Alginate oligosaccharides enhance the antifungal activity of nystatin against candidal biofilms

Powell, Lydia; M., Jennifer Y.; Quoraishi, Sadik; Py, Charlène; Oger, Anaϊs; Gazze, Salvatore A.; Francis, Lewis; Ruhland, Christopher von; Owens, David; Rye, Philip D.; Hill, Katja E.; Pritchard, Manon F.; Thomas, David W.

doi:10.3389/fcimb.2023.1122340

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Alginate oligosaccharides enhance the antifungal activity of nystatin against candidal biofilms

Lydia Powell

, Jennifer Y. M. Adams, Sadik Quoraishi, Charlène Py, Anaϊs Oger, Salvatore A. Gazze, Lewis Francis

, Christopher von Ruhland, David Owens, Philip D. Rye, Katja E. Hill, Manon F. Pritchard, David W. Thomas

Frontiers in Cellular and Infection Microbiology, Volume: 13

Swansea University Authors: Lydia Powell , Lewis Francis

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© 2023 Powell, Adams, Quoraishi, Py, Oger, Gazze, Francis, von Ruhland, Owens, Rye, Hill, Pritchard and Thomas. This is an openaccess article distributed under the terms of the Creative Commons Attribution License (CC BY).
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DOI (Published version): 10.3389/fcimb.2023.1122340

Abstract

Background: The increasing prevalence of invasive fungal infections in immuno-compromised patients is a considerable cause of morbidity and mortality. With the rapid emergence of antifungal resistance and an inadequate pipeline of new therapies, novel treatment strategies are now urgently required.M...

