Department of Biochemistry, Cell and Molecular Biology

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    Co-infections of SARS-CoV-2 with respiratory syncytial virus and human influenza A in patients with symptoms of COVID-19 in Ghana: A retrospective study
    (New Microbes and New Infections, 2024-08-19) Duedu, O.K.; Gyamfi, J.; Ayivor-Djanie, R.; Afenya, G.; Agbuglah, B.I.; Agbogli, K.H.; Essandoh, P.; Kugbemanya, S.; Adiku, K.T.
    Background: During the COVID-19 pandemic the aetiology of respiratory illnesses were narrowed to SARS-CoV-2. This prevented diagnosis of other pathogens and patients were not notified of the accurate diagnosis of their illnesses when SARS-CoV-2 was absent. It is therefore important to look back and determine what else was present but was missed. Objective: This retrospective study sought to gain insights into prevalence of respiratory syncytial virus (RSV) and influenza A alongside SARS-CoV-2 in patients who reported with clinical symptoms of respiratory illnesses. Methods: Samples from patients who had reported of respiratory symptoms were selected at random from a pool. RNA was extracted and RT-PCR was performed for SARS-CoV-2, RSV and Influenza A in parallel. Data on the clinical symptoms was extracted from case-base forms and analysed. Results: Of the 400 symptomatic samples tested, prevalence of SARS-CoV-2, influenza A and RSV was 20.3 %, 2.0 % and 0.5 % respectively. Only one sample tested positive for SARS-CoV-2 and influenza A. About 77 % of the symptomatic cases did not test positive for any of the three agents. Cough (79 %) was the most common symptom followed by fever and chills, headache, sore throat and runny nose. Conclusion: The large proportion of symptomatic cases that tested negative for all three respiratory viruses raises a flag and a need for more investigations into the actual burden of respiratory aetiologic agents during the pandemic. With the low levels of co-infections, parallel testing may not be needed however, a strong case for multiplex tests for respiratory agents exists.
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    Assessment of bacterial diversity in western Accra, Ghana, drinking water samples
    (Journal of Water, Sanitation and Hygiene for Development, 2019) Ecklu-Mensah, G.; Sackey, S.T.; Morrison, H.G.; et.al
    The design and performance characteristics of municipal drinking water systems can profoundly influence public health. To assess the operational attributes of an Accra, Ghana drinking water distribution system, high-throughput 454 pyrosequencing was employed to characterize its bacterial community composition. Samples from the waterworks and four household sources (one household tap and three polytank storage units) were analyzed within one of Accra’s distribution networks over 4 months. Samples provided between 9,059 and 20,076 reads (average ¼ 13,056) that represented a broad range of bacterial diversity, including rare genera. Minimum Entropy Decomposition (MED) analysis showed that the sequences described four major assemblages. Assemblages 1 and 2 dominated the waterworks and household tap samples while polytank storage unit samples, with one exception, contained assemblages 3 or 4. The considerable bacterial taxonomic difference between different sources suggests that contamination and/or selective growth shapes bacterial community structures after treatment at the waterworks. Of particular interest are the major differences between the poly tank samples following storage and the tap/waterworks samples, suggesting that water storage (stagnation) can select for unique microbial populations
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    Molecular Identification and Characterization of Five Ganoderma Species from the Lower Volta River Basin of Ghana Based on Nuclear Ribosomal DNA (nrDNA) Sequences
    (Journal of Fungi, 2024) Anang, A. K.; Gbewonyo, W. S. K.; Quarcoo, A.; et al
    Ganoderma is a genus of biomedical fungus that is used in the development of numerous health products throughout the world. The Lower Volta River Basin of Ghana is an undulating land surface covered by extensive vegetation and water bodies and is rich in polypore mushrooms resembling various members of the Ganoderma genus. Despite the extensive biopharmaceutical benefits of Ganoderma spp., the isolates from the Lower Volta River Basin have not been properly characterized, thus limiting their use in the development of biotechnological products. In this study, Ganoderma spp. collected from the Lower Volta River Basin were genetically analyzed using the nuclear ribosomal sequences, the internal transcribed spacer 2 (ITS 2), the complete internal transcribed spacer (ITS), and the nuclear large subunit (nLSU). Blastn search and sequence analysis revealed that the sample we coded as Ganoderma LVRB-2 belongs to G. mbrekobenum, whereas Ganoderma LVRB-1, Ganoderma LVRB-14, and Ganoderma LVRB-16 belong to the species G. enigmaticum. Our analysis further demonstrates that Ganoderma LVRB-17 belongs to the species G. resinaceum. Thus, the five samples collected in the present study were positioned in three different distinct groups, namely G. mbrekobenum, G. enigmaticum, and G. resinaceum. The current data may serve as reference points for future studies.
