Investigating Candida glabrata Urinary Tract Infections (UTIs) in Mice Using Bioluminescence Imaging
Abstract
1. Introduction
2. Materials and Methods
2.1. Strains, Plasmids, and Growth Media
2.2. Urinary Tract Infection in Mice
2.3. Enzyme-Linked Immunosorbent Assay (ELISA)
2.4. In Vitro Luminescence Measurement
2.5. In Vivo Bioluminescence and Antifungal Treatment
3. Results
3.1. Fate of C. glabrata during Urinary Tract Infections
3.2. Expression of a Codon Adapted Red-Shifted Luciferase from the ENO1-Promoter Results in High Bioluminescence In Vitro
3.3. Expression of a Codon Adapted Red-Shifted Luciferase from the TEF1-Promoter Results in the Highest Luminescence In Vivo
3.4. In Vivo Monitoring of Treatment of a C. glabrata Urinary Tract Infection with Fluconazole
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Lamoth, F.; Lockhart, S.R.; Berkow, E.L.; Calandra, T. Changes in the epidemiological landscape of invasive candidiasis. J. Antimicrob. Chemother. 2018, 73, i4–i13. [Google Scholar] [CrossRef]
- Bolotin-Fukuhara, M.; Fairhead, C. Candida glabrata: A deadly companion? Yeast 2014, 31, 279–288. [Google Scholar] [CrossRef] [PubMed]
- Maccallum, D.M. Hosting infection: Experimental models to assay Candida virulence. Int. J. Microbiol. 2012, 2012, 363764. [Google Scholar] [CrossRef]
- Pfaller, M.A.; Diekema, D.J.; Turnidge, J.D.; Castanheira, M.; Jones, R.N. Twenty years of the SENTRY antifungal surveillance program: Results for Candida species from 1997–2016. Open Forum Infect. Dis. 2019, 6, S79–S94. [Google Scholar] [CrossRef]
- Horn, D.L.; Neofytos, D.; Anaissie, E.J.; Fishman, J.A.; Steinbach, W.J.; Olyaei, A.J.; Marr, K.A.; Pfaller, M.A.; Chang, C.H.; Webster, K.M. Epidemiology and outcomes of candidemia in 2019 patients: Data from the prospective antifungal therapy alliance registry. Clin. Infect. Dis. 2009, 48, 1695–1703. [Google Scholar] [CrossRef] [PubMed]
- Gabaldon, T.; Martin, T.; Marcet-Houben, M.; Durrens, P.; Bolotin-Fukuhara, M.; Lespinet, O.; Arnaise, S.; Boisnard, S.; Aguileta, G.; Atanasova, R.; et al. Comparative genomics of emerging pathogens in the Candida glabrata clade. BMC Genom. 2013, 14, 623. [Google Scholar] [CrossRef] [PubMed]
- Kurtzman, C.P.; Robnett, C.J. Three new insect-associated species of the yeast genus Candida. Can. J. Microbiol. 1998, 44, 965–973. [Google Scholar] [CrossRef][Green Version]
- Roetzer, A.; Gabaldon, T.; Schuller, C. From Saccharomyces cerevisiae to Candida glabratain a few easy steps: Important adaptations for an opportunistic pathogen. FEMS Microbiol. Lett. 2011, 314, 1–9. [Google Scholar] [CrossRef] [PubMed]
- Kurtzman, C.P.; Robnett, C.J. Phylogenetic relationships among yeasts of the ‘Saccharomyces complex’ determined from multigene sequence analyses. FEMS Yeast Res. 2003, 3, 417–432. [Google Scholar] [CrossRef]
- Domergue, R.; Castano, I.; De Las Penas, A.; Zupancic, M.; Lockatell, V.; Hebel, J.R.; Johnson, D.; Cormack, B.P. Nicotinic acid limitation regulates silencing of Candida adhesins during UTI. Science 2005, 308, 866–870. [Google Scholar] [CrossRef]
- Brieland, J.; Essig, D.; Jackson, C.; Frank, D.; Loebenberg, D.; Menzel, F.; Arnold, B.; DiDomenico, B.; Hare, R. Comparison of pathogenesis and host immune responses to Candida glabrata and Candida albicans in systemically infected immunocompetent mice. Infect. Immun. 2001, 69, 5046–5055. [Google Scholar] [CrossRef]
