Lansoprazole interferes with fungal respiration and acts synergistically with amphotericin B against multidrug-resistant Candida auris

References

• Iyer KR, Camara K, Daniel-Ivad M, et al. An oxindole efflux inhibitor potentiates azoles and impairs virulence in the fungal pathogen Candida auris. Nat Commun. 2020 Dec 22;11(1):6429. doi:10.1038/s41467-020-20183-3
   PubMed Web of Science ®Google Scholar
• Eldesouky HE, Salama EA, Lanman NA, et al. Potent synergistic interactions between Lopinavir and Azole antifungal drugs against emerging multidrug-resistant Candida auris. Antimicrob Agents Ch. 2021 Jan;65(1). doi:10.1128/AAC.00684-20
   Web of Science ®Google Scholar
• Eldesouky HE, Li X, Abutaleb NS, et al. Synergistic interactions of sulfamethoxazole and azole antifungal drugs against emerging multidrug-resistant Candida auris. Int J Antimicrob Agents. 2018 Dec;52(6):754–761. doi:10.1016/j.ijantimicag.2018.08.016
   PubMed Web of Science ®Google Scholar
• Egger NB, Kainz K, Schulze A, et al. The rise of Candida auris: from unique traits to co-infection potential. Microb Cell. 2022 Aug 1;9(8):141–144. doi:10.15698/mic2022.08.782
   PubMed Web of Science ®Google Scholar
• Rossato L, Colombo AL. Candida auris: what have we learned about its mechanisms of pathogenicity? Front Microbiol. 2018;9:3081. doi:10.3389/fmicb.2018.03081
   PubMed Web of Science ®Google Scholar
• Vila T, Montelongo-Jauregui D, Ahmed H, et al. Comparative evaluations of the pathogenesis of Candida auris phenotypes and Candida albicans using clinically relevant murine models of infections. mSphere. 2020 Aug 5;5(4):1–13.
   Web of Science ®Google Scholar
• Eldesouky HE, Salama EA, Li X, et al. Repurposing approach identifies pitavastatin as a potent azole chemosensitizing agent effective against azole-resistant Candida species. Sci Rep. 2020 May 5;10(1):7525. doi:10.1038/s41598-020-64571-7
   PubMed Web of Science ®Google Scholar
• CDC. Antifungal susceptibility testing and interpretation in Candida auris, https://www.cdc.gov/fungal/candida-auris/c-auris-antifungal.html.
   Google Scholar
• Eldesouky HE, Lanman NA, Hazbun TR, et al. Aprepitant, an antiemetic agent, interferes with metal ion homeostasis of Candida auris and displays potent synergistic interactions with azole drugs. Virulence. 2020 Dec;11(1):1466–1481. doi:10.1080/21505594.2020.1838741
   PubMed Web of Science ®Google Scholar
• Lockhart SR, Etienne KA, Vallabhaneni S, et al. Simultaneous emergence of multidrug-resistant Candida auris on 3 continents confirmed by whole-genome sequencing and epidemiological analyses. Clin Infect Dis. 2017 Jan 15;64(2):134–140. doi:10.1093/cid/ciw691
   PubMed Web of Science ®Google Scholar
• Chowdhary A, Prakash A, Sharma C, et al. A multicentre study of antifungal susceptibility patterns among 350 Candida auris isolates (2009–17) in India: role of the ERG11 and FKS1 genes in azole and echinocandin resistance. J Antimicrob Chemoth. 2018 Apr;73(4):891–899. doi:10.1093/jac/dkx480
   PubMed Web of Science ®Google Scholar
• O'Brien B, Liang J, Chaturvedi S, et al. Pan-resistant Candida auris: New York subcluster susceptible to antifungal combinations. Lancet Microbe. 2020 Sep;1(5):e193–e194. doi:10.1016/S2666-5247(20)30090-2