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    Molecular epidemiology and current management of Infectious Spleen and Kidney Necrosis Virus (ISKNV) infection in Ghanaian cultured tilapia
    (Aquaculture, 2024) Ayiku, A.N.A.; Adelani, A.A.; Duodu, S.; et al.
    Infectious Spleen and Kidney Necrosis Virus (ISKNV) is globally gaining more attention, due to its highly sig nificant economic impact on the aquaculture industry. In late 2018, unusually high levels of mortality (60–90%) was reported in some intensive tilapia cage culture systems on the Eastern bank of Lake Volta in Ghana. This resulted in the fold-up of several small and medium scale farms. Preliminary investigations confirmed the involvement of ISKNV, a viral pathogen noted for fatal systemic infections in many fish species. As a follow-up on the outbreak situation, and post-mass vaccination of affected fish farms, the need to investigate further the molecular epidemiology and phylogeography of the virus across Lake Volta became paramount. A multiplexed PCR assay to detect the virus and MinION™ nanopore sequencing of the Major Capsid Protein (MCP) were performed to investigate the presence and genotype of ISKNV in tilapia collected from 30 randomly selected farms at various geographical locations. ISKNV was found to be widely distributed across the lake and detected in 80% of farms with a reported average daily mortality of 40%. Fry and juvenile fish were the most affected, and approximately 50% of fish that tested positive were asymptomatic. These apparently healthy fish are likely contributors of virus transmission across farms. Phylogenetic analysis of the MCP revealed that all 35 isolates from 14 different farms distributed across the lake clustered with ISKNV clade I with 100% homology to isolates from the 2019 outbreak strain. Vaccination and heat-shock treatment; the two main specific interventions currently employed to control the viral pathogen have not achieved much success, and ISKNV remains a threat to the growth of the aquaculture industry in Ghana. The outcome of this study can be useful in improving fish health management and biosecurity policies in the aquaculture industry.
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    In Silico Identification of a Potential TNF-Alpha Binder Using a Structural Similarity: A Potential Drug Repurposing Approach to the Management of Alzheimer’s Disease
    (BioMed Research International, 2024) Tettevi, E.J.; Ocloo, A.; Kuevi, D.N.O.; et al.
    Alzheimer’s disease (AD) is a neurodegenerative disorder with no conclusive remedy. Yohimbine, found in Rauwolfia vomitoria may reduce brain inflammation by targeting tumour necrosis factor-alpha (TNFα), implicated in AD pathogenesis. Metoserpate, a synthetic compound, may inhibit TNFα. The study is aimed at assessing the potential utility of repurposing metoserpate for TNFα inhibition to reduce neuronal damage and inflammation in AD. The development of safe and effective treatments for AD is crucial to addressing the growing burden of the disease, which is projected to double over the next two decades. Methods. Our study repurposed an FDA-approved drug as TNFα inhibitor for AD management using structural similarity studies, molecular docking, and molecular dynamics simulations. Yohimbine was used as a reference compound. Molecular docking used SeeSAR, and molecular dynamics simulation used GROMACS. Results. Metoserpate was selected from 10 compounds similar to yohimbine based on pharmacokinetic properties and FDA approval status. Molecular Docking and simulation studies showed a stable interaction between metoserpate and TNFα over 100 ns (100000 ps). This suggests a reliable and robust interaction between the protein and ligand, supporting the potential utility of repurposing metoserpate for TNFα inhibition in AD treatment. Conclusion. Our study has identified metoserpate, a previously FDA-approved antihypertensive agent, as a promising candidate for inhibiting TNFα in the management of A
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    Pseudogenomic Insights Into The Evolution Of Mycobacterium Ulcerans
    (BMC Genomics, 2024) Kyei-Baffour, E.S.; Owusu-Boateng, K.; Isawumi, A.; et al.
