Initial Results of the International Efforts in Screening New Agents against Candida auris
Abstract
:1. Introduction
2. Materials and Methods
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Spivak, E.S.; Hanson, K.E. Candida auris: An Emerging Fungal Pathogen. J. Clin. Microbiol. 2018, 56, e01588-17. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Du, H.; Bing, J.; Hu, T.; Ennis, C.L.; Nobile, C.J.; Huang, G. Candida auris: Epidemiology, biology, antifungal resistance, and virulence. PLoS Pathog. 2020, 16, e1008921. [Google Scholar] [CrossRef] [PubMed]
- Benelli, J.L.; Poester, V.R.; Munhoz, L.S.; Melo, A.M.; Trápaga, M.R.; Stevens, A.D.; Xavier, M.O. Ebselen and diphenyl diselenide against fungal pathogens: A systematic review. Med. Mycol. 2021, 59, 409–421. [Google Scholar] [CrossRef]
- Wall, G.; Chaturvedi, A.K.; Wormley, F.L.; Wiederhold, N.P.; Patterson, H.P.; Patterson, T.F.; Lopez-Ribot, J.L. Screening a Repurposing Library for Inhibitors of Multidrug-Resistant Candida auris Identifies Ebselen as a Repositionable Candidate for Antifungal Drug Development. Antimicrob. Agents Chemother. 2018, 62, e01084-18. [Google Scholar] [CrossRef] [Green Version]
- de Oliveira, H.C.; Monteiro, M.C.; Rossi, S.A.; Pemán, J.; Ruiz-Gaitán, A.; Mendes-Giannini, M.J.S.; Mellado, E.; Zaragoza, O. Identification of Off-Patent Compounds That Present Antifungal Activity Against the Emerging Fungal Pathogen Candida auris. Front. Cell. Infect. Microbiol. 2019, 9, 83. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vazquez-Munoz, R.; Lopez, F.D.; Lopez-Ribot, J.L. Silver Nanoantibiotics Display Strong Antifungal Activity against the Emergent Multidrug-Resistant Yeast Candida auris Under Both Planktonic and Biofilm Growing Conditions. Front. Microbiol. 2020, 11, 1673. [Google Scholar] [CrossRef] [PubMed]
- Billamboz, M.; Fatima, Z.; Hameed, S.; Jawhara, S. Promising Drug Candidates and New Strategies for Fighting against the Emerging Superbug Candida auris. Microorganisms 2021, 9, 634. [Google Scholar] [CrossRef] [PubMed]
- Cheng, Y.-S.; Roma, J.S.; Shen, M.; Fernandes, C.M.; Tsang, P.S.; Forbes, H.E.; Boshoff, H.; Lazzarini, C.; Del Poeta, M.; Zheng, W.; et al. Identification of Antifungal Compounds against Multidrug-Resistant Candida auris Utilizing a High-Throughput Drug-Repurposing Screen. Antimicrob. Agents Chemother. 2021, 65, e01305-20. [Google Scholar] [CrossRef]
- Bandara, N.; Samaranayake, L. Emerging and future strategies in the management of recalcitrant Candida auris. Med. Mycol. 2022, 60, myac008. [Google Scholar] [CrossRef] [PubMed]
- de Bem, A.F.; Portella, R.D.L.; Farina, M.; Perottoni, J.; Paixão, M.W.; Nogueira, C.W.; Rocha, J.B.T. Low Toxicity of Diphenyl Diselenide in Rabbits: A Long-Term Study. Basic Clin. Pharmacol. Toxicol. 2007, 101, 47–55. [Google Scholar] [CrossRef] [PubMed]
- de Bem, A.F.; Portella, R.D.L.; Perottoni, J.; Becker, E.; Bohrer, D.; Paixao, M.; Nogueira, C.W.; Zeni, G.; Rocha, J.B.T. Changes in biochemical parameters in rabbits blood after oral exposure to diphenyl diselenide for long periods. Chem. Interact. 2006, 162, 1–10. [Google Scholar] [CrossRef] [PubMed]
- Rosa, R.M.; de Oliveira, R.B.; Saffi, J.; Braga, A.L.; Roesler, R.; Dal-Pizzol, F.; Moreira, J.C.F.; Brendel, M.; Henriques, J.A.P. Pro-oxidant action of diphenyl diselenide in the yeast Saccharomyces cerevisiae exposed to ROS-generating conditions. Life Sci. 2005, 77, 2398–2411. [Google Scholar] [CrossRef] [PubMed]
- Rosseti, I.B.; Rocha, J.B.T.; Costa, M.S. Diphenyl diselenide (PhSe)2 inhibits biofilm formation by Candida albicans, increasing both ROS production and membrane permeability. J. Trace Elem. Med. Biol. 2015, 29, 289–295. [Google Scholar] [CrossRef] [PubMed]
- Larwood, D.J. Nikkomycin Z—Ready to Meet the Promise? J. Fungi 2020, 6, 261. [Google Scholar] [CrossRef] [PubMed]
- Becker, J.M.; Marcus, S.; Tullock, J.; Miller, D.; Krainer, E.; Khare, R.K.; Naider, F. Use of the Chitin-Synthesis Inhibitor Nikkomycin to Treat Disseminated Candidiasis in Mice. J. Infect. Dis. 1988, 157, 212–214. [Google Scholar] [CrossRef] [PubMed]