   PubMedGoogle Scholar
• Lyman M, Forsberg K, Reuben J, et al. Notes from the field: transmission of Pan-resistant and Echinocandin-resistant Candida auris in health care facilities - Texas and the district of Columbia, January-April 2021. MMWR Morb Mortal Wkly Rep. 2021 Jul 23;70(29):1022–1023. doi:10.15585/mmwr.mm7029a2
   PubMed Web of Science ®Google Scholar
• Kohlenberg A, Monnet DL, Plachouras D, et al. Increasing number of cases and outbreaks caused by Candida auris in the EU/EEA, 2020 to 2021. Euro Surveill. 2022 Nov;27(46). doi:10.2807/1560-7917.ES.2022.27.46.2200846
   PubMedGoogle Scholar
• Taori SK, Khonyongwa K, Hayden I, et al. Candida auris outbreak: mortality, interventions and cost of sustaining control. J Infect. 2019 Dec;79(6):601–611. doi:10.1016/j.jinf.2019.09.007
   PubMed Web of Science ®Google Scholar
• Ruiz-Gaitan A, Martinez H, Moret AM, et al. Detection and treatment of Candida auris in an outbreak situation: risk factors for developing colonization and candidemia by this new species in critically ill patients. Expert Rev Anti Infect Ther. 2019 Apr;17(4):295–305. doi:10.1080/14787210.2019.1592675
   PubMed Web of Science ®Google Scholar
• de Oliveira Santos GC, Vasconcelos CC, Lopes AJO, et al. Candida infections and therapeutic strategies: mechanisms of action for traditional and alternative agents. Front Microbiol. 2018;9:1351. doi:10.3389/fmicb.2018.01351
   PubMed Web of Science ®Google Scholar
• Hill JA, Cowen LE. Using combination therapy to thwart drug resistance. Future Microbiol. 2015;10(11):1719–1726. doi:10.2217/fmb.15.68
   PubMed Web of Science ®Google Scholar
• One Health: Fungal Pathogens of Humans, Animals, and Plants: Report on an American Academy of Microbiology Colloquium held in Washington, DC, on October 18, 2017. American Academy of Microbiology Colloquia Reports. Washington (DC)2019.
   Google Scholar
• Cavassin FB, Bau-Carneiro JL, Vilas-Boas RR, et al. Sixty years of amphotericin B: an overview of the main antifungal agent used to treat invasive fungal infections. Infect Dis Ther. 2021 Mar;10(1):115–147. doi:10.1007/s40121-020-00382-7
   PubMed Web of Science ®Google Scholar
• Chaabane F, Graf A, Jequier L, et al. Review on antifungal resistance mechanisms in the emerging pathogen Candida auris. Front Microbiol. 2019;10:2788. doi:10.3389/fmicb.2019.02788
   PubMed Web of Science ®Google Scholar
• Carolus H, Pierson S, Lagrou K, et al. Amphotericin B and other polyenes-discovery, clinical Use, mode of action and drug resistance. J Fungi (Basel). 2020 Nov 27;6(4):1–21.
   Google Scholar
• Shekhar-Guturja T, Gunaherath GM, Wijeratne EM, et al. Dual action antifungal small molecule modulates multidrug efflux and TOR signaling. Nat Chem Biol. 2016 Oct;12(10):867–875. doi:10.1038/nchembio.2165
   PubMed Web of Science ®Google Scholar
• Eldesouky HE, Mayhoub A, Hazbun TR, et al. Reversal of azole resistance in Candida albicans by Sulfa antibacterial drugs. Antimicrob Agents Chemother. 2018 Mar;62(3). doi:10.1128/AAC.00701-17
   PubMed Web of Science ®Google Scholar
• CLSI. Reference method for broth dilution antifungal susceptibility testing of yeasts. In: 4th ed. CLSI standard M27. Wayne, PA: Clinical and Laboratory Standards Institute; 2017.