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Published in:	Frontiers in Cellular and Infection Microbiology
ISSN:	2235-2988
Published:	Frontiers Media SA 2023
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URI:	https://cronfa.swan.ac.uk/Record/cronfa62485
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With the rapid emergence of antifungal resistance and an inadequate pipeline of new therapies, novel treatment strategies are now urgently required.Methods: The antifungal activity of the alginate oligosaccharide OligoG in conjunction with nystatin was tested against a range of Candida spp. (C. albicans, C. glabrata, C. parapsilosis, C. auris, C. tropicalis and C. dubliniensis), in both planktonic and biofilm assays, to determine its potential clinical utility to enhance the treatment of candidal infections. The effect of OligoG (0-6%) ± nystatin on Candida spp. was examined in minimum inhibitory concentration (MIC) and growth curve assays. Antifungal effects of OligoG and nystatin treatment on biofilm formation and disruption were characterized using confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM) and ATP cellular viability assays. Effects on the cell membrane were determined using permeability assays and transmission electron microscopy (TEM).Results: MIC and growth curve assays demonstrated the synergistic effects of OligoG (0-6%) with nystatin, resulting in an up to 32-fold reduction in MIC, and a significant reduction in the growth of C. parapsilosis and C. auris (minimum significant difference = 0.2 and 0.12 respectively). CLSM and SEM imaging demonstrated that the combination treatment of OligoG (4%) with nystatin (1 µg/ml) resulted in significant inhibition of candidal biofilm formation on glass and clinical grade silicone surfaces (p < 0.001), with increased cell death (p < 0.0001). The ATP biofilm disruption assay demonstrated a significant reduction in cell viability with OligoG (4%) alone and the combined OligoG/nystatin (MIC value) treatment (p < 0.04) for all Candida strains tested. TEM studies revealed the combined OligoG/nystatin treatment induced structural reorganization of the Candida cell membrane, with increased permeability when compared to the untreated control (p < 0.001).Conclusions: Antimicrobial synergy between OligoG and nystatin against Candida spp. highlights the potential utility of this combination therapy in the prevention and topical treatment of candidal biofilm infections, to overcome the inherent tolerance of biofilm structures to antifungal agents.</abstract><type>Journal Article</type><journal>Frontiers in Cellular and Infection Microbiology</journal><volume>13</volume><journalNumber/><paginationStart/><paginationEnd/><publisher>Frontiers Media SA</publisher><placeOfPublication/><isbnPrint/><isbnElectronic/><issnPrint/><issnElectronic>2235-2988</issnElectronic><keywords>antifungal, alginate oligosaccharide, nystatin, Candida spp., biofilm</keywords><publishedDay>31</publishedDay><publishedMonth>1</publishedMonth><publishedYear>2023</publishedYear><publishedDate>2023-01-31</publishedDate><doi>10.3389/fcimb.2023.1122340</doi><url/><notes/><college>COLLEGE NANME</college><department>Biomedical Sciences</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>BMS</DepartmentCode><institution>Swansea University</institution><apcterm>Another institution paid the OA fee</apcterm><funders>This work was funded by the Research Council of Norway (228542/O30, 245598/O30, 281920), AlgiPharma AS, European Social Fund (KESS2 Programme 517052) and the Sêr Cymru II programme which is part-funded by Cardiff University and the European Regional Development Fund through the Welsh Government (80762-CU176).</funders><projectreference/><lastEdited>2024-02-01T15:56:42.4485472</lastEdited><Created>2023-02-03T08:52:19.5966293</Created><path><level id="1">Faculty of Medicine, Health and Life Sciences</level><level id="2">Swansea University Medical School - Biomedical Science</level></path><authors><author><firstname>Lydia</firstname><surname>Powell</surname><orcid>0000-0002-8641-0160</orcid><order>1</order></author><author><firstname>Jennifer Y. 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spelling	v2 62485 2023-02-03 Alginate oligosaccharides enhance the antifungal activity of nystatin against candidal biofilms 0e7e702952672bcbfdfd4974199202fb 0000-0002-8641-0160 Lydia Powell Lydia Powell true false 10f61f9c1248951c1a33f6a89498f37d 0000-0002-7803-7714 Lewis Francis Lewis Francis true false 2023-02-03 BMS Background: The increasing prevalence of invasive fungal infections in immuno-compromised patients is a considerable cause of morbidity and mortality. With the rapid emergence of antifungal resistance and an inadequate pipeline of new therapies, novel treatment strategies are now urgently required.Methods: The antifungal activity of the alginate oligosaccharide OligoG in conjunction with nystatin was tested against a range of Candida spp. (C. albicans, C. glabrata, C. parapsilosis, C. auris, C. tropicalis and C. dubliniensis), in both planktonic and biofilm assays, to determine its potential clinical utility to enhance the treatment of candidal infections. The effect of OligoG (0-6%) ± nystatin on Candida spp. was examined in minimum inhibitory concentration (MIC) and growth curve assays. Antifungal effects of OligoG and nystatin treatment on biofilm formation and disruption were characterized using confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM) and ATP cellular viability assays. Effects on the cell membrane were determined using permeability assays and transmission electron microscopy (TEM).Results: MIC and growth curve assays demonstrated the synergistic effects of OligoG (0-6%) with nystatin, resulting in an up to 32-fold reduction in MIC, and a significant reduction in the growth of C. parapsilosis and C. auris (minimum significant difference = 0.2 and 0.12 respectively). CLSM and SEM imaging demonstrated that the combination treatment of OligoG (4%) with nystatin (1 µg/ml) resulted in significant inhibition of candidal biofilm formation on glass and clinical grade silicone surfaces (p < 0.001), with increased cell death (p < 0.0001). The ATP biofilm disruption assay demonstrated a significant reduction in cell viability with OligoG (4%) alone and the combined OligoG/nystatin (MIC value) treatment (p < 0.04) for all Candida strains tested. TEM studies revealed the combined OligoG/nystatin