• Investigating the role of calcium ion in reducing Enterobacter cloacae carbapenem resistance
• Supervisor(s): Abiola Isawumi
• Contact details: isawumiabiola@gmail.com

Summary of Hosting Lab

Our group is investigating the antimicrobial resistance (AMR) mechanisms of novel superbugs (ESKAPE pathogens) and newly emerging Pan-African multidrug-resistant (MDR) pathogens prevalent and diversely distributed in hospital environments, especially those that are implicated in nosocomial infections in the Intensive Care Unit. We are advancing research efforts in hetero-resistance mechanisms, bacterial virulence and pathogenesis, lipopolysaccharide modifications, biofilm-motility interplay in bacterial resistance, toxin-antitoxin, and secretory systems. As we leverage phenotypic algorithms and molecular tools for developing diverse assays to potentiate antibiotic effectiveness and understand opportunistic pathogen antibiotic-evasion pathways, we are also taking advantage of nanoparticles for antibiotic delivery and phage technology to intercept AMR pathways to inform treatment strategies.

Project Description

Our previous study showed that calcium ions potentiated carbapenems against MDR Enterobacter cloacae (EC) with a 50% reduction in the levels of resistance1. However, the mechanisms by which this is achieved are unclear. We posit that Ca2+ outcompetes EC lipopolysaccharides and deactivates efflux porters to reduce carbapenem resistance. This project will contribute to the fight against AMR and provide relevant therapeutic insights to inform treatment strategies.

Publications

Isawumi A, Abban MK, Ayerakwa EA, Mosi L. Calcium Potentiated Carbapenem Effectiveness Against Resistant Enterobacter Species. Microbiology Insights. 2022;15. doi:10.1177/11786361221133728

Isawumi A, Ayerakwa EA, Abban MK, Mosi L. Expression profiles of sporulation genes in multidrug-resistant Bacillus species isolated from intensive care units of Ghanaian hospital. Experimental Biology and Medicine. 2023;248(6):501-507. doi:10.1177/15353702231160336

Molly Kukua Abban, Eunice Ampadubea Ayerakwa, Lydia Mosi, Abiola Isawumi. The burden of hospital acquired infections and antimicrobial resistance, Heliyon, 2023, e20561, ISSN 2405-8440, https://doi.org/10.1016/j.heliyon.2023.e20561

Abban RL, Kwabena S, Duodu S, Mosi L, Abiola Isawumi (2023) Targeting Proteus mirabilis BAM Complex Proteins for Development of Novel Antibiotics. Research Ideas and Outcomes 9: e106849. https://doi.org/10.3897/rio.9.e106849

A. Isawumi, A. Kukua Abban, A. Duodu, A. Mosi, M. Valvano (2020). Klebsiella oxytoca: Evolving superbug from Ghanaian Hospitals. International Journal of Infectious Diseases, 101(1):43-44. https://doi.org/10.1016/j.ijid.2020.09.147.

Major Lab techniques

Microbiology, Sample processing, Bacterial culturing and characterization, cell culturing, drug-assays development, secretory and tracking assays, cell culturing, virulence and infection assays, microscopy, nanoparticle synthesis set up, molecular biology assays, gene expression analysis, LPS profiling, phage isolation, collaborative research, documentation and reporting, mentoring, data curation and analysis

• Thematic field of study: Structural and biophysical characterization of proteins implicated in malaria and Buruli ulcer etiology
• Supervisor(s): Jerry Joe Harrison
• Contact details: jjharrison@ug.edu.gh

Summary of Hosting Lab

Structural biology tools provide unique avenues for providing structural and functional information on macromolecules that are essential to the pathogenesis of diseases. My lab uses biophysical techniques such as X-ray crystallography and cryo-EM in studying macromolecular structures implicated in diseases and their complexes as well as with natural substrates and inhibitors to understand how these pathogens cause diseases. Our model organisms include HIV, SARS-CoV-2, Buruli Ulcer, and Malaria.

Project Description

Structural biology tools have been used extensively in understanding atomic level interactions of macromolecular entities thereby helping elucidate mechanisms that underlie diseases, drug discovery where structure guided drug design principles such as fragment-based drug discovery technologies have yielded therapies for diseases that had hitherto been refractory to conventional drug discovery methods. By using a combination of these tools, especially, X-ray crystallography, single particle cryo-electron microscopy (cryo-EM) and small angle X-ray scattering, we seek to provide 3D structural information for macromolecules and their complexes implicated in malaria and Buruli ulcer etiology to aid understanding of pathogenesis of diseases, elucidate the mechanism(s) of drug/inhibitor action, and to aid the discovery of new drugs against these diseases.

