Chapter 2. New Aspects of Candida spp Infections


Fatemeh Nikoomanesh1,2, Maryam Roudbaryand Farhad Saeif4
1Department of Medical Microbiology, School of Medicine, Birjand University of Medical Sciences,
Birjand, Iran
2Infectious Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
3Deapartment of Parasitology and Mycology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
4Department of Immunology and Allergy, Academic Center for Education, Culture, and Research (ACECR), Tehran, Iran

Part of the book: The Book of Fungal Pathogens


Candidiasis is an opportunistic fungal infection resulting from an imbalance between the host immune system and crucial virulence factors of Candida species. The Candida spp., are one of the major constituents of the human mycobiome as well as the main cause of invasive fungal infections, particularly in immunocompromised patients. They affect the cases who consume a wide-spectrum antibiotic/steroid and those who have prolonged ICU stays and central venous catheters, transplant patients, chemotherapy/ radiotherapy, patients under invasive or noninvasive ventilation, and diabetic individuals with high-rate mortality. In recent decades, Candida species are considered the fourth cause of bloodstream infections; however, the epidemiology of candidemia has been linked to different geographical areas. On the other hand, the emergence of multidrug-resistant Candida spp. named Candia auris, as a global challenge in different countries over recent years in the world, leads to lethal as well as invasive infections with a high rate of spread among patients. At the beginning of the novel coronavirus disease 2019 (COVID-19) pandemic with causative agent of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), invasive yeast infections (IYFs), especially Candidiasis, are dramatically increasing in those individuals as the major groups under immunosuppressed condition. Although echinocandins and azoles are the most common antifungals used for the treatment of IYFs, the increased therapeutic failures exerted by multidrug-resistant Candida spp. such as C. auris and C. glabrata, calling for the discovery of novel antifungal agents with therapeutic approaches seems necessary. Here, we attempt to focus on the acquisition of knowledge associated with pathogenicity of Candida spp., particularly the indispensable role of virulence factors (germination, adherence, biofilm formation, phospholipase and proteinase production), genes that contribute to drug resistance and the related mechanisms, new therapeutic strategies for the treatment of Candidiasis includes combination therapies, application of biomaterials for drug delivery, antibodies, and vaccination, photodynamic therapy, probiotics, and new antifungal products to overcome Candida infections.

Keywords: Candida spp., virulence factors, multidrug-resistance, new therapeutic strategies


[1] Talapko J, Juzbašić M, Matijević T, Pustijanac E, Bekić S, Kotris I, Škrlec I. Candida albicans-the
virulence factors and clinical manifestations of infection. J Fungi. 2021;7(2):1–19. Available from:
[2] Pfaller MA, Diekema DJ, Gibbs DL, Newell VA, Ellis D, Tullio V, Rodloff, A. Fu, W. Ling, TA.
Results from the artemis disk global antifungal surveillance study, 1997 to 2007: A 10.5-year analysis
of susceptibilities of Candida species to fluconazole and voriconazole as determined by CLSI
standardized disk diffusion. J Clin Microbiol. 2010;48(4):1366–77. Available from:
[3] Morad HOJ, Wild AM, Wiehr S, Davies G, Maurer A, Pichler BJ, Thornton C. pre-clinical imaging of
invasive candidiasis using immunoPET/MR. Front Microbiol. 2018 Aug 23;9(AUG):1996.
[4] Pappas PG, Lionakis MS, Arendrup MC, Ostrosky-Zeichner L, Kullberg BJ. Invasive candidiasis. Nat
Rev Dis Prim. 2018;4(1):1–20. Available from:
[5] Ciurea CN, Kosovski IB, Mare AD, Toma F, Pintea-Simon IA, Man A. Candida and candidiasis—
opportunism versus pathogenicity: A review of the virulence traits. Microorganisms, 2020. p. 1–17.
Available from:
[6] Yoo YJ, Kim AR, Perinpanayagam H, Han SH, Kum KY. Candida albicans virulence factors and
pathogenicity for endodontic infections. Microorganisms, 2020. p. 1–18. Available from:
[7] Yapar N. Epidemiology and risk factors for invasive candidiasis. Ther Clin Risk Manag.
2014;10(1):95–105. Available from:
[8] Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP, Edmond MB. Nosocomial bloodstream
infections in US hospitals: Analysis of 24,179 cases from a prospective nationwide surveillance study.
Clin Infect Dis. 2004;39(3):309–17. Available from: https://pubmed.ncbi.
[9] Kotey FC, Dayie NT, Tetteh-Uarcoo PB, Donkor ES. Candida Bloodstream Infections: Changes in
Epidemiology and Increase in Drug Resistance. Infect Dis Res Treat. 2021;14:117863372110269.
