Sodium houttuyfonate enhances the mono-therapy of fluconazole on oropharyngeal candidiasis (OPC) through HIF-1α/IL-17 axis by inhibiting cAMP mediated filamentation in Candida albicans-Candida glabrata dual biofilms

References

• Swidergall M, Filler SG, Hogan DA. Oropharyngeal candidiasis: fungal invasion and epithelial cell responses. PLoS Pathog. 2017;13:e1006056.
   PubMed Web of Science ®Google Scholar
• Gaffen SL, Moutsopoulos NM. Regulation of host-microbe interactions at oral mucosal barriers by type 17 immunity. Sci Immunol. 2020;5:eaau4594.
   PubMed Web of Science ®Google Scholar
• Hu L, He C, Zhao C, et al. Characterization of oral candidiasis and the Candida species profile in patients with oral mucosal diseases. Microb Pathog. 2019;134:103575.
   PubMed Web of Science ®Google Scholar
• Salehi M, Ahmadikia K, Mahmoudi S, et al. Oropharyngeal candidiasis in hospitalised COVID-19 patients from Iran: species identification and antifungal susceptibility pattern. Mycoses. 2020;63:771–778.
   PubMed Web of Science ®Google Scholar
• Rodrigues CF, Silva S, Henriques M. Candida glabrata: a review of its features and resistance. Eur J Clin Microbiol Infect Dis. 2014;33:673–688.
   PubMed Web of Science ®Google Scholar
• Goldman M, Cloud GA, Wade KD, et al. A randomized study of the use of fluconazole in continuous versus episodic therapy in patients with advanced HIV infection and a history of oropharyngeal candidiasis: AIDS clinical trials group study 323/mycoses study group study 40. Clin Infect Dis. 2005;41:1473–1480.
   PubMed Web of Science ®Google Scholar
• Rossoni RD, Barbosa JO, Vilela SF, et al. Competitive interactions between C. albicans, C. glabrata and C. krusei during biofilm formation and development of experimental candidiasis. PLoS One. 2015;10:e0131700.
   PubMed Web of Science ®Google Scholar
• Li Q, Liu J, Chen M, et al. Abundance interaction in Candida albicans and Candida glabrata mixed biofilms under diverse conditions. Med Mycol. 2020;59:158–167.
   Web of Science ®Google Scholar
• Silva S, Henriques M, Hayes A, et al. Candida glabrata and Candida albicans co-infection of an in vitro oral epithelium. J Oral Pathol Med. 2011;40:421–427.
   PubMed Web of Science ®Google Scholar
• Olson ML, Jayaraman A, Kao KC. Relative abundances of Candida albicans and Candida glabrata in in vitro coculture biofilms impact biofilm structure and formation. Appl Environ Microbiol. 2018;84:e02769–17.
   PubMed Web of Science ®Google Scholar
• Li Q, Liu J, Shao J, et al. Decreasing cell population of individual Candida species does not impair the virulence of Candida albicans and Candida glabrata mixed biofilms. Front Microbiol. 2019;10:1600.
   PubMed Web of Science ®Google Scholar
• Shao J, Lu K, Tian G, et al. Lab-scale preparations of Candida albicans and dual Candida albicans-Candida glabrata biofilms on the surface of medical-grade polyvinyl chloride (PVC) perfusion tube using a modified gravity-supported free-flow biofilm incubator (GS-FFBI). J Microbiol Methods. 2015;109:41–48.
   PubMed Web of Science ®Google Scholar
• Tati S, Davidow P, McCall A, et al. Candida glabrata binding to Candida albicans hyphae enables its development in oropharyngeal candidiasis. PLoS Pathog. 2016;12:e1005522.
   PubMed Web of Science ®Google Scholar
• Huang G, Huang Q, Wei Y, et al. Multiple roles and diverse regulation of the Ras/cAMP/protein kinase A pathway in Candida albicans. Mol Microbiol. 2019;111:6–16.