   Google Scholar
• Gu W, Guo D, Zhang L, et al. The synergistic effect of azoles and fluoxetine against resistant Candida albicans strains is attributed to attenuating fungal virulence. Antimicrob Agents Chemother. 2016 Oct;60(10):6179–6188. doi:10.1128/AAC.03046-15
   PubMed Web of Science ®Google Scholar
• Eldesouky HE, Salama EA, Hazbun TR, et al. Ospemifene displays broad-spectrum synergistic interactions with itraconazole through potent interference with fungal efflux activities. Sci Rep. 2020 Apr 8;10(1):6089. doi:10.1038/s41598-020-62976-y
   PubMed Web of Science ®Google Scholar
• Thangamani S, Eldesouky HE, Mohammad H, et al. Ebselen exerts antifungal activity by regulating glutathione (GSH) and reactive oxygen species (ROS) production in fungal cells. Biochim Biophys Acta Gen Subj. 2017 Jan;1861(1 Pt A):3002–3010. doi:10.1016/j.bbagen.2016.09.029
   PubMed Web of Science ®Google Scholar
• Mohammad H, Elghazawy NH, Eldesouky HE, et al. Discovery of a novel dibromoquinoline compound exhibiting potent antifungal and antivirulence activity that targets metal Ion homeostasis. ACS Infect Dis. 2018 Mar 9;4(3):403–414. doi:10.1021/acsinfecdis.7b00215
   PubMed Web of Science ®Google Scholar
• Gaetani M, Sabatier P, Saei AA, et al. Proteome integral solubility alteration: A high-throughput proteomics assay for target deconvolution. J Proteome Res. 2019 Nov 1;18(11):4027–4037. doi:10.1021/acs.jproteome.9b00500
   PubMed Web of Science ®Google Scholar
• Peck Justice SA, Barron MP, Qi GD, et al. Mutant thermal proteome profiling for characterization of missense protein variants and their associated phenotypes within the proteome. J Biol Chem. 2020 Nov 27;295(48):16219–16238. doi:10.1074/jbc.RA120.014576
   PubMed Web of Science ®Google Scholar
• Chen S, Zhou Y, Chen Y, et al. Fastp: an ultra-fast all-in-one FASTQ preprocessor. Bioinformatics. 2018 Sep 1;34(17):i884–i890. doi:10.1093/bioinformatics/bty560
   PubMed Web of Science ®Google Scholar
• Dobin A, Davis CA, Schlesinger F, et al. STAR: ultrafast universal RNA-Seq aligner. Bioinformatics. 2013 Jan 1;29(1):15–21. doi:10.1093/bioinformatics/bts635
   PubMed Web of Science ®Google Scholar
• Liao Y, Smyth GK, Shi W. Featurecounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics. 2014 Apr 1;30(7):923–930. doi:10.1093/bioinformatics/btt656
   PubMed Web of Science ®Google Scholar
• Robinson MD, McCarthy DJ, Smyth GK. Edger: a bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 2010 Jan 1;26(1):139–140. doi:10.1093/bioinformatics/btp616
   PubMed Web of Science ®Google Scholar
• Wu T, Hu E, Xu S, et al. Clusterprofiler 4.0: a universal enrichment tool for interpreting omics data. Innovation (Camb). 2021 Aug 28;2(3):100141.
   PubMedGoogle Scholar
• Song Z, Clain J, Iorga BI, et al. Saccharomyces cerevisiae-based mutational analysis of the bc1 complex Qo site residue 279 to study the trade-off between atovaquone resistance and function. Antimicrob Agents Chemother. 2015 Jul;59(7):4053–4058. doi:10.1128/AAC.00710-15
   PubMed Web of Science ®Google Scholar
• Friesner RA, Murphy RB, Repasky MP, et al. Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes. J Med Chem. 2006 Oct 19;49(21):6177–6196. doi:10.1021/jm051256o
   PubMed Web of Science ®Google Scholar
• Elgammal Y, Salama EA, Seleem MN. Atazanavir Resensitizes Candida auris to Azoles. Antimicrob Agents Chemother. 2023 Apr 24;67:e0163122.