- Arendrup, M.; Horn, T.; Frimodt-Moller, N. In vivo pathogenicity of eight medically relevant Candida species in an animal model. Infection 2002, 30, 286–291. [Google Scholar] [CrossRef]
- Ferrari, S.; Sanguinetti, M.; De Bernardis, F.; Torelli, R.; Posteraro, B.; Vandeputte, P.; Sanglard, D. Loss of mitochondrial functions associated with azole resistance in Candida glabrata results in enhanced virulence in mice. Antimicrob. Agents Chemother. 2011, 55, 1852–1860. [Google Scholar] [CrossRef] [PubMed]
- Ferrari, S.; Sanguinetti, M.; Torelli, R.; Posteraro, B.; Sanglard, D. Contribution of CgPDR1-regulated genes in enhanced virulence of azole-resistant Candida glabrata. PLoS ONE 2011, 6, e17589. [Google Scholar] [CrossRef] [PubMed]
- Nakayama, H.; Ueno, K.; Uno, J.; Nagi, M.; Tanabe, K.; Aoyama, T.; Chibana, H.; Bard, M. Growth defects resulting from inhibiting ERG20 and RAM2 in Candida glabrata. FEMS Microbiol. Lett. 2011, 317, 27–33. [Google Scholar] [CrossRef]
- Van Dyck, K.; Rogiers, O.; Vande Velde, G.; Van Dijck, P. Let’s shine a light on fungal infections: A noninvasive imaging toolbox. PLoS Pathog. 2020, 16, e1008257. [Google Scholar] [CrossRef]
- Dorsaz, S.; Coste, A.T.; Sanglard, D. Red-shifted firefly luciferase optimized for Candida albiicans in vivo bioluminescence imaging. Front. Microbiol. 2017, 8, 1478. [Google Scholar] [CrossRef] [PubMed]
- Vande Velde, G.; Kucharikova, S.; Van Dijck, P.; Himmelreich, U. Bioluminescence imaging of fungal biofilm development in live animals. Methods Mol. Biol. 2014, 1098, 153–167. [Google Scholar] [CrossRef]
- Mosci, P.; Pericolini, E.; Gabrielli, E.; Kenno, S.; Perito, S.; Bistoni, F.; d’Enfert, C.; Vecchiarelli, A. A novel bioluminescence mouse model for monitoring oropharyngeal candidiasis in mice. Virulence 2013, 4, 250–254. [Google Scholar] [CrossRef]
- Enjalbert, B.; Rachini, A.; Vediyappan, G.; Pietrella, D.; Spaccapelo, R.; Vecchiarelli, A.; Brown, A.J.; d’Enfert, C. A multifunctional, synthetic Gaussia princeps luciferase reporter for live imaging of Candida albicans infections. Infect. Immun. 2009, 77, 4847–4858. [Google Scholar] [CrossRef]
- Pietrella, D.; Enjalbert, B.; Zeidler, U.; Znaidi, S.; Rachini, A.; Vecchiarelli, A.; d’Enfert, C. A luciferase reporter for gene expression studies and dynamic imaging of superficial Candida albicans infections. Methods Mol. Biol. 2012, 845, 537–546. [Google Scholar] [CrossRef]
- Ntziachristos, V.; Bremer, C.; Weissleder, R. Fluorescence imaging with near-infrared light: New technological advances that enable in vivo molecular imaging. Eur. Radiol. 2003, 13, 195–208. [Google Scholar] [CrossRef] [PubMed]
- Vande Velde, G.; Kucharikova, S.; Van Dijck, P.; Himmelreich, U. Bioluminescence imaging increases in vivo screening efficiency for antifungal activity against device-associated Candida albicans biofilms. Int. J. Antimicrob. Agents 2018, 52, 42–51. [Google Scholar] [CrossRef] [PubMed]