   PubMed Web of Science ®Google Scholar
• Hogan DA, Muhlschlegel FA. Candida albicans developmental regulation: adenylyl cyclase as a coincidence detector of parallel signals. Curr Opin Microbiol. 2011;14:682–686.
   PubMed Web of Science ®Google Scholar
• Hogan DA, Sundstrom P. The Ras/cAMP/PKA signaling pathway and virulence in Candida albicans. Future Microbiol. 2009;4:1263–1270.
   PubMed Web of Science ®Google Scholar
• Baillie GS, Douglas LJ. Role of dimorphism in the development of Candida albicans biofilms. J Med Microbiol. 1999;48:671–679.
   PubMed Web of Science ®Google Scholar
• Chandra J, Kuhn DM, Mukherjee PK, et al. Biofilm formation by the fungal pathogen Candida albicans: development, architecture, and drug resistance. J Bacteriol. 2001;183:5385–5394.
   PubMed Web of Science ®Google Scholar
• Kaur R, Domergue R, Zupancic ML, et al. A yeast by any other name: candida glabrata and its interaction with the host. Curr Opin Microbiol. 2005;8:378–384.
   PubMed Web of Science ®Google Scholar
• Kowalski CH, Morelli KA, Schultz D, et al. Fungal biofilm architecture produces hypoxic microenvironments that drive antifungal resistance. Proc Natl Acad Sci U S A. 2020;117:22473–22483.
   PubMed Web of Science ®Google Scholar
• Rossignol T, Ding C, Guida A, et al. Correlation between biofilm formation and the hypoxic response in Candida parapsilosis. Eukaryot Cell. 2009;8:550–559.
   PubMedGoogle Scholar
• Kowalski CH, Kerkaert JD, Liu KW, et al. Fungal biofilm morphology impacts hypoxia fitness and disease progression. Nat Microbiol. 2019;4:2430–2441.
   PubMed Web of Science ®Google Scholar
• Desai PR, van Wijlick L, Kurtz D, et al. Hypoxia and temperature regulated morphogenesis in Candida albicans. PLoS Genet. 2015;11:e1005447.
   PubMed Web of Science ®Google Scholar
• McGettrick AF, O’Neill LAJ. The role of HIF in immunity and inflammation. Cell Metab. 2020;32:524–536.
   PubMed Web of Science ®Google Scholar
• Conti HR, Shen F, Nayyar N, et al. Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis. J Exp Med. 2009;206:299–311.
   PubMed Web of Science ®Google Scholar
• Conti HR, Peterson AC, Brane L, et al. Oral-resident natural Th17 cells and γδ T cells control opportunistic Candida albicans infections. J Exp Med. 2014;211:2075–2084.
   PubMed Web of Science ®Google Scholar
• Verma AH, Richardson JP, Zhou C, et al. Oral epithelial cells orchestrate innate type 17 responses to Candida albicans through the virulence factor candidalysin. Sci Immunol. 2017;2:eaam8834.
   PubMed Web of Science ®Google Scholar
• Aggor FEY, Break TJ, Trevejo-Nuñez G, et al. Oral epithelial IL-22/STAT3 signaling licenses IL-17-mediated immunity to oral mucosal candidiasis. Sci Immunol. 2020;5:eaba0570.
   PubMed Web of Science ®Google Scholar
• Conti HR, Bruno VM, Childs EE, et al. IL-17 receptor signaling in oral epithelial cells is critical for protection against oropharyngeal candidiasis. Cell Host Microbe. 2016;20:606–617.
   PubMed Web of Science ®Google Scholar
• Dang EV, Barbi J, Yang HY, et al. Control of T(H)17/T(reg) balance by hypoxia-inducible factor 1. Cell. 2011;146:772–784.
   PubMed Web of Science ®Google Scholar
• Gaffen SL, Jain R, Garg AV, et al. The IL-23-IL-17 immune axis: from mechanisms to therapeutic testing. Nat Rev Immunol. 2014;14:585–600.
   PubMed Web of Science ®Google Scholar
• Nittayananta W. Oral fungi in HIV: challenges in antifungal therapies. Oral Dis. 2016;22(Suppl 1):107–113.