Available from:
[10] Lockhart SR, Iqbal N, Cleveland AA, Farley MM, Harrison LH, Bolden CB, Baughman W, Stein B,
Hollick R, Park B, Chiller T. Species identification and antifungal susceptibility testing of Candida
bloodstream isolates from population-based surveillance studies in two U.S. cities from 2008 to 2011.
J Clin Microbiol. 2012;50(11):3435–42. Available from:
[11] Orasch C, Marchetti O, Garbino J, Schrenzel J, Zimmerli S, Mühlethaler K, Pfyffer G, Ruef C, Fehr J,
Zbinden R, Calandra T, Bille J, Bregenzer T, Conen A, Fankhauser H, Fluchger U, Khanna N, Frei R,
Heininger U, Hertel R, Franciollo M, Giovanni O, Dolina M, Rothen M, Dubuis O, Tarr P, Graf S,
Fleisch F, Risch M, Ritzler E, Chuard C, erard V, Fracheboud D, Emonet S, Genne D, Lienhardt R,
Chave J, Andreutti-Zaugg C, Gallusser A, Graber P, Monotti R, Regionale O, Bernasconi E, Civico O,
Krause M, Herzog K, Piso R, Schibli U, Bally F, Troillet N, Tissiere L, Boggian K, Bruderer T, Gubler
J, Eich G, Berger . Candida species distribution and antifungal susceptibility testing according to
European Committee on Antimicrobial Susceptibility Testing and new vs.
old Clinical and Laboratory Standards Institute clinical breakpoints:
A 6-year prospective candidaemia s. Clin Microbiol Infect. 2014;20(7):698–705.
[12] Pfaller MA, Moet GJ, Messer SA, Jones RN, Castanheira M. Candida Bloodstream Infections:
Comparison of Species Distributions and Antifungal Resistance Patterns in Community-Onset and
Nosocomial Isolates in the SENTRY Antimicrobial Surveillance Program, 2008-2009. Antimicrob
Agents Chemother. 2011;55(2):561. Available from: /pmc/articles/PMC3028787/.
[13] Aldardeer NF, Albar H, Al-Attas M, Eldali A, Qutub M, Hassanien A, Alraddadi B. Antifungal
resistance in patients with Candidaemia: A retrospective cohort study.
BMC Infect Dis. 2020 Jan 17;20(1):1–7. Available from:
[14] Macphail GL, Taylor GD, Buchanan-Chell M, Ross C, WilsonS, Kureishi A.
Epidemiology, treatment and outcome of candidemia: a five-year review at three Canadian hospitals.
Mycoses. 2002;45(5–6):141–5.
[15] Pfaller MA, Diekema DJ, Gibbs DL, Newell VA, Ellis D, Tullio V, Rodloff A, Fu W, Ling TA. Global
Antifungal Surveillance Group. Results from the ARTEMIS DISK global antifungal surveillance
study, 1997 to 2007: a 10.5 year analysis of susceptibilities of Candida species to fluconazole and
voriconazole as determined by CLSI standardized disk dif. J Clin Microbiol. 2010;48(4):1366–77.
[16] Pfaller MA, Neofytos D, Diekema D, Azie N, Meier-Krische H, Quan S, Hora D. Epidemiology and
outcomes of candiemia in 3648 patients: data from the Prospective Antifungal Therapy (PATH
Alliance®) registry, 2004-2008. Diagn Microbiol Infect Dis. 2012;74(4):323–31.
[17] Pfaller MA, Moet GJ, Messer SA, Jones RN, Castanheira M. Geographic variations in species
distribution and echinocandin and azole antifungal resistance rates among Candida bloodstream
infection isolates: report from the SENTRY antimicrobial surveillance program (2008–2009).
J Clin Microbiol. 2011;49(1):396–9.
[18] Cleveland AA, Farley MM, Harrison LH, Stein B, Hallick R, Lockhart SR, Magill S. Changes in
incidence and antifungal drug resistance in candidemia: Results from population_based laboratory
surveillance in Atlanta and Baltimore, 2008-2011. Clin Infect Dis. 2012;55(10):1352–61.
[19] Lockhart SR, N I, Cleveland AA, Farley MM, Harrison LH, Bolden CB, Baughman W, Stein B, Hollick
R, Park BJ, Chiller T. Species identification and antifungal susceptibility testing of Candida
bloodstream isolates from population-based surveillance studies in two US cities from 2008 to 2011.
J Clin Microbiol. 2012;50(11):3435–42.
[20] Córdoba S, Vivot W, Bosco-Borgeat ME, Taverna C, Szusz W, Murisengo O, Isla G, Davel G. Species
distribution and susceptibility profile of yeasts isolated from blood cultures: results of a multicenter
active laboratory-based surveillance study in Argentina. Rev Argent Microbiol. 2011;43(3):176–85.
[21] Nucci M, Queiroz-Telles F, Alvarado-Matute A, Tirabaschi T, Cortes J, Zurita J, Guzman-Blanco M,
Santolaya M, Thompson L, Sifuentes-Osornio J, Echevarria J, Colombo A. Latin American Invasive
Mycosis Network. Epidemiology of candidemia in Latin America: a laboratory-based survey.