- Persyn, A.; Rogiers, O.; Brock, M.; Vande Velde, G.; Lamkanfi, M.; Jacobsen, I.D.; Himmelreich, U.; Lagrou, K.; Van Dijck, P.; Kucharikova, S. Monitoring of fluconazole and caspofungin activity against in vivo Candida glabrata biofilms by bioluminescence imaging. Antimicrob. Agents Chemother. 2019, 63, e01555-18. [Google Scholar] [CrossRef]
- Van Dyck, K.; Van Dijck, P.; Vande Velde, G. Bioluminescence imaging to study mature biofilm formation by Candida spp. and antifungal activity in vitro and in vivo. Methods Mol. Biol. 2020, 2081, 127–143. [Google Scholar] [CrossRef]
- Kaur, R.; Domergue, R.; Zupancic, M.L.; Cormack, B.P. A yeast by any other name: Candida glabrata and its interaction with the host. Curr. Opin. Microbiol. 2005, 8, 378–384. [Google Scholar] [CrossRef]
- Silva, S.; Negri, M.; Henriques, M.; Oliveira, R.; Williams, D.; Azeredo, J. Silicone colonization by non-Candida albicans Candida species in the presence of urine. J. Med. Microbiol. 2010, 59, 747–754. [Google Scholar] [CrossRef]
- Gharaghani, M.; Taghipour, S.; Halvaeezadeh, M.; Mahmoudabadi, A.Z. Candiduria: A review article with specific data from Iran. Turk. J. Urol. 2018, 44, 445–452. [Google Scholar] [CrossRef] [PubMed]
- Sierra-Diaz, E.; Hernandez-Rios, C.J.; Bravo-Cuellar, A. Antibiotic resistance: Microbiological profile of urinary tract infections in Mexico. Cir. Cir. 2019, 87, 176–182. [Google Scholar] [CrossRef]
- Peng, D.; Li, X.; Liu, P.; Luo, M.; Chen, S.; Su, K.; Zhang, Z.; He, Q.; Qiu, J.; Li, Y. Epidemiology of pathogens and antimicrobial resistanceof catheter-associated urinary tract infections in intensivecare units: A systematic review and meta-analysis. Am. J. Infect. Control 2018, 46, e81–e90. [Google Scholar] [CrossRef] [PubMed]
- Santana, M.M.P.; Hoffmann-Santos, H.D.; Dias, L.B.; Tadano, T.; Karhawi, A.S.K.; Dutra, V.; Candido, S.L.; Hahn, R.C. Epidemiological profile of patients hospitalized with candiduria in the central-western region of Brazil. Rev. Iberoam. Micol. 2019, 36, 175–180. [Google Scholar] [CrossRef] [PubMed]
- Jain, A.K.; Misra, V.; Ranjan, N.; Jain, S.B.; Gandhi, S. Speciation, biofilm formation and antifungal susceptibility of Candida isolates from clinically diagnosed patient of UTI in a tertiary care hospital. J. Assoc. Physicians India 2019, 67, 42–45. [Google Scholar] [PubMed]
- Gajdacs, M.; Doczi, I.; Abrok, M.; Lazar, A.; Burian, K. Epidemiology of candiduria and Candida urinary tract infections in inpatients and outpatients: Results from a 10-year retrospective survey. Cent. Eur. J. Urol. 2019, 72, 209–214. [Google Scholar] [CrossRef]
- Denis, B.; Chopin, D.; Piron, P.; Resche-Rigon, M.; Bretagne, S.; Gits-Muselli, M.; Peraldi, M.N.; Abboud, I.; Molina, J.M. Candiduria in kidney transplant recipients: Is antifungal therapy useful? Mycoses 2018, 61, 298–304. [Google Scholar] [CrossRef]
- Vale-Silva, L.; Ischer, F.; Leibundgut-Landmann, S.; Sanglard, D. Gain-of-function mutations in PDR1, a regulator of antifungal drug resistance in Candida glabrata, control adherence to host cells. Infect. Immun. 2013, 81, 1709–1720. [Google Scholar] [CrossRef]
- Zordan, R.E.; Ren, Y.; Pan, S.-J.; Rotondo, G.; de Las Peñas, A.; Iluore, J.; Cormack, B.P. Expression plasmids for use in Candida glabrata. G3 Genes Genomes Genet. 2013, 3, 1675–1686. [Google Scholar] [CrossRef]