   PubMedGoogle Scholar
• Liu X, Zhong L, Xie J, et al. Sodium houttuyfonate: a review of its antimicrobial, anti-inflammatory and cardiovascular protective effects. Eur J Pharmacol. 2021;902:174110.
   PubMed Web of Science ®Google Scholar
• Shingnaisui K, Dey T, Manna P, et al. Therapeutic potentials of Houttuynia cordata Thunb. against inflammation and oxidative stress: a review. J Ethnopharmacol. 2018;220:35–43.
   PubMed Web of Science ®Google Scholar
• Sekita Y, Murakami K, Yumoto H, et al. Preventive effects of Houttuynia cordata extract for oral infectious diseases. Biomed Res Int. 2016;2016:2581876.
   PubMed Web of Science ®Google Scholar
• Sekita Y, Murakami K, Yumoto H, et al. Antibiofilm and anti-inflammatory activities of Houttuynia cordata decoction for oral care. Evid Based Complement Alternat Med. 2017;2017:2850947.
   PubMed Web of Science ®Google Scholar
• Shao J, Cheng H, Wu D, et al. Antimicrobial effect of sodium houttuyfonate on Staphylococcus epidermidis and Candida albicans biofilms. J Tradit Chin Med. 2013;33:798–803.
   PubMed Web of Science ®Google Scholar
• Shao J, Cui Y, Zhang M, et al. Synergistic in vitro activity of sodium houttuyfonate with fluconazole against clinical Candida albicans strains under planktonic growing conditions. Pharm Biol. 2017;55:355–359.
   PubMed Web of Science ®Google Scholar
• Huang W, Duan Q, Li F, et al. Sodium houttuyfonate and EDTA-Na₂ in combination effectively inhibits Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans in vitro and in vivo. Bioorg Med Chem Lett. 2015;25:142–147.
   PubMed Web of Science ®Google Scholar
• Ma K, Chen M, Liu J, et al. Sodium houttuyfonate attenuates dextran sulfate sodium associated colitis precolonized with Candida albicans through inducing β-glucan exposure. J Leukoc Biol. 2021;110:927–937.
   PubMed Web of Science ®Google Scholar
• Odds FC. Synergy, antagonism, and what the chequerboard puts between them. J Antimicrob Chemother. 2003;52:1.
   PubMed Web of Science ®Google Scholar
• Hosida TY, Cavazana TP, Henriques M, et al. Interactions between Candida albicans and Candida glabrata in biofilms: influence of the strain type, culture medium and glucose supplementation. Mycoses. 2018;61:270–278.
   PubMed Web of Science ®Google Scholar
• Yang LF, Liu X, Lv LL, et al. Dracorhodin perchlorate inhibits biofilm formation and virulence factors of Candida albicans. J Mycol Med. 2018;28:36–44.
   PubMed Web of Science ®Google Scholar
• Lindsay AK, Deveau A, Piispanen AE, et al. Farnesol and cyclic AMP signaling effects on the hypha-to-yeast transition in Candida albicans. Eukaryot Cell. 2012;11:1219–1225.
   PubMed Web of Science ®Google Scholar
• Nciki S, Oderinlo OO, Gulube Z, et al. Mezoneuron benthamianum inhibits cell adherence, hyphae formation, and phospholipase production in Candida albicans. Arch Microbiol. 2020;202:2533–2542.
   PubMed Web of Science ®Google Scholar
• Li Y, Shan M, Li S, et al. Teasaponin suppresses Candida albicans filamentation by reducing the level of intracellular cAMP. Ann Transl Med. 2020;8:175.
   PubMed Web of Science ®Google Scholar
• Solis NV, Filler SG. Mouse model of oropharyngeal candidiasis. Nat Protoc. 2012;7:637–642.
   PubMed Web of Science ®Google Scholar
• Takakura N, Wakabayashi H, Ishibashi H, et al. Oral lactoferrin treatment of experimental oral candidiasis in mice. Antimicrob Agents Chemother. 2003;47:2619–2623.