- Hector, R.F.; Zimmer, B.L.; Pappagianis, D. Evaluation of nikkomycins X and Z in murine models of coccidioidomycosis, histoplasmosis, and blastomycosis. Antimicrob. Agents Chemother. 1990, 34, 587–593. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Milewski, S.; Mignini, F.; Borowski, E. Synergistic action of nikkomycin X/Z with azole antifungals on Candida albicans. J. Gen. Microbiol. 1991, 137, 2155–2161. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, R.K.; Rinaldi, M.G. In Vitro Antifungal Activity of Nikkomycin Z in Combination with Fluconazole or Itraconazole. Antimicrob. Agents Chemother. 1999, 43, 1401–1405. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cheung, Y.-Y.; Hui, M. Effects of Echinocandins in Combination with Nikkomycin Z against Invasive Candida albicans Bloodstream Isolates and the fks Mutants. Antimicrob. Agents Chemother. 2017, 61, e00619-17. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kovács, R.; Nagy, F.; Tóth, Z.; Bozó, A.; Balázs, B.; Majoros, L. Synergistic effect of nikkomycin Z with caspofungin and micafungin against Candida albicans and Candida parapsilosis biofilms. Lett. Appl. Microbiol. 2019, 69, 271–278. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hector, R.F.; Schaller, K. Positive interaction of nikkomycins and azoles against Candida albicans in vitro and in vivo. Antimicrob. Agents Chemother. 1992, 36, 1284–1289. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bentz, M.L.; Nunnally, N.; Lockhart, S.R.; Sexton, D.J.; Berkow, E.L. Antifungal activity of nikkomycin Z against Candida auris. J. Antimicrob. Chemother. 2021, 76, 1495–1497. [Google Scholar] [CrossRef] [PubMed]
- Fiedler, H.P. An overview of nikkomycins: History, biochemistry, and applications. In Cutaneous Antifungal Agents; Fromtling, R.A., Rippon, J.W., Eds.; Marcel-Dekker, Inc.: New York, NY, USA, 1993; pp. 325–352. [Google Scholar]
- Mohsin, J.; Weerakoon, S.; Ahmed, S.; Puts, Y.; Al Balushi, Z.; Meis, J.F.; Al-Hatmi, A.M.S. A Cluster of Candida auris Blood Stream Infections in a Tertiary Care Hospital in Oman from 2016 to 2019. Antibiotics 2020, 9, 638. [Google Scholar] [CrossRef] [PubMed]
- Paulmier, C. Selenium reagents and intermediates in organic synthesis. In Selenoorganic Functional Groups, 1st ed.; Pergamon Press: Oxford, UK, 1986; pp. 25–57. [Google Scholar]
- CLSI. Reference method for broth dilution antifungal susceptibility testing of yeasts. In CLSI Guideline M27, 4th ed.; Alexander, B., Ed.; Clinical and Laboratory Standards Institute: Berwyn, PA, USA, 2017. [Google Scholar]
- Eliopoulos, G.M.; Moellering, R.C. Antimicrobial combinations. In Antibiotics in Laboratory Medicine, 3rd ed.; Lorian, V., Ed.; Williams & Wilkins Co.: Baltimore, MD, USA, 1991; pp. 432–492. [Google Scholar]
- Goldberg, J.; Connolly, P.; Schnizlein-Bick, C.; Durkin, M.; Kohler, S.; Smedema, M.; Brizendine, E.; Hector, R.; Wheat, J. Comparison of Nikkomycin Z with Amphotericin B and Itraconazole for Treatment of Histoplasmosis in a Murine Model. Antimicrob. Agents Chemother. 2000, 44, 1624–1629. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hector, R.F.; Davidson, A.P.; Johnson, S.M. Comparison of susceptibility of fungal isolates to lufenuron and nikkomycin Z alone or in combination with itraconazole. Am. J. Veter-Res. 2005, 66, 1090–1093. [Google Scholar] [CrossRef]
- Poester, V.R.; Mattei, A.S.; Mendes, J.F.; Klafke, G.B.; Ramis, I.B.; Sanchotene, K.O.; Xavier, M.O. Antifungal activity of diphenyl diselenide alone and in combination with itraconazole against Sporothrix brasiliensis. Med. Mycol. 2019, 57, 328–331. [Google Scholar] [CrossRef]
- Centers for Disease Control and Prevention. Antifungal Susceptibility Testing and Interpretation 2020. Available online: https://www.cdc.gov/fungal/candida-auris/c-auris-antifungal.html (accessed on 18 May 2022).
