Antifungal resistance: Emerging mechanisms and implications (Review)
- Authors:
- Ika N. Kadariswantiningsih
- Maulana A. Empitu
- Timotius Imanuel Santosa
- Yikelamu Alimu
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Affiliations: Department of Medical Microbiology, Faculty of Medicine, Airlangga University, Surabaya, East Java 60131, Indonesia, Department of Pharmacology, Faculty of Medicine, Airlangga University, Surabaya, East Java 60131, Indonesia, Department of Cutaneous Allergy and Host Defense, Immunology Frontier Research Center, Osaka University, Osaka, Honshu 5650871, Japan - Published online on: July 8, 2025 https://doi.org/10.3892/mmr.2025.13612
- Article Number: 247
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Copyright: © Kadariswantiningsih et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
This article is mentioned in:
Abstract
 |
|
Bongomin F, Gago S, Oladele RO and Denning DW: Global and multi-national prevalence of fungal diseases-estimate precision. J Fungi (Basel). 3:572017. View Article : Google Scholar : PubMed/NCBI | |
|
Brown GD, Denning DW, Gow NAR, Levitz SM, Netea MG and White TC: Hidden killers: Human fungal infections. Sci Transl Med. 4:165rv13. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Denning DW: Global incidence and mortality of severe fungal disease. Lancet Infect Dis. 24:e428–e438. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Fisher MC, Hawkins NJ, Sanglard D and Gurr SJ: Worldwide emergence of resistance to antifungal drugs challenges human health and food security. Science. 360:739–742. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Enoch DA, Yang H, Aliyu SH and Micallef C: The changing epidemiology of invasive fungal infections. Methods Mol Biol. 1508:17–65. 2017. View Article : Google Scholar | |
|
Lee Y, Puumala E, Robbins N and Cowen LE: Antifungal drug resistance: Molecular mechanisms in Candida albicans and beyond. Chem Rev. 121:3390–3411. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Maligie MA and Selitrennikoff CP: Cryptococcus neoformans resistance to echinocandins:(1, 3) β-glucan synthase activity is sensitive to echinocandins. Antimicrob Agents Chemother. 49:2851–2856. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Berkow EL and Lockhart SR: Fluconazole resistance in Candida species: A current perspective. Infect Drug Resist. 10:237–245. 2017. View Article : Google Scholar | |
|
Pfaller MA, Diekema DJ, Turnidge JD, Castanheira M and Jones RN: Twenty years of the SENTRY antifungal surveillance program: Results for Candida species from 1997–2016. Open Forum Infect Dis. 6 (Suppl 1):S79–S94. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Wuyts J, Van Dijck P and Holtappels M: Fungal persister cells: The basis for recalcitrant infections? PLoS Pathog. 14:e10073012018. View Article : Google Scholar : PubMed/NCBI | |
|
Berman J and Krysan DJ: Drug resistance and tolerance in fungi. Nat Rev Microbiol. 18:319–331. 2020. View Article : Google Scholar | |
|
Rosenberg AJ, Ene IV, Bibi M, Zakin S, Segal ES, Ziv N, Dahan AM, Colombo AL, Bennett RJ and Berman J: Antifungal tolerance is a subpopulation effect distinct from resistance and is associated with persistent candidemia. Nat Commun. 9:24702018. View Article : Google Scholar : PubMed/NCBI | |
|
Cowen LE, Sanglard D, Howard SJ, Rogers PD and Perlin DS: Mechanisms of antifungal drug resistance. Cold Spring Harb Perspect Med. 5:a0197522015. View Article : Google Scholar | |
|
Lee Y, Robbins N and Cowen LE: Molecular mechanisms governing antifungal drug resistance. NPJ Antimicrob Resist. 1:52023. View Article : Google Scholar | |
|
Revie NM, Iyer KR, Robbins N and Cowen LE: Antifungal drug resistance: Evolution, mechanisms and impact. Curr Opin Microbiol. 45:70–76. 2018. View Article : Google Scholar | |
|
Shapiro RS, Robbins N and Cowen LE: Regulatory circuitry governing fungal development, drug resistance, and disease. Microbiol Mol Biol Rev. 75:213–267. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Patra S, Raney M, Pareek A and Kaur R: Epigenetic regulation of antifungal drug resistance. J Fungi (Basel). 8:8752022. View Article : Google Scholar : PubMed/NCBI | |
|
Perea S and Patterson TF: Antifungal resistance in pathogenic fungi. Clin Infect Dis. 35:1073–1080. 2002. View Article : Google Scholar : PubMed/NCBI | |
|