   PubMed Web of Science ®Google Scholar
• Khoury ZH, Vila T, Puthran TR, et al. The role of Candida albicans secreted polysaccharides in augmenting Streptococcus mutans adherence and mixed biofilm formation: in vitro and in vivo studies. Front Microbiol. 2020;11:307.
   PubMed Web of Science ®Google Scholar
• Tzoumas S, Nunes A, Olefir I, et al. Eigenspectra optoacoustic tomography achieves quantitative blood oxygenation imaging deep in tissues. Nat Commun. 2016;7:12121.
   PubMed Web of Science ®Google Scholar
• Palazon A, Tyrakis PA, Macias D, et al. An HIF-1α/VEGF-A axis in cytotoxic T cells regulates tumor progression. Cancer Cell. 2017;32(669–83.e5). doi:10.1016/j.ccell.2017.10.003.
   PubMedGoogle Scholar
• Hildebrand D, Kubatzky KF. Phospho-flow analysis of primary mouse cells after HDAC inhibitor treatment. Methods Mol Biol. 2017;1510:233–243.
   PubMedGoogle Scholar
• Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCt Method. Methods. 2001;25:402–408.
   PubMed Web of Science ®Google Scholar
• Rossoni RD, Barros PP, Freire F, et al. Study of microbial interaction formed by “Candida krusei” and “Candida glabrata”: “in vitro” and “in vivo” studies. Braz Dent J. 2017;28:669–674.
   PubMedGoogle Scholar
• Morici P, Fais R, Rizzato C, et al. Inhibition of Candida albicans biofilm formation by the synthetic lactoferricin derived peptide hLF1-11. PLoS One. 2016;11:e0167470.
   PubMed Web of Science ®Google Scholar
• Walters MC 3rd, Roe F, Bugnicourt A, et al. Contributions of antibiotic penetration, oxygen limitation, and low metabolic activity to tolerance of Pseudomonas aeruginosa biofilms to ciprofloxacin and tobramycin. Antimicrob Agents Chemother. 2003;47:317–323.
   PubMed Web of Science ®Google Scholar
• Lu L, Pan K, Zheng HX, et al. IL-17A promotes immune cell recruitment in human esophageal cancers and the infiltrating dendritic cells represent a positive prognostic marker for patient survival. J Immunother. 2013;36:451–458.
   PubMed Web of Science ®Google Scholar
• Consiglio CR, Udartseva O, Ramsey KD, et al. Enzalutamide, an androgen receptor antagonist, enhances myeloid cell-mediated immune suppression and tumor progression. Cancer Immunol Res. 2020;8:1215–1227.
   PubMed Web of Science ®Google Scholar
• Bennett JE, Izumikawa K, Marr KA. Mechanism of increased fluconazole resistance in Candida glabrata during prophylaxis. Antimicrob Agents Chemother. 2004;48:1773–1777.
   PubMed Web of Science ®Google Scholar
• Wagner H, Ulrich-Merzenich G. Synergy research: approaching a new generation of phytopharmaceuticals. Phytomedicine. 2009;16:97–110.
   PubMed Web of Science ®Google Scholar
• Sanguinetti M, Posteraro B, Lass-Flörl C. Antifungal drug resistance among Candida species: mechanisms and clinical impact. Mycoses. 2015;58(Suppl 2):2–13.
   PubMedGoogle Scholar
• Da W, Shao J, Li Q, et al. Physical interaction of sodium houttuyfonate with β-1,3-glucan evokes Candida albicans cell wall remodeling. Front Microbiol. 2019;10:34.
   PubMed Web of Science ®Google Scholar
• Csank C, Haynes K. Candida glabrata displays pseudohyphal growth. FEMS Microbiol Lett. 2000;189:115–120.
   PubMed Web of Science ®Google Scholar
• Hartmann H, Eltzschig HK, Wurz H, et al. Hypoxia-independent activation of HIF-1 by Enterobacteriaceae and their siderophores. Gastroenterology. 2008;134:756–767.