- Melo, A.M.; Poester, V.R.; Trapaga, M.; Nogueira, C.W.; Zeni, G.; Martinez, M.; Sass, G.; Stevens, A.D.; Xavier, M.O. Diphenyl diselenide and its interaction with antifungals against Aspergillus spp. Med. Mycol. 2020, 59, 528–536. [Google Scholar] [CrossRef]
- Poester, V.R.; Munhoz, L.S.; Larwood, D.; Martinez, M.; Stevens, D.A.; Xavier, M.O. Potential use of Nikkomycin Z as an anti- Sporothrix spp. drug. Med. Mycol. 2021, 59, 345–349. [Google Scholar] [CrossRef]
- Maesaki, S.; Kohno, S.; Kaku, M.; Koga, H.; Hara, K. Effects of antifungal agent combinations administered simultaneously and sequentially against Aspergillus fumigatus. Antimicrob. Agents Chemother. 1994, 38, 2843–2845. [Google Scholar] [CrossRef] [Green Version]
- Stevens, D.A.; Espiritu, M.; Parmar, R. Paradoxical Effect of Caspofungin: Reduced Activity against Candida albicans at High Drug Concentrations. Antimicrob. Agents Chemother. 2004, 48, 3407–3411. [Google Scholar] [CrossRef] [Green Version]
- Thangamani, S.; Eldesouky, H.E.; Mohammad, H.; Pascuzzi, P.E.; Avramova, L.; Hazbun, T.R.; Seleem, M.N. Ebselen exerts antifungal activity by regulating glutathione (GSH) and reactive oxygen species (ROS) production in fungal cells. Biochim. et Biophys. Acta (BBA) Gen. Subj. 2016, 1861, 3002–3010. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hariharan, S.; Dharmaraj, S. Selenium and selenoproteins: It’s role in regulation of inflammation. Inflammopharmacology 2020, 28, 667–695. [Google Scholar] [CrossRef] [PubMed]
- Orie, N.N.; Warren, A.R.; Basaric, J.; Lau-Cam, C.; Piętka-Ottlik, M.; Młochowski, J.; Billack, B. In vitro assessment of the growth and plasma membrane H+-ATPase inhibitory activity of ebselen and structurally related selenium- and sulfur-containing compounds in Candida albicans. J. Biochem. Mol. Toxicol. 2017, 31, e21892. [Google Scholar] [CrossRef] [PubMed]
- Piętka-Ottlik, M.; Wójtowicz-Młochowska, H.; Kołodziejczyk, K.; Piasecki, E.; Młochowski, J. New Organoselenium Compounds Active against Pathogenic Bacteria, Fungi and Viruses. Chem. Pharm. Bull. 2008, 56, 1423–1427. [Google Scholar] [CrossRef] [Green Version]
- Perfect, J.R. Interactions between chitin and beta-glucan synthesis inhibitors. An new approach to antifungal development for cutaneous infections. In Cutaneous Antifungal Agents; Fromtling, R.A., Rippon, J.W., Eds.; Marcel-Dekker, Inc.: New York, NY, USA, 1993; pp. 365–375. [Google Scholar]
- Stevens, D.A. Drug Interaction Studies of a Glucan Synthase Inhibitor (LY 303366) and a Chitin Synthase Inhibitor (Nikkomycin Z) for Inhibition and Killing of Fungal Pathogens. Antimicrob. Agents Chemother. 2000, 44, 2547–2548. [Google Scholar] [CrossRef] [Green Version]
- Kim, M.-K.; Park, H.-S.; Kim, C.-H.; Park, H.-M.; Choi, W. Inhibitory effect of nikkomycin Z on chitin synthases in Candida albicans. Yeast 2002, 19, 341–349. [Google Scholar] [CrossRef]