   PubMed Web of Science ®Google Scholar
• Salama EA, Eldesouky HE, Elgammal Y, et al. Lopinavir and ritonavir act synergistically with azoles against Candida auris in vitro and in a mouse model of disseminated candidiasis. Int J Antimicrob Agents. 2023 Sep;62(3):106906. doi:10.1016/j.ijantimicag.2023.106906
   PubMed Web of Science ®Google Scholar
• Elgammal Y, Salama EA, Seleem MN. Saquinavir potentiates itraconazole's antifungal activity against multidrug-resistant Candida auris in vitro andin vivo. Med Mycol. 2023 Sep 4;61(9). doi:10.1093/mmy/myad081
   PubMed Web of Science ®Google Scholar
• Cao J, Forrest JC, Zhang X. A screen of the NIH clinical collection small molecule library identifies potential anti-coronavirus drugs. Antiviral Res. 2015 Feb;114:1–10. doi:10.1016/j.antiviral.2014.11.010
   PubMed Web of Science ®Google Scholar
• Gaetani M, Zubarev RA. Proteome Integral Solubility Alteration (PISA) for high-throughput ligand target deconvolution with increased statistical significance and reduced sample amount. Methods Mol Biol. 2023;2554:91–106. doi:10.1007/978-1-0716-2624-5_7
   PubMedGoogle Scholar
• Rybniker J, Vocat A, Sala C, et al. Lansoprazole is an antituberculous prodrug targeting cytochrome bc1. Nat Commun. 2015 Jul 9;6:7659. doi:10.1038/ncomms8659
   PubMed Web of Science ®Google Scholar
• Okamoto Y, Aoki S, Mataga I. Enhancement of amphotericin B activity against Candida albicans by superoxide radical. Mycopathologia. 2004 Jul;158(1):9–15. doi:10.1023/B:MYCO.0000038430.20669.80
   PubMed Web of Science ®Google Scholar
• Lopez-Velazquez G, Fernandez-Lainez C, de la Mora-de la Mora JI, et al. On the molecular and cellular effects of omeprazole to further support its effectiveness as an antigiardial drug. Sci Rep. 2019 Jun 20;9(1):8922. doi:10.1038/s41598-019-45529-w
   PubMedGoogle Scholar
• Brandt P, Mirhakkak MH, Wagner L, et al. High-Throughput profiling of Candida auris isolates reveals clade-specific metabolic differences. Microbiol Spectr. 2023 Jun 15;11(3):e0049823. doi:10.1128/spectrum.00498-23
   PubMed Web of Science ®Google Scholar
• Dantas Ada S, Day A, Ikeh M, et al. Oxidative stress responses in the human fungal pathogen, Candida albicans. Biomolecules. 2015 Feb 25;5(1):142–165. doi:10.3390/biom5010142
   PubMed Web of Science ®Google Scholar
• Temple MD, Perrone GG, Dawes IW. Complex cellular responses to reactive oxygen species. Trends Cell Biol. 2005 Jun;15(6):319–326. doi:10.1016/j.tcb.2005.04.003
   PubMed Web of Science ®Google Scholar
• Satoh K, Makimura K, Hasumi Y, et al. Candida auris sp. nov., a novel ascomycetous yeast isolated from the external ear canal of an inpatient in a Japanese hospital. Microbiol Immunol. 2009 Jan;53(1):41–44. doi:10.1111/j.1348-0421.2008.00083.x
   PubMed Web of Science ®Google Scholar
• Hill P, Kessl J, Fisher N, et al. Recapitulation in Saccharomyces cerevisiae of cytochrome b mutations conferring resistance to atovaquone in pneumocystis jiroveci. Antimicrob Agents Chemother. 2003 Sep;47(9):2725–2731. doi:10.1128/AAC.47.9.2725-2731.2003
   PubMed Web of Science ®Google Scholar