PLoS One. 2013;8(3):e59373.
[22] Tortorano AM, Peman J, Bernhardt H, Klingspor L, Kibber C, Faure O, Biraghi E, Canton E,
Zimmermann K, Seaton S, Grillot R. ECMM Working Group on Candidaemia. Epidemiology of
candidaemia in Europe: results of 28-month European Confederation of Medical Mycology (ECMM)
hospital-based surveillance study. Eur J Clin Microbiol Infect Dis. 2004;23(4):317–22.
[23] Swinne D, Watelle M, Suetens C, Mertens K, Fonteyne PA, Nolard N. A one-year survey of
candidemia in Belgium in 2002. Epidemiol Infect. 2004;132(6):1175–80.
[24] Arendrup MC, Bruun B, Christensen JJ, Fuursted K, Johansetensen L, Moller J, Nielsen L, Rosenvinge
F, Roder B, Schonheyer H, Thomsen M, Truberg K. National surveillance of fungemia in Denmark
(2004 to 2009). J Clin Microbiol. 2011;49(1):325–34.
[25] Arendrup MC, Dzajic E, Jensen RH, Kjaldgaard P, Knudsen J, Kristensen L, Leitz C, Lemming L,
Nielsen L, Olesen B, Rosenvinge F, Roder B, Schonheyder H. Epidemiological changes with potential
implication for antifungal prescription recommendations for fungaemia: data from a nationwide
fungaemia surveillance programme. Clin Microbiol Infect. 2013;19(8):E343–53.
[26] Poikonen E, Lyytikäinen O, Anttila VJ, Ruutu P. Candidemia in Finland, 1995–1999.
Emerg Infect Dis. 2003;9(8):983–90.
[27] Poikonen E, Lyytikäinen O, Anttila V, Ruutu P. Secular trend in candidemia and the use of fluconazole
in Finland, 2004–2007. BMC Infect Dis. 2010;10(312).
[28] Borg-von Zepelin M, Kunz L, Rüchel R, Reichard U, Weig M, Gross U. Epidemiology and antifungal
susceptibilities of Candida spp. to six antifungal agents: Results from a surveillance study on
fungaemia in Germany from July 2004 to August 2005. J Antimicrob Chemother. 2007;60(2):424–8.
[29] Meyer E, Geffers C, Gastmeier P, Schwab F. No increase in primary nosocomial candidemia in 682
German intensive care units during 2006 to 2011. Euro Surveill. 2013;18(24).
[30] Montagna MT, Caggiano G, Lovero G,. De Giglio O, Coretti C, Cuna T, Latta R, Giglio M, Dalfino L,
Bruno F Puntillo F. Epidemiology of invasive fungal infections in the intensive care unit: Results of a
multicenter Italian survey (AURORA Project). Infection. 2013;41(3):645–53.
[31] Tortorano AM, Prigitano A, Lazzarini C, Passera M, Deiana M, Cavinto S, De Luca C, Grancini A, lo
Cascio G, Ossi C, Sala E, Montagna M. A 1-year prospective survey of candidemia in Italy and
changing epidemiology over one decade. Infect. 2013;41(3):655–62.
[32] Sandven P, Bevanger L, Digranes A, Haukland HH, Mannsåker T, Gaustad P. Norwegian Yeast Study
Group. Candidemia in Norway (1991 to 2003): results from a nationwide study. J Clin Microbiol.
[33] Cisterna R, Ezpeleta G, Tellaria O, Guinea J, Regueiro B, Garcia-Rodriguez J, Esperalba J. Spanish
Candidemia Surveillance Group. Nationwide sentinel surveillance of bloodstream Candida infections
in 40 tertiary care hospital in Spain. J Clin Microbiol. 2010;48(11):4200–6.
[34] Pemán J, Cantón E, Quindós G. FUNGEMYCA Study Group. Epidemiology, species distribution and
in vitro antifungal susceptibility of fungaemia in a Spanish multicentre prospective survey. J
Antimicrob Chemother. 2012;67(5):1181–7.
[35] Pemán J, Cantón E, Linares-Sicilia MJ, Rosello E, Borrell N, Ruiz-Perez-de-Pipaon M, Guinea J,
Garcia J, Porras A, Garcia-Tapia A, Perez-del-Molino L, Suarez A, Alcoba J, Garcia-Garcia I.
Epidemiology and antifungal susceptibility of bloodstream fungal isolates in pediatric patients: a
Spanish multicenter prospective survey. J Clin Microbiol. 2011;49(12):4158–63.
[36] Ericsson J, Chryssanthou E, Klingspor L, Johnsson A, ljungman P, Svensson E, Sjolin J. Candiaemia
in Sweden: a nationwide prospective observational survey. Clin Microbiol Infect Dis. 2013;19(4): E218–21.