- Vale-Silva, L.; Beaudoing, E.; Tran, V.D.T.; Sanglard, D. Comparative genomics of two sequential Candida glabrata clinical isolates. G3 Genes Genomes Genet. 2017, 7, 2413–2426. [Google Scholar] [CrossRef] [PubMed]
- Vale-Silva, L.A.; Moeckli, B.; Torelli, R.; Posteraro, B.; Sanguinetti, M.; Sanglard, D. Upregulation of the adhesin gene EPA1 mediated by PDR1 in Candida glabrata leads to enhanced host colonization. mSphere 2016, 1, e00065-15. [Google Scholar] [CrossRef] [PubMed]
- Silva, S.; Henriques, M.; Hayes, A.; Oliveira, R.; Azeredo, J.; Williams, D.W. Candida glabrata and Candida albicans co-infection of an in vitro oral epithelium. J. Oral Pathol. Med. 2011, 40, 421–427. [Google Scholar] [CrossRef]
- Perez-Torrado, R.; Querol, A. Saccharomyces cerevisiae show low levels of traversal across human endothelial barrier in vitro. F1000Research 2017, 6, 944. [Google Scholar] [CrossRef]
- Galocha, M.; Pais, P.; Cavalheiro, M.; Pereira, D.; Viana, R.; Teixeira, M.C. Divergent approaches to virulence in C. albicans and C. glabrata: Two sides of the same coin. Int. J. Mol. Sci. 2019, 20, 2345. [Google Scholar] [CrossRef]
- Fukuda, Y.; Tsai, H.F.; Myers, T.G.; Bennett, J.E. Transcriptional profiling of Candida glabrata during phagocytosis by neutrophils and in the infected mouse spleen. Infect. Immun. 2013, 81, 1325–1333. [Google Scholar] [CrossRef]
- Duggan, S.; Essig, F.; Hunniger, K.; Mokhtari, Z.; Bauer, L.; Lehnert, T.; Brandes, S.; Hader, A.; Jacobsen, I.D.; Martin, R.; et al. Neutrophil activation by Candida glabrata but not Candida albicans promotes fungal uptake by monocytes. Cell Microbiol. 2015, 17, 1259–1276. [Google Scholar] [CrossRef] [PubMed]
- Bourgeois, C.; Majer, O.; Frohner, I.E.; Lesiak-Markowicz, I.; Hildering, K.S.; Glaser, W.; Stockinger, S.; Decker, T.; Akira, S.; Muller, M.; et al. Conventional dendritic cells mount a type I IFN response against Candida spp. requiring novel phagosomal TLR7-mediated IFN-beta signaling. J. Immunol. 2011, 186, 3104–3112. [Google Scholar] [CrossRef] [PubMed]
- Riedelberger, M.; Penninger, P.; Tscherner, M.; Seifert, M.; Jenull, S.; Brunnhofer, C.; Scheidl, B.; Tsymala, I.; Bourgeois, C.; Petryshyn, A.; et al. Type I interferon response dysregulates host iron homeostasis and enhances Candida glabrata infection. Cell Host Microbe. 2020, 27, 454–466. [Google Scholar] [CrossRef] [PubMed]
- Seider, K.; Brunke, S.; Schild, L.; Jablonowski, N.; Wilson, D.; Majer, O.; Barz, D.; Haas, A.; Kuchler, K.; Schaller, M.; et al. The facultative intracellular pathogen Candida glabrata subverts macrophage cytokine production and phagolysosome maturation. J. Immunol. 2011, 187, 3072–3086. [Google Scholar] [CrossRef]
- Rai, M.N.; Balusu, S.; Gorityala, N.; Dandu, L.; Kaur, R. Functional genomic analysis of Candida glabrata-macrophage interaction: Role of chromatin remodeling in virulence. PLoS Pathog. 2012, 8, e1002863. [Google Scholar] [CrossRef]
- Kasper, L.; Seider, K.; Gerwien, F.; Allert, S.; Brunke, S.; Schwarzmuller, T.; Ames, L.; Zubiria-Barrera, C.; Mansour, M.K.; Becken, U.; et al. Identification of Candida glabrata genes involved in pH modulation and modification of the phagosomal environment in macrophages. PLoS ONE 2014, 9, e96015. [Google Scholar] [CrossRef] [PubMed]
