Antiviral lectin Q-Griffithsin suppresses fungal infection in murine models of vaginal candidiasis
Resistance to antifungal agents in vulvovaginal candidiasis has resulted in increasing morbidity among women globally. It is therefore crucial that new antimycotic agents are developed to counter this rising challenge. Q-Griffithsin (Q-GRFT) is a red algal lectin, manufactured in Nicotiana benthamia...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-10-01
|
| Series: | Frontiers in Cellular and Infection Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2022.976033/full |
| _version_ | 1811251434816012288 |
|---|---|
| author | Henry W. Nabeta Henry W. Nabeta Amanda B. Lasnik Joshua L. Fuqua Joshua L. Fuqua Lin Wang Lisa C. Rohan Lisa C. Rohan Lisa C. Rohan Kenneth E. Palmer Kenneth E. Palmer Kenneth E. Palmer |
| author_facet | Henry W. Nabeta Henry W. Nabeta Amanda B. Lasnik Joshua L. Fuqua Joshua L. Fuqua Lin Wang Lisa C. Rohan Lisa C. Rohan Lisa C. Rohan Kenneth E. Palmer Kenneth E. Palmer Kenneth E. Palmer |
| author_sort | Henry W. Nabeta |
| collection | DOAJ |
| description | Resistance to antifungal agents in vulvovaginal candidiasis has resulted in increasing morbidity among women globally. It is therefore crucial that new antimycotic agents are developed to counter this rising challenge. Q-Griffithsin (Q-GRFT) is a red algal lectin, manufactured in Nicotiana benthamiana. Griffithsin has well characterized broad spectrum antiviral activity and has demonstrated potent in vitro activity against multiple strains of Candida, including C. albicans. We have been working to incorporate Q-GRFT into topical microbicide products to prevent HIV-1 and HSV-2 transmission. The goal of this study was to evaluate the efficacy of a prototype Q-GRFT dosage form in prophylactic and therapeutic murine models of vaginal candidiasis, through microbiologic, histopathologic, and immune studies. In a preventive model, in comparison with infected controls, Q-GRFT treatment resulted in a lower fungal burden but did not alter the number of vaginal neutrophils and monocytes. In a therapeutic model, Q-GRFT enhanced fungal clearance when compared with infected untreated controls. Finally, histopathology demonstrated lower vaginal colonization with C. albicans following Q-GRFT treatment. Our results demonstrate that Q-GRFT has significant preventive and therapeutic activity in vaginal candidiasis offering additional benefit as a topical microbicide for prevention of HIV-1 and HSV-2 transmission. |
| first_indexed | 2024-04-12T16:19:30Z |
| format | Article |
| id | doaj.art-de813598b2aa4ec8aaf50ac8712f0238 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-04-12T16:19:30Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-de813598b2aa4ec8aaf50ac8712f02382022-12-22T03:25:36ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882022-10-011210.3389/fcimb.2022.976033976033Antiviral lectin Q-Griffithsin suppresses fungal infection in murine models of vaginal candidiasisHenry W. Nabeta0Henry W. Nabeta1Amanda B. Lasnik2Joshua L. Fuqua3Joshua L. Fuqua4Lin Wang5Lisa C. Rohan6Lisa C. Rohan7Lisa C. Rohan8Kenneth E. Palmer9Kenneth E. Palmer10Kenneth E. Palmer11Department of Microbiology and Immunology, School of Medicine, University of Louisville, Louisville KY, United StatesCenter for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville, Louisville KY, United StatesCenter for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville, Louisville KY, United StatesCenter for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville, Louisville KY, United StatesDepartment of Pharmacology and Toxicology, School of Medicine, University of Louisville, Louisville KY, United StatesInfectious Diseases, Magee-Womens Research Institute, Pittsburgh, PA, United StatesInfectious Diseases, Magee-Womens Research Institute, Pittsburgh, PA, United StatesDepartment of Obstetrics, Gynecology, & Reproductive Sciences, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, PA, United StatesDepartment of Microbiology and Immunology, School of Medicine, University of Louisville, Louisville KY, United StatesCenter for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville, Louisville