Publications

Yadav R, Courouble V.V, Dey S.K, Harrison J.J.E.K, Timm J, Hopkins J.B, Slack R.L, Sarafianos S.G, Ruiz F.X, Griffin P, Arnold E. Biochemical and structural insights into SARS-CoV-2 polyprotein processing by Mpro. Sci. Adv.8, eadd2191(2022). DOI:10.1126/sciadv.add2191.

Harrison, J.J.E.K., Passos D.O, Bruhn J.F, Bauman J.D, Tuberty L, DeStefano J.J, Ruiz F.X, Lyumkis D, Eddy Arnold (2021). Cryo-EM structure of the HIV-1 Pol polyprotein provides insights into virion maturation. Sci. Adv.8, eabn9874(2022). DOI:10.1126/sciadv.abn9874.

Courouble, V. V.; Dey, S. K.; Yadav, R.; Timm, J.; Harrison, J.J.E.K.; Ruiz, F. X.; Arnold, E.; Griffin, P. R. Revealing the Structural Plasticity of SARS-CoV-2 nsp7 and nsp8 Using Structural Proteomics. J. Am. Soc. Mass Spectrom. 2021, 32, 1618– 1630, DOI: 10.1021/jasms.1c00086.

Harrison, J.J.E.K.; Tuske, S.; Das, K.; Ruiz, F.X.; Bauman, J.D.; Boyer, P.L.; DeStefano, J.J.; Hughes, S.H.; Arnold, E. Crystal Structure of a Retroviral Polyprotein: Prototype Foamy Virus Protease
-Reverse Transcriptase (PR-RT). Viruses 2021, 13, 1495. https://doi.org/10.3390/v13081495.

Major Lab techniques

Cloning, protein expression and purification, X-ray crystallography, single particle cryo-EM

• Thematic field of study: Virus-Host interactions and their implications in pandemic virology
• Supervisor(s): Dr. Peter Kojo Quashie
• Contact details: pquashie@ug.edu.gh

Summary of Hosting Lab

We work at the intersection of virology, protein biochemistry, immunology and epidemiology with the aim to understand and therapeutically target key replicative and host:virus interaction processes in viruses of pandemic concern.

Project Description

The project on host-viral interactions and antiviral therapeutics.
Dr. Quashie’s group is studying the impact of endemic comorbidity on West African HIV responses. They lead the WACCBIP long-term HIV Infection CoHort Study, which involves recruiting, sampling, and characterizing HIV infection in 1000 newly diagnosed Ghanaians. Their research has also focused on the West African immune system’s response to SARS-Cov-2 infection and vaccination, and the role of endemic malaria.

Publications

Serwaa A, Oyawoye F, Owusu IA, Dosoo D, Manu AA, Sobo AK, Fosu K, Olwal CO, Quashie PK*, Aikins AR*. In vitro analysis suggests that SARS-CoV-2 infection differentially modulates cancer-like phenotypes and cytokine expression in colorectal and prostate cancer cells. Sci Rep. 2024 Oct 19;14(1):24625. doi: 10.1038/s41598-024-75718-1. PMID: 39427065; PMCID: PMC11490510.

Tapela K, Prah DA, Tetteh B, Nuokpem F, Dosoo D, Coker A, Kumi-Ansah F, Amoako E, Assah KO, Kilba C, Nyakoe N, Quansah D, Languon S, Anyigba CA, Ansah F, Agyeman S, Owusu IA, Schneider K, Ampofo WK, Mutungi JK, Amegatcher G, Aniweh Y, Awandare GA, Quashie PK*, Bediako Y*. Cellular immune response to SARS-CoV-2 and clinical presentation in individuals exposed to endemic malaria. Cell Rep. 2024 Aug 27;43(8):114533. doi: 10.1016/j.celrep.2024.114533. Epub 2024 Jul 24. PMID: 39052480; PMCID: PMC11372439

Manu AA, Owusu IA, Oyawoye FO, Languon S, Barikisu IA, Tawiah-Eshun S, Quaye O, Donkor KJ, Paemka L, Amegatcher GA, Denyoh PMD, Oduro-Mensah D, Awandare GA, Quashie PK. Development and utility of a SARS-CoV-2 pseudovirus assay for compound screening and antibody neutralization assays. Heliyon. 2024 May 19;10(10):e31392. doi: 10.1016/j.heliyon.2024.e31392. PMID: 38826759; PMCID: PMC11141373.