[37] Marchetti O, Bille J, Fluckiger U. Fungal Infection Network of Switzerland. Epidemiology of
candidemia in Swiss tertiary care hospitals: secular trends, 1991–2000. Clin Infect Dis. 2004;38(3): 311–20.
[38] Kibbler CC, Seaton S, Barnes RA, Gransden W, Holliman R, Johnson E, Perry J, Sullivan D, Wilson
J. Management and outcome of bloodstream infections due to Candida species in England and Wales.
J Hosp Infect. 2003;54(1):18–24.
[39] Chalmers C, Gaur S, Chew J, Wright T, Kumar A, Mathur S, Wan W, Gould I, Leanord A, Bal A.
Epidemiology and management of candidaemia- a retrospective multicentre study in five hospitals in
the UK. Mycoses. 2011;54(6):e795–800.
[40] Yapar N, Pullukcu H, Avkan-Oguz V, Sayin-Kutlu S, Ertugrul B, Sacar S, Cetin B, Kaya O. Evaluation
of species distribution and risk factors of candidemia: a multicenter case-control study. Med Mycol.
[41] Chen S, Slavin M, Nguyen Q. Australian Candidemia Study. Active surveillance for candidemia,
Australia. Emerg Infect Dis. 2006;12(10):1508–1516.
[42] Playford GE, Marriott D, Nguyen Q, Chen S, Ellis D, Slavin M, Sorrell T. Candidemia in
nonneutropenic critically ill patients: Risk factors for non-albicans Candida spp. Crit Care Med.
[43] Zhang XB, Yu SJ, Yu JX, Gong YL, Feng W, Sun FJ. Retrospective analysis of epidemiology and
prognostic factors for candidemia at a hospital in China, 2000–2009. Jpn J Infect Dis. 2012;65(6):510–5.
[44] Guo F, Yang Y, Kang Y, Zang B, Cui W, Qin Y, Fang Q, Qin T, Jiang D, Li W, Gu Q, Zhao H, Liu D,
Guan X, Li J, Ma X, Yu K, Chan D, Yan J, Tang Y, Liu W, Li R, Qiu H. m. Invasive candidiasis in
intensive care units in China: a multicentre prospective observational study. J Antimicrob Chemother.
[45] Tan TY, Tan AL, Tee NWS, Ng LSY, Chee CW. The increased role of non-albicans species in
candidaemia: Results from a 3-year surveillance study. Mycoses. 2010;53(6):515–21.
[46] Kreusch A, Karstaedt AS. . Candidemia among adults in Soweto, South Africa, 1990–2007.
Int J Infect Dis. 2013;17(8):e621–3.
[47] Mukaremera L, Lee KK, Mora-Montes HM, Gow NAR. Candida albicans yeast,
pseudohyphal, and hyphal morphogenesis differentially affects immune recognition.
Front Immunol. 2017 Jun 7;8(JUN):629.
[48] Deorukhkar SC. Virulence Traits Contributing to Pathogenicity of Candida Species. J Microbiol Exp.
2017 Jun 14;5(1). Available from:
[49] Garcia MC, Lee JT, Ramsook CB, Alsteens D, Dufrêne YF, Lipke PN. A role for amyloid in cell
aggregation and biofilm formation. PLoS One. 2011;6(3):e17632. Available from:
[50] Mayer FL, Wilson D, Hube B. Candida albicans pathogenicity mechanisms. Virulence. 2013 Feb
15;4(2):119. Available from: /pmc/articles/PMC3654610/.
[51] Nikoomanesh F, Roudbarmohammadi S, Roudbary M, Bayat M, Heidari G. Investigation of bcr1 Gene
Expression in Candida albicans Isolates by RT-PCR Technique and its Impact on Biofilm Formation.
Infect Epidemiol Med. 2016;2(1):22–4.
[52] Roudbarmohammadi S, Roudbary M, Bakhshi B, Katiraee F, Mohammadi R, Falahati M. ALS1 and
ALS3 gene expression and biofilm formation in Candida albicans isolated from vulvovaginal
candidiasis. Adv Biomed Res. 2016;5(1):105. Available from: /pmc/articles/PMC4918214/.
[53] Silva S, Negri M, Henriques M, Oliveira R, Williams DW, Azeredo J. Candida glabrata, Candida
parapsilosis and Candida tropicalis: Biology, epidemiology, pathogenicity and antifungal resistance.
