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2. Minimal domain peptides derived from enterocins exhibit potent antifungal activity.

Author

Cohen, Dorrian G., Heidenreich, Theresa M., Schorey, Jason W., Ross, Jessica N., Hammers, Daniel E., Vu, Henry M., Moran, Thomas E., Winski, Christopher J., Stuckey, Peter V., Ross, Robbi L., Yee, Elizabeth Arsenault, Santiago-Tirado, Felipe H., and Lee, Shaun W.

Subjects
ANTIMICROBIAL peptides, PEPTIDOMIMETICS, PEPTIDES, CRYPTOCOCCUS neoformans, MYCOSES, CANDIDA
Abstract

The antimicrobial peptide (AMP) circularized bacteriocin enterocin AS-48 produced by Enterococcus sp. exhibits broad-spectrum antibacterial activity via dimer insertion into the plasma membrane to form membrane pore structures, compromising membrane integrity and leading to bactericidal activity. A specific alpha-helical region of enterocin AS-48 has been shown to be responsible for the membrane-penetrating activity of the peptide. The canon syn-enterocin peptide library, generated using rational design techniques to have ninety-five synthetic peptide variants from the truncated, linearized, membrane-interacting domain of enterocin AS-48, was screened against three clinically relevant fungal strains: Cryptococcus neoformans , Candida albicans , and Candida auris for potential antifungal activity. Twelve peptides exhibited antifungal activity against C. neoformans , and two peptides exhibited activity against C. albicans. The fourteen active antifungal peptides were minimally cytotoxic to an immortalized human keratinocyte cell line (HaCats). Four select peptides were identified with minimum inhibitory concentrations (MICs) below 8 µM against C. neoformans. In 36-hour cell growth tests with these fungicidal peptides, fungicidal peptide no. 32 displayed inhibitory properties comparable to the leading antifungal medication fluconazole against C. neoformans. Screening of peptide no. 32 against a deletion library of C. neoformans mutants revealed that the mechanism of action of peptide no. 32 may relate to multivesicular bodies (MVBs) or polysaccharide capsule targeting. These findings importantly demonstrate that naturally derived AMPs produced by bacteria can be sourced, engineered, and modified to exhibit potent antifungal activity. Our results will contribute to the development of broad treatment alternatives to fungal infections and lend themselves to direct implications for possible treatment options for C. neoformans infections. [ABSTRACT FROM AUTHOR]

Published
2025
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3. The impact of home-based management of malaria on clinical outcomes in sub-Saharan African populations: a systematic review and meta-analysis

Author

Kua, Kok P., Lee, Shaun W. H., Chongmelaxme, Bunchai, Kua, Kok P., Lee, Shaun W. H., and Chongmelaxme, Bunchai

Abstract

Background Malaria remains a significant cause of morbidity and mortality globally and continues to disproportionately afflict the African population. We aimed to evaluate the effect of home management of malaria intervention on health outcomes. Methods In our systematic review and meta-analysis, six databases (Pubmed, Cochrane CENTRAL, EMBASE, CAB Abstracts and Global Health, CINAHL Complete, and BIOSIS) were searched for studies of home management of malaria from inception until November 15, 2023. We included before–after studies, observational studies, and randomised controlled trials of home management intervention delivered in community settings. The primary outcomes were malaria mortality and all-cause mortality. The risk of bias in individual observational studies was assessed using the ROBINS-I tool, whilst randomised controlled trials were judged using a revised Cochrane risk of bias tool and cluster-randomised controlled trials were evaluated using an adapted Cochrane risk of bias tool for cluster-randomised trials. We computed risk ratios with accompanying 95% confidence intervals for health-related outcomes reported in the studies and subsequently pooled the results by using a random-effects model (DerSimonian–Laird method). Results We identified 1203 citations through database and hand searches, from which 56 articles from 47 studies encompassing 234,002 participants were included in the systematic review. All studies were conducted in people living in sub-Saharan Africa and were rated to have a low or moderate risk of bias. Pooled analyses showed that mortality rates due to malaria (RR = 0.40, 95% CI = 0.29–0.54, P = 0.00001, I2 = 0%) and all-cause mortality rates (RR = 0.62, 95% CI = 0.53–0.72, P = 0.00001, I2 = 0%) were significantly lower among participants receiving home management intervention compared to the control group. However, in children under 5 years of age, there was no significant difference in mortality rates before and after implementa

Published
2024

5. Group AStreptococcusremains viable inside fibrin clots and gains access to human plasminogen for subsequent fibrinolysis and dissemination

Author

Vu, Henry M., primary, Liang, Zhong, additional, Bao, Yun-Juan, additional, Carles, Paulina G., additional, Keane, Jessica C., additional, Cerney, Madelyn G., additional, Dahnke, Caitlyn N., additional, Flores-Mireles, Ana L., additional, Ploplis, Victoria A., additional, Castellino, Francis J., additional, and Lee, Shaun W., additional

Published
2023
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11. Relationships Between Plasminogen-Binding M-Protein and Surface Enolase for Human Plasminogen Acquisition and Activation in Streptococcus pyogenes

Author

Ayinuola, Yetunde A., primary, Tjia-Fleck, Sheiny, additional, Readnour, Bradley M., additional, Liang, Zhong, additional, Ayinuola, Olawole, additional, Paul, Lake N., additional, Lee, Shaun W., additional, Fischetti, Vincent A., additional, Ploplis, Victoria A., additional, and Castellino, Francis J., additional

Published
2022
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12. Issues of Ageing in Malaysia: A Compilation of Research Findings

Author

Paraidathathu Thomas, Editor, Filzah Md Isa, Editor, Paraidathathu Thomas, Editor, and Filzah Md Isa, Editor

Subjects
Population aging--Malaysia
Abstract

This book aims to open up discussion of research findings on ageing issues in Malaysia. The increasing ageing population is an issue across all nations. In due time, there will be more older adults as compared to children. Based on calculations made by the consulting group Deloitte, 60 per cent of Asia's population will be 65 years and above by 2030. The Department of Statistics Malaysia has projected that by 2040, the percentage of the elderly in Malaysia will increase to 14.5 per cent. This book combines social, clinical, and health sciences, covering qualitative, quantitative, and mixed method approaches regarding potential business activities, health and financial well-being, and also clinical tests, solutions and proposals that will improve elderly health and care. So, this diverse scope of research will allow more readers, researchers, practitioners, policymakers, and the public to better grasp issues affecting the elderly. The findings will impact personal health and well-being, care service business, knowledge expansion, and application.

Published
2024

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