Hosseini P, Keniya MV, Sagatova AA, Toepfer S, Müller C, Tyndall JDA, Klinger A, Fleischer E and Monk BC: The molecular basis of the intrinsic and acquired resistance to azole antifungals in Aspergillus fumigatus. J Fungi (Basel). 10:8202024. View Article : Google Scholar : PubMed/NCBI | |
|
Rosam K, Monk BC and Lackner M: Sterol 14α-Demethylase ligand-binding pocket-mediated acquired and intrinsic azole resistance in fungal pathogens. J Fungi (Basel). 7:10.3390/jof7010001. 2021. View Article : Google Scholar | |
|
Caramalho R, Tyndall JDA, Monk BC, Larentis T, Lass-Flörl C and Lackner M: Intrinsic short-tailed azole resistance in mucormycetes is due to an evolutionary conserved aminoacid substitution of the lanosterol 14α-demethylase. Sci Rep. 7:158982017. View Article : Google Scholar : PubMed/NCBI | |
|
Leonardelli F, Macedo D, Dudiuk C, Cabeza MS, Gamarra S and Garcia-Effron G: Aspergillus fumigatus intrinsic fluconazole resistance is due to the naturally occurring T301I substitution in Cyp51Ap. Antimicrob Agents Chemother. 60:5420–5426. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Cannon RD, Lamping E, Holmes AR, Niimi K, Baret PV, Keniya MV, Tanabe K, Niimi M, Goffeau A and Monk BC: Efflux-mediated antifungal drug resistance. Clin Microbiol Rev. 22:291–321. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Lamping E, Baret PV, Holmes AR, Monk BC, Goffeau A and Cannon RD: Fungal PDR transporters: Phylogeny, topology, motifs and function. Fungal Genet Biol. 47:127–142. 2010. View Article : Google Scholar | |
|
Kovalchuk A and Driessen AJM: Phylogenetic analysis of fungal ABC transporters. BMC Genomics. 11:1–21. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Chow EWL, Song Y, Chen J, Xu X, Wang J, Chen K, Gao J and Wang Y: The transcription factor Rpn4 activates its own transcription and induces efflux pump expression to confer fluconazole resistance in Candida auris. mBio. 14:e02688–e02623. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Garcia A, Huh EY and Lee SC: Serine/Threonine phosphatase calcineurin orchestrates the intrinsic resistance to micafungin in the human-pathogenic fungus mucor circinelloides. Antimicrob Agents Chemother. 67:e00686–e00622. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Al-Hatmi AMS, Meis JF and de Hoog GS: Fusarium: Molecular diversity and intrinsic drug resistance. PLoS Pathog. 12:e10054642016. View Article : Google Scholar : PubMed/NCBI | |
|
Delarze E and Sanglard D: Defining the frontiers between antifungal resistance, tolerance and the concept of persistence. Drug Resist Updat. 23:12–19. 2015. View Article : Google Scholar | |
|
Arastehfar A, Lass-Flörl C, Garcia-Rubio R, Daneshnia F, İlkit M, Boekhout T, Gabaldon T and Perlin DS: The quiet and underappreciated rise of drug-resistant invasive fungal pathogens. J Fungi (Basel). 6:1382020. View Article : Google Scholar : PubMed/NCBI | |
|
Delarze E, Brandt L, Trachsel E, Patxot M, Pralong C, Maranzano F, Chauvel M, Legrand M, Znaidi S, Bougnoux ME, et al: Identification and characterization of mediators of fluconazole tolerance in Candida albicans. Front Microbiol. 11:5911402020. View Article : Google Scholar | |
|
Koohi SR, Shankarnarayan SA, Galon CM and Charlebois DA: Identification and elimination of antifungal tolerance in Candida auris. Biomedicines. 11:8982023. View Article : Google Scholar : PubMed/NCBI | |
|
Delma FZ, Melchers WJG, Verweij PE and Buil JB: Wild-type MIC distributions and epidemiological cutoff values for 5-flucytosine and Candida species as determined by EUCAST broth microdilution. JAC Antimicrob Resist. 6:dlae1532024. View Article : Google Scholar | |
|
Pfaller MA, Boyken L, Hollis RJ, Kroeger J, Messer SA, Tendolkar S, Jones RN, Turnidge J and Diekema DJ: Wild-type MIC distributions and epidemiological cutoff values for the echinocandins and Candida spp. J Clin Microbiol. 48:52–56. 2010. View Article : Google Scholar | |
|
Espinel-Ingroff A, Colombo AL, Cordoba S, Dufresne PJ, Fuller J, Ghannoum M, Gonzalez GM, Guarro J, Kidd SE, Meis JF, et al: International evaluation of MIC distributions and epidemiological cutoff value (ECV) definitions for fusarium species identified by molecular methods for the CLSI broth microdilution method. Antimicrob Agents Chemother. 60:1079–1084. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Levinson T, Dahan A, Novikov A, Paran Y, Berman J and Ben-Ami R: Impact of tolerance to fluconazole on treatment response in Candida albicans bloodstream infection. Mycoses. 64:78–85. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Yu S, Paderu P, Lee A, Eirekat S, Healey KR, Chen L, Perlin DS and Zhao Y: Histone acetylation regulator Gcn5 mediates drug resistance and virulence of Candida Glabrata. Microbiol Spectr. 10:e00963222022. View Article : Google Scholar : PubMed/NCBI | |