treatment induced structural reorganization of the Candida cell membrane, with increased permeability when compared to the untreated control (p < 0.001).Conclusions: Antimicrobial synergy between OligoG and nystatin against Candida spp. highlights the potential utility of this combination therapy in the prevention and topical treatment of candidal biofilm infections, to overcome the inherent tolerance of biofilm structures to antifungal agents. Journal Article Frontiers in Cellular and Infection Microbiology 13 Frontiers Media SA 2235-2988 antifungal, alginate oligosaccharide, nystatin, Candida spp., biofilm 31 1 2023 2023-01-31 10.3389/fcimb.2023.1122340 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University Another institution paid the OA fee This work was funded by the Research Council of Norway (228542/O30, 245598/O30, 281920), AlgiPharma AS, European Social Fund (KESS2 Programme 517052) and the Sêr Cymru II programme which is part-funded by Cardiff University and the European Regional Development Fund through the Welsh Government (80762-CU176). 2024-02-01T15:56:42.4485472 2023-02-03T08:52:19.5966293 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science Lydia Powell 0000-0002-8641-0160 1 Jennifer Y. M. Adams 2 Sadik Quoraishi 3 Charlène Py 4 Anaϊs Oger 5 Salvatore A. Gazze 6 Lewis Francis 0000-0002-7803-7714 7 Christopher von Ruhland 8 David Owens 9 Philip D. Rye 10 Katja E. Hill 11 Manon F. Pritchard 12 David W. Thomas 13 62485__26726__b511abfe7bcc4d999e882afc385ed8f0.pdf 62485_VoR.pdf 2023-03-02T14:41:57.4168640 Output 6988205 application/pdf Version of Record true © 2023 Powell, Adams, Quoraishi, Py, Oger, Gazze, Francis, von Ruhland, Owens, Rye, Hill, Pritchard and Thomas. This is an openaccess article distributed under the terms of the Creative Commons Attribution License (CC BY). true eng http://creativecommons.org/licenses/by/4.0/
title	Alginate oligosaccharides enhance the antifungal activity of nystatin against candidal biofilms
spellingShingle	Alginate oligosaccharides enhance the antifungal activity of nystatin against candidal biofilms Lydia Powell Lewis Francis
title_short	Alginate oligosaccharides enhance the antifungal activity of nystatin against candidal biofilms
title_full	Alginate oligosaccharides enhance the antifungal activity of nystatin against candidal biofilms
title_fullStr	Alginate oligosaccharides enhance the antifungal activity of nystatin against candidal biofilms
title_full_unstemmed	Alginate oligosaccharides enhance the antifungal activity of nystatin against candidal biofilms
title_sort	Alginate oligosaccharides enhance the antifungal activity of nystatin against candidal biofilms
author_id_str_mv	0e7e702952672bcbfdfd4974199202fb 10f61f9c1248951c1a33f6a89498f37d
author_id_fullname_str_mv	0e7e702952672bcbfdfd4974199202fb_*_Lydia Powell 10f61f9c1248951c1a33f6a89498f37d_*_Lewis Francis
author	Lydia Powell Lewis Francis
author2	Lydia Powell Jennifer Y. M. Adams Sadik Quoraishi Charlène Py Anaϊs Oger Salvatore A. Gazze Lewis Francis Christopher von Ruhland David Owens Philip D. Rye Katja E. Hill Manon F. Pritchard David W. Thomas
format	Journal article
container_title	Frontiers in Cellular and Infection Microbiology
container_volume	13
publishDate	2023
institution	Swansea University
issn	2235-2988
doi_str_mv	10.3389/fcimb.2023.1122340
publisher	Frontiers Media SA
college_str	Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id	facultyofmedicinehealthandlifesciences
hierarchy_top_title	Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id	facultyofmedicinehealthandlifesciences
hierarchy_parent_title	Faculty of Medicine, Health and Life Sciences
department_str	Swansea University Medical School - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science
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description	Background: The increasing prevalence of invasive fungal infections in immuno-compromised patients is a considerable cause of morbidity and mortality. With the rapid emergence of antifungal resistance and an inadequate pipeline of new therapies, novel treatment strategies are now urgently required.Methods: The antifungal activity of the alginate oligosaccharide OligoG in conjunction with nystatin was tested against a range of Candida spp. (C. albicans, C. glabrata, C. parapsilosis, C. auris, C. tropicalis and C. dubliniensis), in both planktonic and biofilm assays, to determine its potential clinical utility to enhance the treatment of candidal infections. The effect of OligoG (0-6%) ± nystatin on Candida spp. was examined in minimum inhibitory concentration (MIC) and growth curve assays. Antifungal effects of OligoG and nystatin treatment on biofilm formation and disruption were characterized using confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM) and ATP cellular viability assays. Effects on the cell membrane were determined using permeability assays and transmission electron microscopy (TEM).Results: MIC and growth curve assays demonstrated the synergistic effects of OligoG (0-6%) with nystatin, resulting in an up to 32-fold reduction in MIC, and a significant reduction in the growth of C. parapsilosis and C. auris (minimum significant difference = 0.2 and 0.12 respectively). CLSM and SEM imaging demonstrated that the combination treatment of OligoG (4%) with nystatin (1 µg/ml) resulted in significant inhibition of candidal biofilm formation on glass and clinical grade silicone surfaces (p < 0.001), with increased cell death (p < 0.0001). The ATP biofilm disruption assay demonstrated a significant reduction in cell viability with OligoG (4%) alone and the combined OligoG/nystatin (MIC value) treatment (p < 0.04) for all Candida strains tested. TEM studies revealed the combined OligoG/nystatin treatment induced structural reorganization of the Candida cell membrane, with increased permeability when compared to the untreated control (p < 0.001).Conclusions: Antimicrobial synergy between OligoG and nystatin against Candida spp. highlights the potential utility of this combination therapy in the prevention and topical treatment of candidal biofilm infections, to overcome the inherent tolerance of biofilm structures to antifungal agents.
published_date	2023-01-31T15:56:43Z
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Alginate oligosaccharides enhance the antifungal activity of nystatin against candidal biofilms

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