EDCTP Alumni Network

Fostering excellence and collaboration in the next generation of researchers

Call Career Development Fellowship (CDF)
Programme EDCTP2
Start Date 2020-11-01
End Date 2023-10-31
Project Code TMA2019CDF-2716
Status Active

Title

Determination of HIV-1 drug resistance among patients failing second-line treatment in Kenya using an in-house phenotypic assay (HIVDR)

Host Organisation

Institution Country
Kenya Medical Research Institute (KEMRI) Kenya

Current Organisation

Kenya Medical Research Institute

Current Job Title

Research Scientist

Education

Institution Degree Year
Nagasaki University, Japan PhD 2017-09-20
Nagasaki University, Japan MSc 2013-09-20
Kenyatta University, Kenya BSc 2011-07-01

Publications

Authors:
Date:
2013-10-01
Journal:
Drug Discoveries & Therapeutics
Content:
Identifiers:
Authors:
Date:
2020-12-20
Journal:
Scientific Reports
Content:
Abstract Echinocandins, including caspofungin, micafungin, and anidulafungin, are first-line antifungal agents for the treatment of invasive candidiasis. They exhibit fungicidal activity by inhibiting the synthesis of β-1,3-d-glucan, an essential component of the fungal cell wall. However, they are active only against proliferating fungal cells and unable to completely eradicate fungal cells even after a 24 h drug exposure in standard time-kill assays. Surprisingly, we found that caspofungin, when dissolved in low ionic solutions, had rapid and potent antimicrobial activities against multidrug-resistant (MDR) Candida and bacteria cells even in non-growth conditions. This effect was not observed in 0.9% NaCl or other ion-containing solutions and was not exerted by other echinocandins. Furthermore, caspofungin dissolved in low ionic solutions drastically reduced mature biofilm cells of MDR Candida auris in only 5 min, as well as Candida-bacterial polymicrobial biofilms in a catheter-lock therapy model. Caspofungin displayed ion concentration-dependent conformational changes and intracellular accumulation with increased reactive oxygen species production, indicating a novel mechanism of action in low ionic conditions. Importantly, caspofungin dissolved in 5% glucose water did not exhibit increased toxicity to human cells. This study facilitates the development of new therapeutic strategies in the management of catheter-related biofilm infections.
Identifiers:
Authors:
Date:
2020-08-05
Journal:
Pharmaceutical Sciences and Research
Content:
Identifiers:
Authors:
Date:
2018-04-01
Journal:
Journal of Medicinal Food
Content:
Identifiers:
Authors:
Satoshi Mizuta , author
Juliann Nzembi Makau , author
Ayako Kitagawa , author
Kanami Kitamura , author
Hiroki Otaki , author
Kodai Nishi , author
Ken Watanabe , author
Date:
2018-11-20
Journal:
ChemMedChem
Content:
Identifiers:
Authors:
Satoshi Mizuta , author
Juliann Nzembi Makau , author
Ayako Kitagawa , author
Kanami Kitamura , author
Hiroki Otaki , author
Kodai Nishi , author
Ken Watanabe , author
Date:
2018-11-20
Journal:
ChemMedChem
Content:
Identifiers:
Authors:
Date:
2020-03-19
Journal:
Viruses
Content:
The emergence of resistance to currently available anti-influenza drugs has heightened the need for antivirals with novel mechanisms of action. The influenza A virus (IAV) nucleoprotein (NP) is highly conserved and essential for the formation of viral ribonucleoprotein (vRNP), which serves as the template for replication and transcription. Recently, using in silico screening, we identified an antiviral compound designated NUD-1 (a 4-hydroxyquinolinone derivative) as a potential inhibitor of NP. In this study, we further analyzed the interaction between NUD-1 and NP and found that the compound interferes with the oligomerization of NP, which is required for vRNP formation, leading to the suppression of viral transcription, protein synthesis, and nuclear export of NP. We further assessed the selection of resistant variants by serially passaging a clinical isolate of the 2009 H1N1 pandemic influenza virus in the presence of NUD-1 or oseltamivir. NUD-1 did not select for resistant variants after nine passages, whereas oseltamivir selected for resistant variants after five passages. Our data demonstrate that NUD-1 interferes with the oligomerization of NP and less likely induces drug-resistant variants than oseltamivir; hence, it is a potential lead compound for the development of novel anti-influenza drugs.
Identifiers:
DOI: 10.3390/v12030337
Part of ISSN: 1999-4915

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