|
Garnaud C, García-Oliver E, Wang Y, Maubon D, Bailly S, Despinasse Q, Champleboux M, Govin J and Cornet M: The rim pathway mediates antifungal tolerance in Candida albicans through newly identified Rim101 transcriptional targets, including Hsp90 and Ipt1. Antimicrob Agents Chemother. 62:e01785–e01717. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Wiederhold NP: Antifungal resistance: Current trends and future strategies to combat. Infect Drug Resist. 10:249–259. 2017. View Article : Google Scholar | |
|
Lestrade PPA, Buil JB, van Der Beek MT, Kuijper EJ, van Dijk K, Kampinga GA, Rijnders BJA, Vonk AG, de Greeff SC, Schoffelen AF, et al: Paradoxal trends in azole-resistant Aspergillus fumigatus in a national multicenter surveillance program, the Netherlands, 2013–2018. Emerg Infect Dis. 26:1447–1455. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Edwards HM and Rhodes J: Accounting for the biological complexity of pathogenic fungi in phylogenetic dating. J Fungi (Basel). 7:6612021. View Article : Google Scholar : PubMed/NCBI | |
|
White TC, Marr KA and Bowden RA: Clinical, cellular, and molecular factors that contribute to antifungal drug resistance. Clin Microbiol Re. 11:382–402. 1998. View Article : Google Scholar | |
|
Gladyshev E: Repeat-Induced Point Mutation and Other Genome Defense Mechanisms in Fungi. Microbiol Spectr. 5:102017. View Article : Google Scholar | |
|
Hane JK, Williams AH, Taranto AP, Solomon PS and Oliver RP: Repeat-induced point mutation: A fungal-specific, endogenous mutagenesis process. Genet Transform Syst Fungi. 2:55–68. 2015. View Article : Google Scholar | |
|
Xiang MJ, Liu JY, Ni PH, Wang S, Shi C, Wei B, Ni YX and Ge HL: Erg11 mutations associated with azole resistance in clinical isolates of Candida albicans. FEMS Yeast Res. 13:386–393. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Biswas C, Marcelino VR, Van Hal S, Halliday C, Martinez E, Wang Q, Kidd S, Kennedy K, Marriott D, Morrissey CO, et al: Whole genome sequencing of Australian Candida glabrata isolates reveals genetic diversity and novel sequence types. Front Microbiol. 9:29462018. View Article : Google Scholar | |
|
Rocha EMF, Garcia-Effron G, Park S and Perlin DS: A Ser678Pro substitution in Fks1p confers resistance to echinocandin drugs in Aspergillus fumigatus. Antimicrob Agents Chemother. 51:4174–4176. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Lackner M, Tscherner M, Schaller M, Kuchler K, Mair C, Sartori B, Istel F, Arendrup MC and Lass-Flörl C: Positions and numbers of FKS mutations in Candida albicans selectively influence in vitro and in vivo susceptibilities to echinocandin treatment. Antimicrob Agents Chemother. 58:3626–3635. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Diaz-Guerra TM, Mellado E, Cuenca-Estrella M and Rodriguez-Tudela JL: A point mutation in the 14α-Sterol demethylase gene cyp51A contributes to itraconazole resistance in Aspergillus fumigatus. Antimicrob Agents Chemother. 47:1120–1124. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Katiyar SK, Alastruey-Izquierdo A, Healey KR, Johnson ME, Perlin DS and Edlind TD: Fks1 and Fks2 are functionally redundant but differentially regulated in Candida glabrata: Implications for echinocandin resistance. Antimicrob Agents Chemother. 56:6304–6309. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Katiyar SK, Alastruey-Izquierdo A, Healey KR, Johnson ME, Perlin DS and Edlind TD: Contribution of clinically derived mutations in ERG11 to azole resistance in Candida albicans. Antimicrob Agents Chemother. 59:450–460. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Wirsching S, Moran GP, Sullivan DJ, Coleman DC and Morschhäuser J: MDR1-mediated drug resistance in Candida dubliniensis. Antimicrob Agents Chemother. 45:3416–3421. 2001. View Article : Google Scholar : PubMed/NCBI | |
|
Morschhäuser J, Barker KS, Liu TT, Blaß-Warmuth J, Homayouni R and Rogers PD: The transcription factor Mrr1p controls expression of the MDR1 efflux pump and mediates multidrug resistance in Candida albicans. PLoS Pathog. 3:e1642007. View Article : Google Scholar | |
|