Vol. 36, FEMS Microbiology Reviews. FEMS Microbiol Rev; 2012. p. 288–305. Available from:
[54] Rodríguez-Cerdeira C, Martínez-Herrera E, Carnero-Gregorio M, López-Barcenas A, Fabbrocini G,
Fida M,El-Samahy M, Gonzalea-Cespon J. Pathogenesis and Clinical Relevance of Candida Biofilms
in Vulvovaginal Candidiasis. Front Microbiol. 2020 Nov 11;11. Available from:
[55] Modrzewska B, Kurnatowski P. Adherence of Candida sp. to host tissues and cells as one of its
pathogenicity features – PubMed. Ann Parasitol. 2015. p. 3–9. Available from:
[56] Hostetter MK. Adhesins and ligands involved in the interaction of Candida spp. with epithelial and
endothelial surfaces. Vol. 7, Clinical Microbiology Reviews. 1994. p. 29–42. Available from:
[57] Finkel JS, Xu W, Huang D, Hill EM, Desai JH, Woolford CA, Nett J, Taff H, Norice C, Andes D,
Lanni F, Mitchell A. Portrait of Candida albicans adherence regulators.
PLoS Pathog. 2012;8:e1002525.
[58] Holland LM, Schröder MS, Turner SA, Taff H, Andes D, Grózer Z, Gacser A, Ames L, Haynes K,
Higgins D, Butler G. Comparative phenotypic analysis of the major fungal pathogens Candida
parapsilosis and Candida albicans. PLoS Pathog. 2014;10:e1004365.
[59] Mendelsohn, S, Pinsky M, Weissman Z, and Kornitzer D. Regulation of the Candida albicans hypha
inducing transcription factor Ume6 by the CDK1 cyclins Cln3 and Hgc1. mSphere. 2017;2:e00248-16.
[60] Freire, F, de Barros PP, Pereira CA, Junqueira JC, and Jorge A. Photodynamic inactivation in the
expression of the Candida albicans genes ALS3, HWP1, BCR1, TEC1, CPH1, and EFG1 in biofilms.
Lasers Med Sci. 2018;33:1447–1454.
[61] Su, C, Yu J, and Lu Y. Hyphal development in Candida albicans from different cell states.
Curr Genet. 2018;64:1239–1243.
[62] Guan, G, Xi J, Tao L, Nobile CJ, Sun Y, Cao C,Tong Y, Huang G. Bcr1 plays a central role in the
regulation of opaque cell filamentation in Candida albicans. Mol Microbiol. 2013;89:732–750.
[63] Inglis, DO, and Sherlock G. Ras signaling gets fine-tuned: regulation of multiple pathogenic traits of
Candida albicans. Eukaryot Cell. 2013;12:1316–1325.
[64] Orsi C, Borghi E, Colombari B, Neglia RG, Quaglino D, Ardizzoni A, Morace G, Blasi E. Impact of
Candida albicans hyphal wall protein 1 (HWP1) genotype on biofilm production and fungal
susceptibility to microglial cells. Microb Pathog. 2014;6:20–7.
[65] Marak, MB, and Dhanashree B. Antifungal susceptibility and biofilm production of Candida spp.
isolated from clinical samples. Int J Microbiol. 2018;2018:7495218.
[66] Burgain, A, Pic E, Markey L, Tebbji F, Kumamoto CA, and Sellam A. A novel genetic circuitry
governing hypoxic metabolic flexibility, commensalism and virulence in the fungal pathogen Candida
albicans. PLoS Pathog. 2019;15:e1007823.
[67] Valotteau C, Prystopiuk V, Cormack BP, Dufrêne YF, and Mitchell AP. Atomic force microscopy
demonstrates that Candida glabrata uses three Epa proteins to mediate
adhesion to abiotic surfaces. mSphere. 2019;4:e00277-19.
[68] Gulati, M, and Nobile CJ. Candida albicans biofilms: development, regulation,
and molecular mechanisms. Microbes Infect. 2016;18:310–21.
[69] Mitchell KF, Zarnowski R, Sanchez H, Edward JA, EL R, NettJ E. Community participation in biofilm
matrix assembly and function. Proc Natl Acad Sci USA. 2015;112:4092–4097.
[70] Dominguez E, Zarnowski R, Sanchez H, Covelli AS, Westler WM, Azadi P, Nett j, Mitchell A, Andes
D. Conservation and divergence in the Candida species biofilm matrix mannan-glucan complex
structure, function, and genetic control. MBio. 2018;9:e00451-18.
[71] Vandeputte P, Pradervand S, Ischer F, Coste AT, Ferrari S, Harshman K, Sanglard D. Identification
and functional characterization of Rca1, a transcription factor involved in both antifungal susceptibility
and host response in Candida albicans. Eukaryot Cell. 2012;11:916–931.
[72] van Wijlick L, Swidergall M, Brandt P, and Ernst JF. Candida albicans responds to glycostructure
damage by Ace2-mediated feedback regulation of Cek1 signaling. Mol Microbiol. 2016;102:827–849.
[73] Ganguly S, Bishop AC, Xu W, Ghosh S, Nickerson KW, Lanni F,Patton-Vogt, Mitchell A. Zap1
control of cell-cell signaling in Candida albicans biofilms. Eukaryot Cell. 2011;10:1448–1454.