    Background: Buruli ulcer (BU) disease, caused by Mycobacterium ulcerans (MU) and characterized by necrotic ulcers is still a health problem in Africa and Australia. The genome of the bacterium has several pseudogenes due to recent evolutionary events and environmental pressures. Pseudogenes are genetic elements regarded as non-essential in bacteria, however, are less studied due to limited available tools to provide understanding of their evolution and roles in MU pathogenicity. Results This study developed a bioinformatic pipeline to profile the pseudogenomes of sequenced MU clinical isolates from different countries. One hundred and seventy-two MU genomes analyzed revealed that The pseudogenomes of African strains corresponded to the two African lineages 1 and 2. Pseudogenomes were lineages and location-specific, and African lineage 1 was further divided into A and B. Lineage 2 had less relaxation in positive selection than lineage 1, which may signify different evolutionary points. Based on the Gil-Latorre model, African strains may be in the latter stages of evolutionary adaptation and are adapting to an environment rich in metabolic resources with a lower temperature and decreased UV radiation. The environment fosters oxidative metabolism and MU may be less reliant on some secondary metabolites. In-house pseudogenomes from Ghana and Cote d’Ivoire were different from other African strains; however, they were identified as African strains. Conclusion Our bioinformatic pipeline provides pseudogenomic insights to complement other whole genome analyses, providing a better view of the evolution of the genome of MU and suggesting an adaptation model which is important in understanding transmission. MU pseudogene profiles vary based on lineage and country, and an apparent reduction in insertion sequences used for the detection of MU, which may adversely affect the sensitivity of diagnosis. Significance Prevention and treatment of Buruli ulcer is still a problem but large whole genome datasets on M. ulcerans are readily available. However, genomic studies fail to thoroughly investigate pseudogenes to probe evolutionary changes in the bacteria, and this can be attributed to the lack of bioinformatic tools. This work studied pseudogenes in Mycobacterium ulcerans (MU) to understand its adapted niche and evolutionary differences across African strains. Our results suggest that an MU niche-adapted model is important in understanding transmission. Also, MU pseudogene profiles vary based on lineage and country, suggesting their influence on pseudogenization patterns
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    Pseudogenomic Insights Into The Evolution Of Mycobacterium Ulcerans
    (BMC Genomics, 2024) Kyei-Baffour, E.S.; Owusu-Boateng, K.; Isawumi, A.; et al.
    Background: Buruli ulcer (BU) disease, caused by Mycobacterium ulcerans (MU) and characterized by necrotic ulcers is still a health problem in Africa and Australia. The genome of the bacterium has several pseudogenes due to recent evolutionary events and environmental pressures. Pseudogenes are genetic elements regarded as non-essential in bacteria, however, are less studied due to limited available tools to provide understanding of their evolution and roles in MU pathogenicity. Results This study developed a bioinformatic pipeline to profile the pseudogenomes of sequenced MU clinical isolates from different countries. One hundred and seventy-two MU genomes analyzed revealed that The pseudogenomes of African strains corresponded to the two African lineages 1 and 2. Pseudogenomes were lineages and location-specific, and African lineage 1 was further divided into A and B. Lineage 2 had less relaxation in positive selection than lineage 1, which may signify different evolutionary points. Based on the Gil-Latorre model, African strains may be in the latter stages of evolutionary adaptation and are adapting to an environment rich in metabolic resources with a lower temperature and decreased UV radiation. The environment fosters oxidative metabolism and MU may be less reliant on some secondary metabolites. In-house pseudogenomes from Ghana and Cote d’Ivoire were different from other African strains; however, they were identified as African strains. Conclusion Our bioinformatic pipeline provides pseudogenomic insights to complement other whole genome analyses, providing a better view of the evolution of the genome of MU and suggesting an adaptation model which is important in understanding transmission. MU pseudogene profiles vary based on lineage and country, and an apparent reduction in insertion sequences used for the detection of MU, which may adversely affect the sensitivity of diagnosis. Significance Prevention and treatment of Buruli ulcer is still a problem but large whole genome datasets on M. ulcerans are readily available. However, genomic studies fail to thoroughly investigate pseudogenes to probe evolutionary changes in the bacteria, and this can be attributed to the lack of bioinformatic tools. This work studied pseudogenes in Mycobacterium ulcerans (MU) to understand its adapted niche and evolutionary differences across African strains. Our results suggest that an MU niche-adapted model is important in understanding transmission. Also, MU pseudogene profiles vary based on lineage and country, suggesting their influence on pseudogenization patterns
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    In Silico Identification Of A Potential TNF-Alpha Binder Using A Structural Similarity: A Potential Drug Repurposing Approach To The Management Of Alzheimer’s Disease
    (BioMed Research International, 2023) Tettevi, E.J.; Ocloo, A.; Kuevi, D.N.O.; et al.