   PubMed Web of Science ®Google Scholar
• Yoo YG, Na TY, Seo HW, et al. Hepatitis B virus X protein induces the expression of MTA1 and HDAC1, which enhances hypoxia signaling in hepatocellular carcinoma cells. Oncogene. 2008;27:3405–3413.
   PubMed Web of Science ®Google Scholar
• Wiley M, KR S, DA C, et al. Toxoplasma gondii activates hypoxia-inducible factor (HIF) by stabilizing the HIF-1alpha subunit via type I activin-like receptor kinase receptor signaling. J Biol Chem. 2010;285:26852–26860.
   PubMed Web of Science ®Google Scholar
• Werth N, Beerlage C, Rosenberger C, et al. Activation of hypoxia inducible factor 1 is a general phenomenon in infections with human pathogens. PLoS One. 2010;5:e11576.
   PubMed Web of Science ®Google Scholar
• Hernández-Santos N, Gaffen SL. Th17 cells in immunity to Candida albicans. Cell Host Microbe. 2012;11:425–435.
   PubMed Web of Science ®Google Scholar
• Lopes JP, Stylianou M, Backman E, et al. Evasion of immune surveillance in low oxygen environments enhances Candida albicans virulence. mBio. 2018;9:e02120–18.
   PubMed Web of Science ®Google Scholar
• Pradhan A, Avelar GM, Bain JM, et al. Hypoxia promotes immune evasion by triggering β-glucan masking on the Candida albicans cell surface via mitochondrial and cAMP-protein kinase A signaling. mBio. 2018;9:e01318.
   PubMed Web of Science ®Google Scholar
• Wheeler RT, Fink GR. A drug-sensitive genetic network masks fungi from the immune system. PLoS Pathog. 2006;2:e35.
   PubMed Web of Science ®Google Scholar
• Guirao-Abad JP, Sánchez-Fresneda R, Machado F, et al. Micafungin enhances the human macrophage response to Candida albicans through β-glucan exposure. Antimicrob Agents Chemother. 2018;62:e02161–17.
   PubMed Web of Science ®Google Scholar
• Pradhan A, Avelar GM, Bain JM, et al. Non-canonical signalling mediates changes in fungal cell wall PAMPs that drive immune evasion. Nat Commun. 2019;10:5315.
   PubMed Web of Science ®Google Scholar
• Walker LA, Munro CA. Caspofungin induced cell wall changes of Candida species influences macrophage interactions. Front Cell Infect Microbiol. 2020;10:164.
   PubMed Web of Science ®Google Scholar
• Park H, Myers CL, Sheppard DC, et al. Role of the fungal Ras-protein kinase A pathway in governing epithelial cell interactions during oropharyngeal candidiasis. Cell Microbiol. 2005;7:499–510.
   PubMed Web of Science ®Google Scholar
• Gladiator A, Wangler N, Trautwein-Weidner K, et al. Cutting edge: IL-17-secreting innate lymphoid cells are essential for host defense against fungal infection. J Immunol. 2013;190:521–525.
   PubMed Web of Science ®Google Scholar
• Colgan SP, Furuta GT, Taylor CT. Hypoxia and innate immunity: keeping up with the HIFsters. Annu Rev Immunol. 2020;38:341–363.
   PubMed Web of Science ®Google Scholar
• Swidergall M, Solis NV, Millet N, et al. Activation of EphA2-EGFR signaling in oral epithelial cells by Candida albicans virulence factors. PLoS Pathog. 2021;17:e1009221.
   PubMed Web of Science ®Google Scholar
• Swidergall M, Solis NV, Wang Z, et al. EphA2 is a neutrophil receptor for Candida albicans that stimulates antifungal activity during oropharyngeal infection. Cell Rep. 2019;28:423–33.e5.
   PubMed Web of Science ®Google Scholar
• Swidergall M, Solis NV, Lionakis MS, et al. EphA2 is an epithelial cell pattern recognition receptor for fungal β-glucans. Nat Microbiol. 2018;3:53–61.
   PubMed Web of Science ®Google Scholar