Abbes S, Mary C, Sellami H, Michel-Nguyen A, Ayadi A and Ranque S: Interactions between copy number and expression level of genes involved in fluconazole resistance in Candida glabrata. Front Cell Infect Microbiol. 3:742013. View Article : Google Scholar | |
|
Rajasingham R, Smith RM, Park BJ, Jarvis JN, Govender NP, Chiller TM, Denning DW, Loyse A and Boulware DR: Global burden of disease of HIV-associated cryptococcal meningitis: An updated analysis. Lancet Infect Dis. 17:873–881. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Priest SJ, Yadav V, Roth C, Dahlmann TA, Kück U, Magwene PM and Heitman J: Uncontrolled transposition following RNAi loss causes hypermutation and antifungal drug resistance in clinical isolates of Cryptococcus neoformans. Nat Microbiol. 7:1239–1251. 2022. View Article : Google Scholar | |
|
Torres EM, Sokolsky T, Tucker CM, Chan LY, Boselli M, Dunham MJ and Amon A: Effects of aneuploidy on cellular physiology and cell division in haploid yeast. Science. 317:916–924. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Williams BR, Prabhu VR, Hunter KE, Glazier CM, Whittaker CA, Housman DE and Amon A: Aneuploidy affects proliferation and spontaneous immortalization in mammalian cells. Science. 322:703–709. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Tsai HJ and Nelliat A: A double-edged sword: Aneuploidy is a prevalent strategy in fungal adaptation. Genes (Basel). 10:7872019. View Article : Google Scholar : PubMed/NCBI | |
|
Selmecki A, Forche A and Berman J: Aneuploidy and isochromosome formation in drug-resistant Candida albicans. Science. 313:367–370. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Ji H, Zhang W, Zhou Y, Zhang M, Zhu J, Song Y and Lü J: A three-dimensional model of lanosterol 14α-demethylase of Candida albicans and its interaction with azole antifungals. J Med Chem. 43:2493–2505. 2000. View Article : Google Scholar : PubMed/NCBI | |
|
Coste AT, Karababa M, Ischer F, Bille J and Sanglard D: TAC1, transcriptional activator of CDR genes, is a new transcription factor involved in the regulation of Candida albicans ABC transporters CDR1 and CDR2. Eukaryot Cell. 3:1639–1652. 2004. View Article : Google Scholar | |
|
Selmecki AM, Dulmage K, Cowen LE, Anderson JB and Berman J: Acquisition of aneuploidy provides increased fitness during the evolution of antifungal drug resistance. PLOS Genet. 5:e10007052009. View Article : Google Scholar | |
|
Ford CB, Funt JM, Abbey D, Issi L, Guiducci C, Martinez DA, Delorey T, Li BY, White TC, Cuomo C, et al: The evolution of drug resistance in clinical isolates of Candida albicans. Elife. 4:e006622015. View Article : Google Scholar : PubMed/NCBI | |
|
Mackey AI, Fillinger RJ, Hendricks PS, Thomson GJ, Cuomo CA, Bennett RJ and Anderson MZ: Aneuploidy confers a unique transcriptional and phenotypic profile to Candida albicans. Nat Commun. 16:32872025. View Article : Google Scholar : PubMed/NCBI | |
|
Sun LL, Li H, Yan TH, Fang T, Wu H, Cao YB, Lu H, Jiang YY and Yang F: Aneuploidy mediates rapid adaptation to a subinhibitory amount of fluconazole in Candida albicans. Microbiol Spectr. 11:e03016–e03022. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Sionov E, Lee H, Chang YC and Kwon-Chung KJ: Cryptococcus neoformans overcomes stress of azole drugs by formation of disomy in specific multiple chromosomes. PLoS Pathog. 6:e10008482010. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang Z, Sun L, Fu B, Deng J, Jia C, Miao M, Yang F, Cao YB and Yan TH: Aneuploidy underlies brefeldin A-induced antifungal drug resistance in Cryptococcus neoformans. Front Cell Infect Microbiol. 14:13977242024. View Article : Google Scholar | |
|
Hu G, Wang J, Choi J, Jung WH, Liu I, Litvintseva AP, Bicanic T, Aurora R, Mitchell TG, Perfect JR and Kronstad JW: Variation in chromosome copy number influences the virulence of Cryptococcus neoformans and occurs in isolates from AIDS patients. BMC Genomics. 12:1–19. 2011. View Article : Google Scholar | |
|
Sasse C, Dunkel N, Schäfer T, Schneider S, Dierolf F, Ohlsen K and Morschhäuser J: The stepwise acquisition of fluconazole resistance mutations causes a gradual loss of fitness in andida albicans. Mol Microbiol. 86:539–556. 2012. View Article : Google Scholar | |
|
Heil CS: Loss of heterozygosity and its importance in evolution. J Mol Evol. 91:369–377. 2023. View Article : Google Scholar | |
|