    Alzheimer’s disease (AD) is a neurodegenerative disorder with no conclusive remedy. Yohimbine, found in Rauwolfia vomitoria may reduce brain inflammation by targeting tumour necrosis factor-alpha (TNFα), implicated in AD pathogenesis. Metoserpate, a synthetic compound, may inhibit TNFα. The study is aimed at assessing the potential utility of repurposing metoserpate for TNFα inhibition to reduce neuronal damage and inflammation in AD. The development of safe and effective treatments for AD is crucial to addressing the growing burden of the disease, which is projected to double over the next two decades. Methods. Our study repurposed an FDA-approved drug as TNFα inhibitor for AD management using structural similarity studies, molecular docking, and molecular dynamics simulations. Yohimbine was used as a reference compound. Molecular docking used SeeSAR, and molecular dynamics simulation used GROMACS. Results. Metoserpate was selected from 10 compounds similar to yohimbine based on pharmacokinetic properties and FDA approval status. Molecular Docking and simulation studies showed a stable interaction between metoserpate and TNFα over 100 ns (100000 ps). This suggests a reliable and robust interaction between the protein and ligand, supporting the potential utility of repurposing metoserpate for TNFα inhibition in AD treatment. Conclusion. Our study has identified metoserpate, a previously FDA-approved antihypertensive agent, as a promising candidate for inhibiting TNFα in the management of AD.
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    he global transcriptome of Plasmodium falciparum mid stage gametocytes (stages II–IV) appears largely conserved and gametocyte-specific gene expression patterns vary in clinical isolates
    (American Society for Microbiology, 2023) Kengne-Ouafo, J.A.; Bah, S.Y.; Kemp, A.; et al.
    Our overall understanding of the developmental biology of malaria Parasites have been greatly enhanced by recent advances in transcriptomic analysis. However, most of these investigations rely on laboratory strains (LS) that were adopted into in vitro culture many years ago and the transcriptomes of clinical isolates (CI) circulating in human populations have not been assessed. In this study, RNA-seq was used to compare the global transcriptome of mid-stage gametocytes derived from three short-term cultured CI, with gametocytes derived from the NF54 reference laboratory strain. The core transcriptome appeared to be consistent between CI and LS-derived gametocyte preparations, but some important differences were also observed. A majority of gametocyte-specific genes (43/53) appear to have relatively higher expression in CI-derived gametocytes than in LS-derived gametocytes, but a K-means clustering analysis showed that genes involved in flagellum- and microtubule-based processes (movement and motility) were more abundant in both groups, albeit with some differences between them. In addition, gametocytes from one CI described as CI group II gametocytes (CI:GGII) showed gene expression variation in the form of reduced gametocyte-specific gene expression compared to the other two CI-derived gametocytes (CI gametocyte group I, CI:GGI), although the mixed developmental stages used in our study is a potential confounder, only partially mitigated by the inclusion of of multiple replicates for each CI. Overall, our study suggests that there may be subtle differences in the gene expression profiles of mid-stage gametocytes from CI relative to the NF54 reference strain of Plasmodium falciparum. Thus, it is necessary to deploy gametocyte-producing clinical parasite isolates to fully understand the diversity of gene expression strategies that may occur during the sequestered development of parasite sexual stages.
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    Lessons from the pandemic: new best practices in selecting molecular diagnostics for point-of-care testing of infectious diseases in sub-Saharan Africa
    (Expert Review of Molecular Diagnostics, 2023) Baldeh, M.; Bawa, F.K.; Bawah, F.U.; et al.
    Introduction: Point-of-care molecular diagnostics offer solutions to the limited diagnostic availability and accessibility in resource-limited settings. During the COVID-19 pandemic, molecular diagnostics became essential tools for accurate detection and monitoring of SARS-CoV-2. The unprecedented demand for molecular diagnostics presented challenges and catalyzed innovations which may provide lessons for the future selection of point-of-care molecular diagnostics. Areas Covered: We searched PubMed from January 2020 to August 2023 to identify lessons learned from the COVID-19 pandemic, which may impact the selection of point-of-care molecular diagnostics for future use in sub-Saharan Africa. We evaluated this in the context of REASSURED criteria (Real-time connectivity; Ease of specimen collection; Affordable; Sensitive; Specific; User-friendly; Rapid and robust; equipment-free; and deliverable to users at the point of need) for point-of-care diagnostics in resource-limited settings. Expert Opinion: The diagnostic challenges and successes during the COVID-19 pandemic affirmed the importance of the REASSURED criteria but demonstrated that these are not sufficient to ensure new Diagnostics will be appropriate for public health emergencies. Capacity for rapid scale-up of diagnostic Testing and transferability of assays, data, and technology are also important, resulting in updated REST-ASSURED criteria. Few diagnostics will meet all criteria, and trade-offs between criteria will need to be context-specific.