[74] Deorukhkar SC, Saini S. Why Candida Species have Emerged as Important Nosocomial Pathogens?
Int J Curr Microbiol Appl Sci. 2016 Jan 10;5(1):533–45.
[75] Deorukhkar SC, Saini S. Medical Device-Associated Candida Infections in a Rural Tertiary Care
Teaching Hospital of India. Interdiscip Perspect Infect Dis. 2016;2016.
[76] Cavalheiro M, Teixeira MC. Candida Biofilms: Threats, Challenges, and Promising Strategies. Front
Med. 2018; 5(FEB). Available from:
[77] Tseng YK, Chen YC, Hou CJ, Deng FS, Liang SH, Hoo SY, Hsu C, Ke C, Lin C. Evaluation of Biofilm
Formation in Candida tropicalis Using a Silicone-Based Platform with Synthetic Urine Medium.
Microorganisms. 2020;8(5). Available from:
[78] Fanning S, Mitchell AP. Fungal biofilms. PLoS Pathog. 2012;8(4):149–57. Available from:
[79] Uppuluri, P, Chaturvedi, AK, Srinivasan, A, Banerjee, M, Ramasubramaniam, AK, Köhler, JR,
Kadosh, D, & Lopez-Ribot, JL. Dispersion as an important step in the Candida albicans biofilm
developmental cycle. PLoS Pathog. 2010 Mar;6(3). Available from:
[80] Sardi JCO, Scorzoni L, Bernardi T, Fusco-Almeida AM, Mendes Giannini MJS. Candida species:
Current epidemiology, pathogenicity, biofilm formation, natural antifungal products and new
therapeutic options. Vol. 62, Journal of Medical Microbiology. 2013. p. 10–24. Available from:
[81] de Cássia Orlandi Sardi J, Silva DR, Soares Mendes-Giannini MJ, Rosalen PL. Candida auris:
Epidemiology, risk factors, virulence, resistance, and therapeutic options. Vol. 125, Microbial
Pathogenesis. 2018. p. 116–21. Available from:
[82] Sachin C, Ruchi K, Santosh S. In vitro evaluation of proteinase, phospholipase and haemolysin
activities of Candida species isolated from clinical specimens. Int J Med Biomed Res. 2012;1(2):153–7.
[83] Ghannoum MA. Potential Role of Phospholipases in Virulence and Fungal Pathogenesis. Clin
Microbiol Rev. 2000;13(1):122–43. Available from:
[84] Dalle F, Wächtler B, L’Ollivier C, Holland G, Bannert N, Wilson D, Labruere C, Bonnin A, Hube B.
Cellular interactions of Candida albicans with human oral epithelial cells and enterocytes. Cell
Microbiol. 2010;12(2):248–71. Available from:
[85] Zoppo M, Poma N, Di Luca M, Bottai D, Tavanti A. Genetic manipulation as a tool to unravel Candida
parapsilosis species complex virulence and drug resistance: state of the art. Journal of Fungi.
Multidisciplinary Digital Publishing Institute; 2021. p. 459. Available from:
[86] Luo G, Samaranayake LP, Cheung BPK, Tang G. Reverse transcriptase polymerase chain reaction
(RT-PCR) detection of HLP gene expression in Candida glabrata and its possible role in in vitro
haemolysin production. APMIS. 2004;112(4–5):283–90. Available from:
[87] Rodrigues AG, Pina-Vaz C, Costa-De-Oliveira S, Tavares C. Expression of Plasma Coagulase among
Pathogenic Candida Species. J Clin Microbiol. 2003;41(12):5792–3. Available from:
[88] Yigit N, Aktas E, Dagistan S, Ayyildiz A. Investigating Biofilm Production, Coagulase and Hemolytic
Activity in Candida Species Isolated From Denture Stomatitis Patients. Eurasian J Med. 2011;43(1):
27–32. Available from:
[89] Gácser A, Stehr F, Kröger C, Kredics L, Schäfer W, Nosanchuk JD. Lipase 8 affects the pathogenesis
of Candida albicans. Infect Immun. 2007 Oct; 75(10):4710–8. Available from:
[90] Kurzai O, Schmitt C, Bröcker EB, Frosch M, Kolb-Mäurer A. Polymorphism of Candida albicans is a
major factor in the interaction with human dendritic cells. Int J Med Microbiol. 2005;295(2):121–7.
Available from:
[91] Min K, Naseem S, Konopka JB. N-Acetylglucosamine Regulates Morphogenesis and Virulence
Pathways in Fungi. J fungi (Basel, Switzerland). 2019;6(1). Available from:
[92] Henriques M, Silva S. Candida albicans virulence factors and its pathogenicity.
Microorganisms. 2021;9(4):11–3.