• Birth D, Kao WC, Hunte C. Structural analysis of atovaquone-inhibited cytochrome bc1 complex reveals the molecular basis of antimalarial drug action. Nat Commun. 2014 Jun 4;5:4029. doi:10.1038/ncomms5029
   PubMed Web of Science ®Google Scholar
• Forsberg K, Woodworth K, Walters M, et al. Candida auris: the recent emergence of a multidrug-resistant fungal pathogen. Med Mycol. 2019 Jan 1;57(1):1–12. doi:10.1093/mmy/myy054
   PubMed Web of Science ®Google Scholar
• Montoya MC, Moye-Rowley WS, Krysan DJ. Candida auris: the Canary in the mine of antifungal drug resistance. ACS Infect Dis. 2019 Sep 13;5(9):1487–1492. doi:10.1021/acsinfecdis.9b00239
   PubMed Web of Science ®Google Scholar
• Jacobs SE, Jacobs JL, Dennis EK, et al. Candida auris Pan-drug-resistant to four classes of antifungal agents. Antimicrob Agents Chemother. 2022 Jul 19;66(7):e0005322. doi:10.1128/aac.00053-22
   PubMed Web of Science ®Google Scholar
• Mesa-Arango AC, Trevijano-Contador N, Roman E, et al. The production of reactive oxygen species is a universal action mechanism of Amphotericin B against pathogenic yeasts and contributes to the fungicidal effect of this drug. Antimicrob Agents Chemother. 2014 Nov;58(11):6627–6638. doi:10.1128/AAC.03570-14
   PubMed Web of Science ®Google Scholar
• Di Trani JM, Liu Z, Whitesell L, et al. Rieske head domain dynamics and indazole-derivative inhibition of Candida albicans complex III. Structure. 2022 Jan 6;30(1):129–138 e4. doi:10.1016/j.str.2021.08.006
   PubMed Web of Science ®Google Scholar
• Sokol-Anderson M, Sligh JE Jr., Elberg S, et al. Role of cell defense against oxidative damage in the resistance of Candida albicans to the killing effect of amphotericin B. Antimicrob Agents Chemother. 1988 May;32(5):702–705. doi:10.1128/AAC.32.5.702
   PubMed Web of Science ®Google Scholar
• Drose S, Brandt U. The mechanism of mitochondrial superoxide production by the cytochrome bc1 complex. J Biol Chem. 2008 Aug 1;283(31):21649–21654. doi:10.1074/jbc.M803236200
   PubMed Web of Science ®Google Scholar
• Zamith-Miranda D, Heyman HM, Cleare LG, et al. Multi-omics signature of Candida auris, an emerging and multidrug-resistant pathogen. mSystems. 2019 Jun 11;4(4):1–14.
   Web of Science ®Google Scholar
• Musso L, Fabbrini A, Dallavalle S. Natural compound-derived cytochrome bc1 complex inhibitors as antifungal agents. Molecules. 2020 Oct 7;25(19):1–28.
   Web of Science ®Google Scholar
• Vincent BM, Langlois JB, Srinivas R, et al. A fungal-selective cytochrome bc(1) inhibitor impairs virulence and prevents the evolution of drug resistance. Cell Chem Biol. 2016 Aug 18;23(8):978–991. doi:10.1016/j.chembiol.2016.06.016
   PubMed Web of Science ®Google Scholar
• Guidarelli A, Brambilla L, Rota C, et al. The respiratory-chain poison antimycin A promotes the formation of DNA single-strand breaks and reduces toxicity in U937 cells exposed to t-butylhydroperoxide. Biochem J. 1996 Jul 15;317(Pt 2):371–375. doi:10.1042/bj3170371
   PubMedGoogle Scholar
• Simm C, Luan CH, Weiss E, et al. High-throughput screen for identifying small molecules that target fungal zinc homeostasis. PLoS One. 2011;6(9):e25136. doi:10.1371/journal.pone.0025136
   PubMed Web of Science ®Google Scholar