Alginate oligosaccharides enhance the antifungal activity of nystatin against candidal biofilms
BackgroundThe 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.Me...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-01-01
|
| Series: | Frontiers in Cellular and Infection Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2023.1122340/full |
| _version_ | 1797938722342174720 |
|---|---|
| author | Lydia C. Powell Lydia C. Powell Jennifer Y. M. Adams Sadik Quoraishi Charlène Py Charlène Py Anaϊs Oger Anaϊs Oger Salvatore A. Gazze Lewis W. Francis Christopher von Ruhland David Owens Philip D. Rye Katja E. Hill Manon F. Pritchard David W. Thomas |
| author_facet | Lydia C. Powell Lydia C. Powell Jennifer Y. M. Adams Sadik Quoraishi Charlène Py Charlène Py Anaϊs Oger Anaϊs Oger Salvatore A. Gazze Lewis W. Francis Christopher von Ruhland David Owens Philip D. Rye Katja E. Hill Manon F. Pritchard David W. Thomas |
| author_sort | Lydia C. Powell |
| collection | DOAJ |
| description | BackgroundThe 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.MethodsThe 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).ResultsMIC 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).ConclusionsAntimicrobial 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. |
| first_indexed | 2024-04-10T19:04:07Z |
| format | Article |
| id | doaj.art-15a722be6ea743308e6d0029bab58774 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-04-10T19:04:07Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-15a722be6ea743308e6d0029bab587742023-01-31T04:58:29ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882023-01-011310.3389/fcimb.2023.11223401122340Alginate oligosaccharides enhance the antifungal activity of nystatin against candidal biofilmsLydia C. Powell0Lydia C. Powell1Jennifer Y. M. Adams2Sadik Quoraishi3Charlène Py4Charlène Py5Anaϊs Oger6Anaϊs Oger7Salvatore A. Gazze8Lewis W. Francis9Christopher von Ruhland10David Owens11Philip D. Rye12Katja E. Hill13Manon F. Pritchard14David W. Thomas15Advanced Therapies Group, Cardiff University School of Dentistry, Cardiff, United KingdomMicrobiology and Infectious Disease group, Swansea University Medical School, Swansea, United KingdomAdvanced Therapies Group, Cardiff University School of Dentistry, Cardiff, United KingdomOtolaryngology Department, New Cross Hospital, Wolverhampton, United KingdomAdvanced Therapies Group, Cardiff University School of Dentistry, Cardiff, United KingdomSchool of Engineering, University of Angers, Angers, FranceAdvanced Therapies Group, Cardiff University School of Dentistry, Cardiff, United KingdomSchool of Engineering, University of Angers, Angers, FranceCentre for Nanohealth, Swansea University Medical School, Swansea, United KingdomCentre for Nanohealth, Swansea University Medical School, Swansea, United KingdomCentral Biotechnology Services, Cardiff University School of Medicine, Cardiff, United KingdomHead and Neck Directorate, University Hospital of Wales, Cardiff, United KingdomAlgiPharma AS, Sandvika, NorwayAdvanced Therapies Group, Cardiff University School of Dentistry, Cardiff, United KingdomAdvanced Therapies Group, Cardiff University School of Dentistry, Cardiff, United KingdomAdvanced Therapies Group, Cardiff University School of Dentistry, Cardiff, United KingdomBackgroundThe 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.MethodsThe 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).ResultsMIC 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).ConclusionsAntimicrobial 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.https://www.frontiersin.org/articles/10.3389/fcimb.2023.1122340/fullantifungalalginate oligosaccharidenystatinCandida spp.biofilm |
| spellingShingle | Lydia C. Powell Lydia C. Powell Jennifer Y. M. Adams Sadik Quoraishi Charlène Py Charlène Py Anaϊs Oger Anaϊs Oger Salvatore A. Gazze Lewis W. Francis Christopher von Ruhland David Owens Philip D. Rye Katja E. Hill Manon F. Pritchard David W. Thomas Alginate oligosaccharides enhance the antifungal activity of nystatin against candidal biofilms Frontiers in Cellular and Infection Microbiology antifungal alginate oligosaccharide nystatin Candida spp. biofilm |
| title | 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_short | Alginate oligosaccharides enhance the antifungal activity of nystatin against candidal biofilms |
| title_sort | alginate oligosaccharides enhance the antifungal activity of nystatin against candidal biofilms |
| topic | antifungal alginate oligosaccharide nystatin Candida spp. biofilm |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2023.1122340/full |
| work_keys_str_mv | AT lydiacpowell alginateoligosaccharidesenhancetheantifungalactivityofnystatinagainstcandidalbiofilms AT lydiacpowell alginateoligosaccharidesenhancetheantifungalactivityofnystatinagainstcandidalbiofilms AT jenniferymadams alginateoligosaccharidesenhancetheantifungalactivityofnystatinagainstcandidalbiofilms AT sadikquoraishi alginateoligosaccharidesenhancetheantifungalactivityofnystatinagainstcandidalbiofilms AT charlenepy alginateoligosaccharidesenhancetheantifungalactivityofnystatinagainstcandidalbiofilms AT charlenepy alginateoligosaccharidesenhancetheantifungalactivityofnystatinagainstcandidalbiofilms AT anaïsoger alginateoligosaccharidesenhancetheantifungalactivityofnystatinagainstcandidalbiofilms AT anaïsoger alginateoligosaccharidesenhancetheantifungalactivityofnystatinagainstcandidalbiofilms AT salvatoreagazze alginateoligosaccharidesenhancetheantifungalactivityofnystatinagainstcandidalbiofilms AT lewiswfrancis alginateoligosaccharidesenhancetheantifungalactivityofnystatinagainstcandidalbiofilms AT christophervonruhland alginateoligosaccharidesenhancetheantifungalactivityofnystatinagainstcandidalbiofilms AT davidowens alginateoligosaccharidesenhancetheantifungalactivityofnystatinagainstcandidalbiofilms AT philipdrye alginateoligosaccharidesenhancetheantifungalactivityofnystatinagainstcandidalbiofilms AT katjaehill alginateoligosaccharidesenhancetheantifungalactivityofnystatinagainstcandidalbiofilms AT manonfpritchard alginateoligosaccharidesenhancetheantifungalactivityofnystatinagainstcandidalbiofilms AT davidwthomas alginateoligosaccharidesenhancetheantifungalactivityofnystatinagainstcandidalbiofilms |