[93] Zhang LJ, Yu SB, Li WG, Zhang WZ, Wu Y, Lu JX. Polymorphism analysis of virulence-related genes
among Candida tropicalis isolates. Chin Med J (Engl). 2019;132(4):446–53. Available from:
[94] Soll DR. Why does Candida albicans switch?, FEMS Yeast Research. 2009. p. 973–89. Available
[95] Alby K, Bennett RJ. Stress-induced phenotypic switching in Candida albicans. Mol Biol Cell. 2009
Jul 15;20(14):3178–91. Available from: /pmc/articles/PMC2710840/.
[96] Mane A, Gaikwad S, Bembalkar S, Risbud A. Increased expression of virulence attributes in oral
Candida albicans isolates from human immunodeficiency virus-positive individuals. J Med Microbiol.
2012;61(Pt 2):285–90. Available from:
[97] Csank C, Haynes K. Candida glabrata displays pseudohyphal growth. FEMS Microbiol Lett.
2000;189(1):115–20. Available from:
[98] Ksiezopolska E, Gabaldón T. Evolutionary emergence of drug resistance in candida opportunistic
pathogens [Internet]. Vol. 9, Genes. Multidisciplinary Digital Publishing Institute (MDPI);
2018 [cited 2022 Jan 17]. Available from: /pmc/articles/PMC6162425/.
[99] Bhattacharya S, Sae-Tia S, Fries BC. Candidiasis and mechanisms of antifungal resistance.
Antibiotics. Multidisciplinary Digital Publishing Institute (MDPI); 2020. p. 1–19.
Available from: /pmc/articles/ PMC7345657/.
[100] Pappas PG, Lionakis MS, Arendrup MC, Ostrosky-Zeichner L, Kullberg BJ. Invasive candidiasis. Nat
Rev Dis Prim. 2018;4. Available from:
[101] Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA, Ostrosky-Zeichner L,Reboli A, Schuster
M, Vazquez J, Walsh T, Zaoutis T, Sobel J. Clinical Practice Guideline for the Management of
Candidiasis: 2016 Update by the Infectious Diseases Society of America. Vol. 62, Clinical Infectious
Diseases. 2015. p. e1–50. Available from:
[102] Arendrup MC, Perlin DS. Echinocandin resistance: An emerging clinical problem? Current Opinion
in Infectious Diseases. 2014. p. 484–92. Available from:
[103] Berkow EL, Lockhart SR. Fluconazole resistance in Candida species: A current perspective. Vol. 10,
Infection and Drug Resistance. 2017. p. 237–45. Available from:
[104] Sanguinetti M, Posteraro B, Lass‐Flörl C. Antifungal drug resistance among Candida species:
mechanisms and clinical impact. Mycoses. 2015;58:2–13.
[105] Zuo T, Zhan H, Zhang F, Liu Q, Tso EYK, Lui GCY, Chen N, Li A, Lu W, Chan F, Chan PKS, Siew
NG. Alterations in Fecal Fungal Microbiome of Patients With COVID-19 During Time of
Hospitalization until Discharge. Gastroenterology. 2020;159(4):1302-1310.e5. Available from:
[106] Garcia-Effron G, Katiyar SK, Park S, Edlind TD, Perlin DS. A naturally occurring proline-to-alanine
amino acid change in Fks1p in Candida parapsilosis, Candida orthopsilosis, and Candida metapsilosis
accounts for reduced echinocandin susceptibility. Antimicrob Agents Chemother. 2008;52(7):2305–12.
Available from:
[107] Vallabhaneni S, Kallen A, Tsay S, Chow N, Welsh R, Kerins J, Kemble, S. K. Pacilli, M. Black, S. R.
Landon, E. Ridgway, J. Palmore, T. N. Zelzany, A. Adams, E. H. Quinn, M. Chaturvedi, S.
Investigation of the First Seven Reported Cases of Candida auris, a Globally Emerging Invasive,
Multidrug-Resistant Fungus—United States, May 2013–August 2016. American Journal of
Transplantation. 2017. p. 296–9. Available from:
[108] Chowdhary A, Voss A, Meis JF. Multidrug-resistant Candida auris: ‘new kid on the block’ in
hospital associated infections?. Journal of Hospital Infection. 2016. p. 209–12. Available from:
[109] Pfaller MA, Rhomberg PR, Messer SA, Jones RN, Castanheira M. Isavuconazole, micafungin, and 8
comparator antifungal agents’ susceptibility profiles for common and uncommon opportunistic fungi
collected in 2013: Temporal analysis of antifungal drug resistance using CLSI species-specific clinical
breakpoints and prop. Diagn Microbiol Infect Dis. 2015;82(4):303–13. Available from:
[110] Kodedová M, Sychrová H. Changes in the sterol composition of the plasma membrane affect
membrane potential, salt tolerance and the activity of multidrug resistance pumps in Saccharomyces
cerevisiae. PLoS One. 2015;10(9). Available from:
[111] Bhattacharya S, Esquivel BD, White TC. Overexpression or Deletion of Ergosterol Biosynthesis Genes
Alters Doubling Time, Response to Stress Agents, and Drug Susceptibility in Saccharomyces
cerevisiae. MBio. 2018;9(4). Available from:
[112] Jenks JD, Salzer HJF, Prattes J, Krause R, Buchheidt D, Hoenigl M. Spotlight on isavuconazole in the
treatment of invasive aspergillosis and mucormycosis: design, development, and place in therapy. Drug
Des Devel Ther [Internet]. 2018 Apr 30 [cited 2022 Jan 17];12:1033–44. Available from:
[113] Yasu T, Konuma T, Kuroda S, Takahashi S, Tojo A. Effect of cumulative intravenous voriconazole
dose on renal function in hematological patients. Antimicrob Agents Chemother [Internet]. 2018 Sep 1
[cited 2022 Jan 17];62(9). Available from:
[114] Wilson DT, Dimondi VP, Johnson SW, Jones TM, Drew RH. Role of isavuconazole in the treatment
of invasive fungal infections. Therapeutics and Clinical Risk Management. 2016. p. 1197–206.