Forche A, Abbey D, Pisithkul T, Weinzierl MA, Ringstrom T, Bruck D, Petersen K and Berman J: Stress alters rates and types of loss of heterozygosity in Candida albicans. mBio. 2:e00129–e00111. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Bennett RJ, Forche A and Berman J: Rapid mechanisms for generating genome diversity: Whole ploidy shifts, aneuploidy, and loss of heterozygosity. Cold Spring Harb Perspect Med. 4:a0196042014. View Article : Google Scholar : PubMed/NCBI | |
|
White TC: Increased mRNA levels of ERG16, CDR, and MDR1 correlate with increases in azole resistance in Candida albicans isolates from a patient infected with human immunodeficiency virus. Antimicrob Agents Chemother. 41:1482–1487. 1997. View Article : Google Scholar : PubMed/NCBI | |
|
Luna-Tapia A, Willems HME, Parker JE, Tournu H, Barker KS, Nishimoto AT, Rogers PD, Kelly SL, Peters BM and Palmer GE: Loss of Upc2p-inducible ERG3 transcription is sufficient to confer niche-specific azole resistance without compromising Candida albicans pathogenicity. mBio. 9:e00225–e00218. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Rustad TR, Stevens DA, Pfaller MA and White TC: Homozygosity at the Candida albicans MTL locus associated with azole resistance. Microbiology. 148:1061–1072. 2002. View Article : Google Scholar : PubMed/NCBI | |
|
Gambhir N, Harris SD and Everhart SE: Evolutionary significance of fungal hypermutators: Lessons learned from clinical strains and implications for fungal plant pathogens. mSphere. 7:e00087–e00022. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Healey KR, Ortigosa CJ, Shor E and Perlin DS: Genetic drivers of multidrug resistance in Candida glabrata. Front Microbiol. 7:19952016. View Article : Google Scholar | |
|
Healey KR, Zhao Y, Perez WB, Lockhart SR, Sobel JD, Farmakiotis D, Kontoyiannis DP, Sanglard D, Taj-Aldeen SJ, Alexander BD, et al: Prevalent mutator genotype identified in fungal pathogen Candida glabrata promotes multi-drug resistance. Nat Commun. 7:111282016. View Article : Google Scholar : PubMed/NCBI | |
|
Helmstetter N, Chybowska AD, Delaney C, Da Silva Dantas A, Gifford H, Wacker T, Munro C, Warris A, Jones B, Cuomo CA, et al: Population genetics and microevolution of clinical Candida glabrata reveals recombinant sequence types and hyper-variation within mitochondrial genomes, virulence genes, and drug targets. Genetics. 221:iyac0312022. View Article : Google Scholar : PubMed/NCBI | |
|
Vale-Silva L, Beaudoing E, Tran VDT and Sanglard D: Comparative genomics of two sequential Candida glabrata clinical isolates. G3 (Bethesda). 7:2413–2426. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Boyce KJ, Wang Y, Verma S, Shakya VPS, Xue C and Idnurm A: Mismatch repair of DNA replication errors contributes to microevolution in the pathogenic fungus Cryptococcus neoformans. mBio. 8:e00595–e00517. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Dos Reis TF, Silva LP, de Castro PA, do Carmo RA, Marini MM, da Silveira JF, Ferreira BH, Rodrigues F, Lind AL, Rokas A and Goldman GH: The Aspergillus fumigatus mismatch repair MSH2 homolog is important for virulence and azole resistance. mSphere. 4:e00416–e00419. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Ke W, Xie Y, Chen Y, Ding H, Ye L, Qiu H, Li H, Zhang L, Chen L, Tian X, et al: Fungicide-tolerant persister formation during cryptococcal pulmonary infection. Cell Host Microbe. 32:276–289. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Silva S, Rodrigues CF, Araújo D, Rodrigues ME and Henriques M: Candida Species Biofilms' antifungal resistance. J Fungi (Basel). 3:82017. View Article : Google Scholar : PubMed/NCBI | |
|
Massey J, Zarnowski R and Andes D: Role of the extracellular matrix in Candida biofilm antifungal resistance. FEMS Microbiol Rev. 47:fuad0592023. View Article : Google Scholar : PubMed/NCBI | |
|
Hommel B, Sturny-Leclère A, Volant S, Veluppillai N, Duchateau M, Yu CH, Hourdel V, Varet H, Matondo M, Perfect JR, et al: Cryptococcus neoformans resists to drastic conditions by switching to viable but non-culturable cell phenotype. PLoS Pathog. 15:e10079452019. View Article : Google Scholar : PubMed/NCBI | |
|
Alanio A, Vernel-Pauillac F, Sturny-Leclère A and Dromer F, Alanio A, Vernel-Pauillac F and Dromer F: Cryptococcus neoformans host adaptation: Toward biological evidence of dormancy. mBio. 6:e02580–e02514. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Hayes BME, Anderson MA, Traven A, van der Weerden NL and Bleackley MR: Activation of stress signalling pathways enhances tolerance of fungi to chemical fungicides and antifungal proteins. Cell Mol life Sci. 71:2651–2666. 2014. View Article : Google Scholar | |