Isolate # | MIC * (PhSe)2 Alone | MIC MYC Alone | FICi/INT ** (PhSe)2 + MYC | MIC AmB Alone | FICi/INT (PhSe)2 + AmB | MIC FCZ Alone | FICi/INT (PhSe)2 + FCZ |
---|---|---|---|---|---|---|---|
20-182 | >32 | 1 | 2/IND | 1-2 | >2/ANT | >64 | 2/IND |
20-184 | >32 | 1-2 | 2/IND | 1-2 | >2/ANT | >64 | 2/IND |
20-185 | >32 | 2 | ≤1.5/AD | 1-2 | >2/ANT | >64 | 2/IND |
20-187 | >32 | 1 | ≤1.25/AD | 2-4 | >2/ANT | >64 | 2/IND |
20-189 | >32 | 1-2 | 2/IND | 2-4 | >2/ANT | >64 | 2/IND |
20-193 | >32 | 1-2 | 2/IND | 2-4 | >2/ANT | 4 | >2/ANT |
20-195 | >32 | 1-2 | 2/IND | 2-4 | >2/ANT | >64 | 2/IND |
20-197 | >32 | 2 | ≤1.5/AD | 1-2 | >2/ANT | >64 | 2/IND |
20-198 | >32 | 1-2 | 2/IND | 2 | >2/ANT | >64 | 2/IND |
20-200 | >32 | 1 | 2/IND | 2-4 | >2/ANT | >64 | 2/IND |
Isolate # | MIC * NikZ Alone | MIC MYC Alone | FICi/INT ** NikZ + MYC | MIC AmB Alone | FICi/INT NikZ + AmB | MIC FCZ Alone | FICi/INT NikZ + FCZ |
---|---|---|---|---|---|---|---|
20-182 | >128 | 1 | ≤1.5/AD | 1-2 | ≤0.51/WS | >64 | 2/IND |
20-184 | >64 | 1-2 | ND | 1-2 | ≤0.5/WS | >64 | ≤0.28/SS |
20-185 | >64 | 2 | ND | 1-2 | ≤0.5/WS | >64 | ≤0.28/SS |
20-187 | >64 | 1 | ≤1.5/AD | 2-4 | ≤0.53/WS | >64 | 2/IND |
20-189 | >128 | 1-2 | ≤1.25/AD | 2-4 | 2/IND | >64 | 2/IND |
20-193 | >64 | 1-2 | ≤1.25/AD | 2-4 | ≤0.5/WS | 4 | ≤1/WS |
20-195 | >64 | 1-2 | ≤1/WS | 2-4 | ≤0.5/WS | >64 | 2/IND |
20-197 | >64 | 2 | ND | 1-2 | ≤0.63/WS | >64 | 2/IND |
20-198 | >64 | 1-2 | ≤1.5/AD | 2 | ≤0.5/WS | >64 | 2/IND |
20-200 | >64 | 1 | ≤1.25/AD | 2-4 | ≤0.5/WS | >64 | 2/IND |
MIC CAS alone | FICi/INT ** NikZ + CAS | ||||||
20-182 | >128 | 0.39 | ≤0.5/WS | ||||
20-184 | >64 | 25 | ≤0.25/SS | ||||
20-185 | >64 | 25 | ≤0.05/SS | ||||
20-189 | >128 | 0.39 | ≤0.5/WS | ||||
20-197 | >64 | 6.25 | ≤0.38/SS | ||||
20-247 | >128 | 3.13 | ≤0.27/SS |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 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
Poester, V.R.; Munhoz, L.S.; Benelli, J.L.; Melo, A.M.; Al-Hatmi, A.M.S.; Larwood, D.J.; Martinez, M.; Stevens, D.A.; Xavier, M.O. Initial Results of the International Efforts in Screening New Agents against Candida auris. J. Fungi 2022, 8, 771. https://doi.org/10.3390/jof8080771
Poester VR, Munhoz LS, Benelli JL, Melo AM, Al-Hatmi AMS, Larwood DJ, Martinez M, Stevens DA, Xavier MO. Initial Results of the International Efforts in Screening New Agents against Candida auris. Journal of Fungi. 2022; 8(8):771. https://doi.org/10.3390/jof8080771
Chicago/Turabian StylePoester, Vanice Rodrigues, Lívia Silveira Munhoz, Jéssica Louise Benelli, Aryse Martins Melo, Abdullah M. S. Al-Hatmi, David J. Larwood, Marife Martinez, David A. Stevens, and Melissa Orzechowski Xavier. 2022. "Initial Results of the International Efforts in Screening New Agents against Candida auris" Journal of Fungi 8, no. 8: 771. https://doi.org/10.3390/jof8080771