- Rasheed, M.; Battu, A.; Kaur, R. Aspartyl proteases in Candida glabrata are required for suppression of the host innate immune response. J. Biol. Chem. 2018, 293, 6410–6433. [Google Scholar] [CrossRef]
- Jacobsen, I.D.; Brunke, S.; Seider, K.; Schwarzmuller, T.; Firon, A.; d’Enfert, C.; Kuchler, K.; Hube, B. Candida glabrata persistence in mice does not depend on host immunosuppression and is unaffected by fungal amino acid auxotrophy. Infect. Immun. 2010, 78, 1066–1077. [Google Scholar] [CrossRef]
- Chen, S.M.; Shen, H.; Zhang, T.; Huang, X.; Liu, X.Q.; Guo, S.Y.; Zhao, J.J.; Wang, C.F.; Yan, L.; Xu, G.T.; et al. Dectin-1 plays an important role in host defense against systemic Candida glabrata infection. Virulence 2017, 8, 1643–1656. [Google Scholar] [CrossRef]
- Nash, E.E.; Peters, B.M.; Lilly, E.A.; Noverr, M.C.; Fidel, P.L., Jr. A murine model of Candida glabrata vaginitis shows no evidence of an inflammatory immunopathogenic response. PLoS ONE 2016, 11, e0147969. [Google Scholar] [CrossRef]
- Willems, H.M.E.; Lowes, D.J.; Barker, K.S.; Palmer, G.E.; Peters, B.M. Comparative analysis of the capacity of the Candida species to elicit vaginal immunopathology. Infect. Immun. 2018, 86, e00527-18. [Google Scholar] [CrossRef]
- Wang, L.; Jackson, W.C.; Steinbach, P.A.; Tsien, R.Y. Evolution of new nonantibody proteins via iterative somatic hypermutation. Proc. Natl. Acad. Sci. USA 2004, 101, 16745–16749. [Google Scholar] [CrossRef]
- Gurskaya, N.G.; Fradkov, A.F.; Terskikh, A.; Matz, M.V.; Labas, Y.A.; Martynov, V.I.; Yanushevich, Y.G.; Lukyanov, K.A.; Lukyanov, S.A. GFP-like chromoproteins as a source of far-red fluorescent proteins. FEBS Lett. 2001, 507, 16–20. [Google Scholar] [CrossRef]
- Bergeron, A.C.; Seman, B.G.; Hammond, J.H.; Archambault, L.S.; Hogan, D.A.; Wheeler, R.T. Candida albicans and Pseudomonas aeruginosa interact to enhance virulence of mucosal infection in transparent zebrafish. Infect. Immun. 2017, 85, e00475-17. [Google Scholar] [CrossRef]
- Chapuis, A.F.; Ballou, E.R.; MacCallum, D.M. A bright future for fluorescence imaging of fungi in living hosts. J. Fungi 2019, 5, 29. [Google Scholar] [CrossRef] [PubMed]
- Rasheed, M.; Battu, A.; Kaur, R. Host-pathogen interaction in Candida glabrata infection: Current knowledge and implications for antifungal therapy. Expert Rev. Anti Infect. Ther. 2020, 18, 1093–1103. [Google Scholar] [CrossRef] [PubMed]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Schrevens, S.; Sanglard, D. Investigating Candida glabrata Urinary Tract Infections (UTIs) in Mice Using Bioluminescence Imaging. J. Fungi 2021, 7, 844. https://doi.org/10.3390/jof7100844
Schrevens S, Sanglard D. Investigating Candida glabrata Urinary Tract Infections (UTIs) in Mice Using Bioluminescence Imaging. Journal of Fungi. 2021; 7(10):844. https://doi.org/10.3390/jof7100844
Chicago/Turabian StyleSchrevens, Sanne, and Dominique Sanglard. 2021. "Investigating Candida glabrata Urinary Tract Infections (UTIs) in Mice Using Bioluminescence Imaging" Journal of Fungi 7, no. 10: 844. https://doi.org/10.3390/jof7100844
APA StyleSchrevens, S., & Sanglard, D. (2021). Investigating Candida glabrata Urinary Tract Infections (UTIs) in Mice Using Bioluminescence Imaging. Journal of Fungi, 7(10), 844. https://doi.org/10.3390/jof7100844