|
Cruz MC, Goldstein AL, Blankenship JR, Del Poeta M, Davis D, Cardenas ME, Perfect JR, McCusker JH and Heitman J: Calcineurin is essential for survival during membrane stress in Candida albicans. EMBO J. 21:546–559. 2002. View Article : Google Scholar : PubMed/NCBI | |
|
LaFleur MD, Kumamoto CA and Lewis K: Candida albicans biofilms produce antifungal-tolerant persister cells. Antimicrob Agents Chemother. 50:3839–3846. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Fréalle E, Aliouat-Denis CM, Delhaes L, Hot D and Dei-Cas E: Transcriptomic insights into the oxidative response of stress-exposed Aspergillus fumigatus. Curr Pharm Des. 19:3713–3737. 2013. View Article : Google Scholar | |
|
Chang Z, Yadav V, Lee SC and Heitman J: Epigenetic mechanisms of drug resistance in fungi. Fungal Genet Biol. 132:1032532019. View Article : Google Scholar | |
|
Brandao FAS, Derengowski LS, Albuquerque P, Nicola AM, Silva-Pereira I and Poças-Fonseca MJ: Histone deacetylases inhibitors effects on Cryptococcus neoformans major virulence phenotypes. Virulence. 6:618–630. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Brandão F, Esher SK, Ost KS, Pianalto K, Nichols CB, Fernandes L, Bocca AL, Poças-Fonseca MJ and Alspaugh JA: HDAC genes play distinct and redundant roles in Cryptococcus neoformans virulence. Sci Rep. 8:52092018. View Article : Google Scholar | |
|
Ranjan K, Brandão F, Morais JAV, Muehlmann LA, Silva-Pereira I, Bocca AL, Matos LF and Poças-Fonseca MJ: The role of Cryptococcus neoformans histone deacetylase genes in the response to antifungal drugs, epigenetic modulators and to photodynamic therapy mediated by an aluminium phthalocyanine chloride nanoemulsion in vitro. J Photochem Photobiol B. 216:1121312021. View Article : Google Scholar : PubMed/NCBI | |
|
Nobile CJ, Fox EP, Nett JE, Sorrells TR, Mitrovich QM, Hernday AD, Tuch BB, Andes DR and Johnson AD: A recently evolved transcriptional network controls biofilm development in Candida albicans. Cell. 148:126–138. 2012. View Article : Google Scholar | |
|
Uppuluri P, Pierce CG, Thomas DP, Bubeck SS, Saville SP and Lopez-Ribot JL: The transcriptional regulator Nrg1p controls Candida albicans biofilm formation and dispersion. Eukaryot Cell. 9:1531–1537. 2010. View Article : Google Scholar | |
|
Li X, Cai Q, Mei H, Zhou X, Shen Y, Li D and Liu W: The Rpd3/Hda1 family of histone deacetylases regulates azole resistance in Candida albicans. J Antimicrob Chemother. 70:1993–2003. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Freitag M: Histone methylation by SET domain proteins in fungi. Annu Rev Microbiol. 71:413–439. 2017. View Article : Google Scholar | |
|
Honda S, Bicocca VT, Gessaman JD, Rountree MR, Yokoyama A, Yu EY, Selker JM and Selker EU: Dual chromatin recognition by the histone deacetylase complex HCHC is required for proper DNA methylation in Neurospora crassa. Proc Natl Acad Sci USA. 113:E6135–E6144. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Nai YS, Huang YC, Yen MR and Chen PY: Diversity of fungal DNA methyltransferases and their association with DNA methylation patterns. Front Microbiol. 11:6169222021. View Article : Google Scholar | |
|
Jeon J, Choi J, Lee GW, Park SY, Huh A, Dean RA and Lee YH: Genome-wide profiling of DNA methylation provides insights into epigenetic regulation of fungal development in a plant pathogenic fungus, Magnaporthe oryzae. Sci Rep. 5:85672015. View Article : Google Scholar : PubMed/NCBI | |
|
Catania S, Dumesic PA, Pimentel H, Nasif A, Stoddard CI, Burke JE, Diedrich JK, Cook S, Shea T, Geinger E, et al: Evolutionary persistence of DNA methylation for millions of years after ancient loss of a de novo methyltransferase. Cell. 180:263–277. 2020. View Article : Google Scholar | |
|
Baker KM, Hoda S, Saha D, Gregor JB, Georgescu L, Serratore ND, Zhang Y, Cheng L, Lanman NA, Briggs SD, et al: The Set1 histone H3K4 methyltransferase contributes to azole susceptibility in a species-specific manner by differentially altering the expression of drug efflux pumps and the ergosterol gene pathway. Antimicrob Agents Chemother. 66:e02250–e02221. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Khemiri I, Tebbji F, Burgain A and Sellam A: Regulation of copper uptake by the SWI/SNF chromatin remodeling complex in Candida albicans affects susceptibility to antifungal and oxidative stresses under hypoxia. FEMS Yeast Res. 24:foae0182024. View Article : Google Scholar : PubMed/NCBI | |