Olwal CO, Fabius JM, Zuliani-Alvarez L, Eckhardt M, Kyei GB, Quashie PK, Krogan NJ, Bouhaddou M, Bediako Y. Network modeling suggests HIV infection phenocopies PI3K-AKT pathway mutations to enhance HPV-associated cervical cancer. Molecular Omics. 2023 Aug 14;19(7):538-551. doi: 10.1039/d3mo00025g. PMID: 37204043.

Tapela K, Opurum PC, Nuokpem FY, Tetteh B, Siaw GK, Humbert MV, Tawiah-Eshun S, Barakisu AI, Asiedu K, Arhin SK, Manu AA, Appiedu-Addo SNA, Obbeng L, Quansah D, Languon S, Anyigba C, Dosoo D, Edu NKO, Oduro-Mensah D, Ampofo W, Tagoe E, Quaye O, Donkor IO, Akorli J, Aniweh Y, Christodoulides M, Mutungi J, Bediako Y, Rayner JC, Awandare GA, McCormick CJ, Quashie PK. Development of an Affordable ELISA Targeting the SARS-CoV-2 Nucleocapsid and Its Application to Samples from the Ongoing COVID-19 Epidemic in Ghana. Mol Diagn Ther. 2023 Sep;27(5):583-592. doi: 10.1007/s40291-023-00655-0. Epub 2023 Jul 18. PMID: 37462793; PMCID: PMC10435612.

Major Lab techniques

Mammalian Cell Culture, qRTPCR, Flow Cytometry, Sequencing, assay development

• Thematic field of study: Binding Inhibitory Activity of PFD1140w antibodies against clinical isolates
• Supervisor(s): Dr Henrietta Mensah-Brown, Prof Gordon Awandare
• Contact details: hemensah-brown@ug.edu.gh

Summary of Hosting Lab

The Mensah-Brown lab at WACCBIP, University of Ghana works on malaria parasite biology and immunology, focused on parasite invasion strategies as well as the identification and validation of potential targets for drug and vaccine development. This is particularly important since malaria remains a major global health challenge. The recent resurgence in malaria morbidity and mortality signals the need to identify and develop drugs and vaccines that can aid the elimination of malaria.

Project Description

PFD1140w is a gene which has been shown to upregulated with var2CSA in placental malaria parasites. In our recent studies, we found that PFD1140w transcripts were similarly upregulated with var2CSA in parasites from children with severe malaria compared to parasites from children with uncomplicated malaria. Our unpublished data further showed that anti-PFD1140w antibody levels in children with severe were significantly elevated when compared to children with uncomplicated malaria, while anti-PFD1140w antibodies used in combination with anti-var2CSA antibodies showed the ability to disrupt parasite binding to CSA in a limited number of laboratory parasites.
In this project, we will expand our studies to clinical isolates and more laboratory lines to confirm the binding inhibitory activity of these parasites

Publications

Francis SE, Malkov VA, Oleinikov AV, Rossnagle E, Wendler JP, Mutabingwa TK, Fried M, Duffy PE. Six genes are preferentially transcribed by the circulating and sequestered forms of Plasmodium falciparum parasites that infect pregnant women. Infect Immun. 2007 Oct;75(10):4838-50. doi: 10.1128/IAI.00635-07. Epub 2007 Aug 13. PMID: 17698567; PMCID: PMC2044550.

Kumar V, Kaur J, Singh AP, Singh V, Bisht A, Panda JJ, Mishra PC, Hora R. PHISTc protein family members localize to different subcellular organelles and bind Plasmodium falciparum major virulence factor PfEMP-1. FEBS J. 2018 Jan;285(2):294-312. doi: 10.1111/febs.14340. Epub 2017 Dec 10. PMID: 29155505.

Fried M, Duffy PE. Analysis of CSA-binding parasites and antiadhesion antibodies. Methods Mol Med. 2002;72:555-60. doi: 10.1385/1-59259-271-6:555. PMID: 12125153.

Major Lab techniques

Sample processing, parasite culture, ELISA, Drug assays, Flow cytometry