KY, United StatesDepartment of Pharmacology and Toxicology, School of Medicine, University of Louisville, Louisville KY, United StatesResistance to antifungal agents in vulvovaginal candidiasis has resulted in increasing morbidity among women globally. It is therefore crucial that new antimycotic agents are developed to counter this rising challenge. Q-Griffithsin (Q-GRFT) is a red algal lectin, manufactured in Nicotiana benthamiana. Griffithsin has well characterized broad spectrum antiviral activity and has demonstrated potent in vitro activity against multiple strains of Candida, including C. albicans. We have been working to incorporate Q-GRFT into topical microbicide products to prevent HIV-1 and HSV-2 transmission. The goal of this study was to evaluate the efficacy of a prototype Q-GRFT dosage form in prophylactic and therapeutic murine models of vaginal candidiasis, through microbiologic, histopathologic, and immune studies. In a preventive model, in comparison with infected controls, Q-GRFT treatment resulted in a lower fungal burden but did not alter the number of vaginal neutrophils and monocytes. In a therapeutic model, Q-GRFT enhanced fungal clearance when compared with infected untreated controls. Finally, histopathology demonstrated lower vaginal colonization with C. albicans following Q-GRFT treatment. Our results demonstrate that Q-GRFT has significant preventive and therapeutic activity in vaginal candidiasis offering additional benefit as a topical microbicide for prevention of HIV-1 and HSV-2 transmission.https://www.frontiersin.org/articles/10.3389/fcimb.2022.976033/fullGriffithsinQ-Griffithsinantifungalcandidiasisvaginallectins |
| spellingShingle | Henry W. Nabeta Henry W. Nabeta Amanda B. Lasnik Joshua L. Fuqua Joshua L. Fuqua Lin Wang Lisa C. Rohan Lisa C. Rohan Lisa C. Rohan Kenneth E. Palmer Kenneth E. Palmer Kenneth E. Palmer Antiviral lectin Q-Griffithsin suppresses fungal infection in murine models of vaginal candidiasis Frontiers in Cellular and Infection Microbiology Griffithsin Q-Griffithsin antifungal candidiasis vaginal lectins |
| title | Antiviral lectin Q-Griffithsin suppresses fungal infection in murine models of vaginal candidiasis |
| title_full | Antiviral lectin Q-Griffithsin suppresses fungal infection in murine models of vaginal candidiasis |
| title_fullStr | Antiviral lectin Q-Griffithsin suppresses fungal infection in murine models of vaginal candidiasis |
| title_full_unstemmed | Antiviral lectin Q-Griffithsin suppresses fungal infection in murine models of vaginal candidiasis |
| title_short | Antiviral lectin Q-Griffithsin suppresses fungal infection in murine models of vaginal candidiasis |
| title_sort | antiviral lectin q griffithsin suppresses fungal infection in murine models of vaginal candidiasis |
| topic | Griffithsin Q-Griffithsin antifungal candidiasis vaginal lectins |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2022.976033/full |
| work_keys_str_mv | AT henrywnabeta antivirallectinqgriffithsinsuppressesfungalinfectioninmurinemodelsofvaginalcandidiasis AT henrywnabeta antivirallectinqgriffithsinsuppressesfungalinfectioninmurinemodelsofvaginalcandidiasis AT amandablasnik antivirallectinqgriffithsinsuppressesfungalinfectioninmurinemodelsofvaginalcandidiasis AT joshualfuqua antivirallectinqgriffithsinsuppressesfungalinfectioninmurinemodelsofvaginalcandidiasis AT joshualfuqua antivirallectinqgriffithsinsuppressesfungalinfectioninmurinemodelsofvaginalcandidiasis AT linwang antivirallectinqgriffithsinsuppressesfungalinfectioninmurinemodelsofvaginalcandidiasis AT lisacrohan antivirallectinqgriffithsinsuppressesfungalinfectioninmurinemodelsofvaginalcandidiasis AT lisacrohan antivirallectinqgriffithsinsuppressesfungalinfectioninmurinemodelsofvaginalcandidiasis AT lisacrohan antivirallectinqgriffithsinsuppressesfungalinfectioninmurinemodelsofvaginalcandidiasis AT kennethepalmer antivirallectinqgriffithsinsuppressesfungalinfectioninmurinemodelsofvaginalcandidiasis AT kennethepalmer antivirallectinqgriffithsinsuppressesfungalinfectioninmurinemodelsofvaginalcandidiasis AT kennethepalmer antivirallectinqgriffithsinsuppressesfungalinfectioninmurinemodelsofvaginalcandidiasis |