|
Salem-Bango Z, Price TK, Chan JL, Chandrasekaran S, Garner OB and Yang S: Fungal whole-genome sequencing for species identification: From test development to clinical utilization. J Fungi (Basel). 9:1832023. View Article : Google Scholar : PubMed/NCBI | |
|
Jiang S, Chen Y, Han S, Lv L and Li L: Next-generation sequencing applications for the study of fungal pathogens. Microorganisms. 10:18822022. View Article : Google Scholar : PubMed/NCBI | |
|
Liu SY, Lin JQ, Wu HL, Wang CC, Huang SJ, Luo YF, Sun JH, Zhou JX, Yan SJ, He JG, et al: Bisulfite sequencing reveals that Aspergillus flavus holds a hollow in DNA methylation. PLoS One. 7:e303492012. View Article : Google Scholar : PubMed/NCBI | |
|
Tan K and Wong KH: RNA polymerase II ChIP-seq-a powerful and highly affordable method for studying fungal genomics and physiology. Biophys Rev. 11:79–82. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Roemer T and Krysan DJ: Antifungal drug development: Challenges, unmet clinical needs, and new approaches. Cold Spring Harb Perspect Med. 4:a0197032014. View Article : Google Scholar : PubMed/NCBI | |
|
Fisher MC, Alastruey-Izquierdo A, Berman J, Bicanic T, Bignell E, Bowyer P, Bromley M, Brüggemann R, Garber G, Cornely OA, et al: Tackling the emerging threat of antifungal resistance to human health. Nat Rev Microbiol. 20:557–571. 2022. View Article : Google Scholar | |
|
Grand View Research, . Antifungal drugs market size, share & growth report 2030 [Internet]. 2025.Available from:. https://www.grandviewresearch.com/industry-analysis/antifungal-drugs-market | |
|
Pyrpasopoulou A, Iosifidis E, Antachopoulos C and Roilides E: Antifungal drug dosing adjustment in critical patients with invasive fungal infections. J Emerg Crit Care Med. 3:10.21037/jeccm.2019.08.01. 2019. View Article : Google Scholar | |
|
Baracaldo-Santamaría D, Cala-Garcia JD, Medina-Rincón GJ, Rojas-Rodriguez LC and Calderon-Ospina CA: Therapeutic drug monitoring of antifungal agents in critically ill patients: Is there a need for dose optimisation? Antibiotics (Basel). 11:6452022. View Article : Google Scholar | |
|
Glampedakis E, Coste AT, Aruanno M, Bachmann D, Delarze E, Erard V and Lamoth F: Efficacy of antifungal monotherapies and combinations against Aspergillus calidoustus. Antimicrob Agents Chemother. 62:e01137–e01118. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Rieger CT, Ostermann H, Kolb HJ, Fiegl M, Huppmann S, Morgenstern N and Tischer J: A clinical cohort trial of antifungal combination therapy: Efficacy and toxicity in haematological cancer patients. Ann Hematol. 87:915–922. 2008. View Article : Google Scholar | |
|
Candoni A, Caira M, Cesaro S, Busca A, Giacchino M, Fanci R, Delia M, Nosari A, Bonini A, Cattaneo C, et al: Multicentre surveillance study on feasibility, safety and efficacy of antifungal combination therapy for proven or probable invasive fungal diseases in haematological patients: the SEIFEM real-life combo study. Mycoses. 57:342–350. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Tu B, Yin G and Li H: Synergistic effects of vorinostat (SAHA) and azoles against Aspergillus species and their biofilms. BMC Microbiol. 20:1–7. 2020. View Article : Google Scholar | |
|
Rodrigues CF, Alves DF and Henriques M: Combination of Posaconazole and Amphotericin B in the treatment of Candida glabrata biofilms. Microorganisms. 6:1232018. View Article : Google Scholar : PubMed/NCBI | |
|
Vitale RG: Role of antifungal combinations in difficult to treat Candida infections. J Fungi (Basel). 7:7312021. View Article : Google Scholar : PubMed/NCBI | |
|
Fernandes CM, Dasilva D, Haranahalli K, McCarthy JB, Mallamo J, Ojima I and Del Poeta M: The future of antifungal drug therapy: Novel compounds and targets. Antimicrob Agents Chemother. 65:e01719–e01720. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Hodges MR, Tawadrous M, Cornely OA, Thompson GR III, Slavin MA, Maertens JA, Dadwal SS, Rahav G, Hazel S, Almas M, et al: Fosmanogepix for the treatment of invasive mold diseases caused by Aspergillus species and rare molds: A phase 2, open-label study (AEGIS). Clin Infect Dis. 9:ciaf1852025. View Article : Google Scholar | |
|
