other genotypes detected were Genotype I (30%) and Genotype J (10%). According to the bacterial taxonomic analysis, Prevotella and Lactobacillus were detected in urine samples of MSM. Alpha diversity metrics showed a slight increase in microbial diversity in positive samples. This was however not significant (ANOVA, P > 0.05). Principal coordinates analysis (PCoA) showed that the microbiome of C. trachomatis infected MSM was not clearly separated from those uninfected. Using normalized unweighted UniFrac dissimilarities, distinct bacterial communities were not detected between positive and negative samples (PERMANOVA F1,22= 1.0284, R2=0.047%, P=0.385).
Conclusion: This study showed that C. trachomatis was prevalent in the study population and this finding was confirmed by previous studies conducted among MSM in South Africa. A proportion of the population who tested positive for both STIs were asymptomatic. In addition, finding from our review suggests that the burden of N. gonorrhoeae and C. trachomatis among MSM in South Africa and the rest of sub-Saharan Africa is higher when compared with other regions. These highlights the need for routine screening of these infections among MSM in order to facilitate proper management since some MSM engage in risky sexual behaviour. Genotyping, using the PCR-RFLP technique revealed the presence of three genotypes circulating in the study population. An important finding was the detection of genotype I. Since this genotype is common among women and heterosexual men, further research is needed to provide clarity as to why this genotype was present among MSM. The microbial composition of urine samples from our study participants showed diverse bacterial communities including Gardnerella and Sneathia which are associated with bacterial vaginosis in women. Therefore, more studies on the role of the female urinary microbiota in relation to MSM urinary health, needs to be conducted. This study adds to the growing body of literature on genitourinaryinfections in South African MSM and provides data that serves as a baseline for future research.
Co-Operatives in South Africa: Advancing Solidarity Economy Pathways from Below
(University of KwaZulu-Natal Press, 2019) Satgar, Vishwas.
Co-operatives in post-apartheid South Africa have featured in the Reconstruction and Development Programme, legislation, vertical and horizontal state policy and various discourses from Black Economic Empowerment, ‘two economies’ and ‘radical economic transformation’. In practice, the big push by government through quantitative growth, seed capital and top-down movement building has not yielded viable, member-driven and values-centred co-operatives leading systemic change. Government looks to the experience of Afrikaner nationalism for keys to success, while some co-operative development programmes are breaking new ground in co-operative banking and community public works programmes. Yet, government co-operative pathways are facing serious limits. At the same time, solidarity economy practitioners have been fostering pathways from below, both actual and potential, within various co-operative experiences. Solidarity economy practice is not seeking government validation nor demanding recognition through adoption. Instead, solidarity economy forces are seeking to work with, against and beyond the state to build institutionalised and decolonised solidarity relations in a society increasingly grounded in market values of individualism, competition and greed. This volume builds on a previous collection, The Solidarity Economy Alternative: Emerging Theory and Practice (2014), and inaugurates a debate between leading government co-operative development practitioners and its critics, many of whom are working to advance bottom-up solidarity economy pathways.