Oliver JD, Sibley GEM, Beckmann N, Dobb KS, Slater MJ, McEntee L, du Pré S, Livermore J, Bromley MJ, Wiederhold NP, et al: F901318 represents a novel class of antifungal drug that inhibits dihydroorotate dehydrogenase. Proc Natl Acad Sci USA. 113:12809–12814. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Tawfik DM, Dereux C, Tremblay JA, Boibieux A, Braye F, Cazauran JB, Rabodonirina M, Cerrato E, Guichard A, Venet F, et al: Interferon gamma as an immune modulating adjunct therapy for invasive mucormycosis after severe burn-A case report. Front Immunol. 13:8836382022. View Article : Google Scholar | |
|
Albahar F, Alhamad H, Assab MA, Abu-Farha R, Alawi L and Khaleel S: The impact of antifungal stewardship on clinical and performance measures: A global systematic review. Trop Med Infect Dis. 9:82023. View Article : Google Scholar : PubMed/NCBI | |
|
Kühbacher A, Birch M, Oliver JD and Gsaller F: Anti-Aspergillus activities of olorofim at sub-MIC levels during early-stage growth. Microbiol Spectr. 12:e03304–e03323. 2024. View Article : Google Scholar | |
|
Rhein J, Hullsiek KH, Tugume L, Nuwagira E, Mpoza E, Evans EE, Kiggundu R, Pastick KA, Ssebambulidde K, Akampurira A, et al: Adjunctive sertraline for HIV-associated cryptococcal meningitis: A randomised, placebo-controlled, double-blind phase 3 trial. Lancet Infect Dis. 19:843–851. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Liu Q, Guo X, Jiang G, Wu G, Miao H, Liu K, Chen S, Sakamoto N, Kuno T, Yao F and Fang Y: NADPH-cytochrome P450 reductase Ccr1 is a target of tamoxifen and participates in its antifungal activity via regulating cell wall integrity in fission yeast. Antimicrob Agents Chemother. 64:e00079–e00072. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Dai X, Liu X, Li J, Chen H, Yan C, Li Y, Liu H, Deng D and Wang X: Structural insights into the inhibition mechanism of fungal GWT1 by manogepix. Nat Commun. 15:91942024. View Article : Google Scholar : PubMed/NCBI | |
|
Schwebke JR, Sobel R, Gersten JK, Sussman SA, Lederman SN, Jacobs MA, Chappell BT, Weinstein DL, Moffett AH, Azie NE, et al: Ibrexafungerp versus placebo for vulvovaginal candidiasis treatment: A phase 3, randomized, controlled superiority trial (VANISH 303). Clin Infect Dis. 74:1979–1985. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
(FDA) USF and DA, . Drug trials snapshots: brexafemme [Internet]. FDA; 2023, Available from:. https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshots-brexafemme | |
|
Firooz A, Nafisi S and Maibach HI: Novel drug delivery strategies for improving econazole antifungal action. Int J Pharm. 495:599–607. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Nami S, Aghebati-Maleki A and Aghebati-Maleki L: Current applications and prospects of nanoparticles for antifungal drug delivery. EXCLI J. 20:562–584. 2021.PubMed/NCBI | |
|
Stone NRH, Bicanic T, Salim R and Hope W: Liposomal amphotericin B (AmBisome®): A review of the pharmacokinetics, pharmacodynamics, clinical experience and future directions. Drugs. 76:485–500. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Jarvis JN, Lawrence DS, Meya DB, Kagimu E, Kasibante J, Mpoza E, Rutakingirwa MK, Ssebambulidde K, Tugume L, Rhein J, et al: Single-dose liposomal amphotericin B treatment for cryptococcal meningitis. N Engl J Med. 386:1109–1120. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Empitu MA, Kadariswantiningsih IN and Shakri NM: Pharmacological strategies for targeting biofilms in otorhinolaryngologic infections and overcoming antimicrobial resistance. Biomed Rep. 22:952025. View Article : Google Scholar : PubMed/NCBI | |
|
Vera-González N, Bailey-Hytholt CM, Langlois L, de Camargo Ribeiro F, de Souza Santos EL, Junqueira JC and Shukla A: Anidulafungin liposome nanoparticles exhibit antifungal activity against planktonic and biofilm Candida albicans. J Biomed Mater Res Part A. 108:2263–2276. 2020. View Article : Google Scholar | |
|
El-Housiny S, Eldeen MA, El-Attar YA, Salem HA, Attia D, Bendas ER and El-Nabarawi MA: Fluconazole-loaded solid lipid nanoparticles topical gel for treatment of pityriasis versicolor: Formulation and clinical study. Drug Deliv. 25:78–90. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Raad I, Mohamed JA, Reitzel RA, Jiang Y, Raad S, Al Shuaibi M, Chaftari AM and Hachem RY: Improved antibiotic-impregnated catheters with extended-spectrum activity against resistant bacteria and fungi. Antimicrob Agents Chemother. 56:935–941. 2012. View Article : Google Scholar : PubMed/NCBI |