Available from:
[115] Feng W, Yang J, Xi Z, Qiao Z, Lv Y, Wang Y, Yan M, Yanqing W, Wen C. Mutations and/or
Overexpressions of ERG4 and ERG11 Genes in Clinical Azoles-Resistant Isolates of Candida
albicans. Microb Drug Resist. 2017;23(5):563–70. Available from:
[116] Efimova SS, Schagina L V., Ostroumova OS. Investigation of channel-forming activity of polyene
macrolide antibiotics in planar lipid bilayers in the presence of dipole modifiers. Acta Naturae.
2014;6(23):67–79. Available from:
[117] Van Daele R, Spriet I, Wauters J, Maertens J, Mercier T, Van Hecke S, Bruggemann R. Antifungal
drugs: What brings the future? In: Medical Mycology. Oxford Academic; 2019. p. S328–43. Available
[118] Perlin DS. Current perspectives on echinocandin class drugs. Future Microbiology. 2011. p. 441–57.
Available from:
[119] Vermes A, Guchelaar HJ, Dankert J. Flucytosine: A review of its pharmacology, clinical indications,
pharmacokinetics, toxicity and drug interactions. J Antimicrob Chemother. 2000;46(2):171–9.
Available from:
[120] Xu Y, Chen L, Li C. Susceptibility of clinical isolates of Candida species to fluconazole and detection
of Candida albicans ERG11 mutations. J Antimicrob Chemother [Internet]. 2008;61(4):798–804.
Available from:
[121] Cleveland AA, Farley MM, Harrison LH, Stein B, Hollick R, Lockhart SR, Magill SS, Derado G, Park
BJ, Chiller TM. Changes in incidence and antifungal drug resistance in candidemia: results from
population-based laboratory surveillance in Atlanta and Baltimore, 2008-2011. Clin Infect Dis. 2012
Nov;55(10):1352–61. Available from:
[122] Lockhart SR, Etienne KA, Vallabhaneni S, Farooqi J, Chowdhary A, Govender NP, Arnaldo LC,
Belinda C, Christina AC, Cuomo CA, Desjardins CA, Berkow EL, Castanherira M, Magobo RE,
Jabeen K, Asghar RJ, Meis JF, Jackson B, Chiller T, Litvintseva AP. Simultaneous emergence of
multidrug-resistant Candida auris on 3 continents confirmed by whole-genome sequencing and
epidemiological analyses. Clin Infect Dis. 2017;64(2):134–40. Available from:
[123] Schneider S, Morschhäuser J. Induction of Candida albicans drug resistance genes by hybrid zinc
cluster transcription factors. Antimicrob Agents Chemother. 2015;59(1):558–69.
[124] Spencer W Redding, William R Kirkpatrick, Stephen Saville, Brent J Coco, William White, Annette
Fothergill, Michael Rinaldi, Tony Eng, Thomas F Patterson and Jose Lopez-Ribot. Multiple patterns
of resistance to fluconazole in Candida glabrata isolates from a patient with oropharyngeal candidiasis
receiving head and neck radiation. J Clin Microbiol. 2003;41(2):619–22. Available from:
[125] Ribeiro MA, Paula CR. Up-regulation of ERG11 gene among fluconazole-resistant Candida albicans
generated in vitro: is there any clinical implication? Diagn Microbiol Infect Dis. 2007; 57(1):71–5.
Available from:
[126] Tavakoli M, Zaini F, Kordbacheh M, Safara M, Raoofian R, Heidari M. Upregulation of the ERG11
gene in Candida krusei by azoles. DARU, J Pharm Sci. 2010;18(4):276–80. Available from:
[127] Rogers PD, Barker KS. Evaluation of differential gene expression in fluconazole-susceptible and –
resistant isolates of Candida albicans by cDNA microarray analysis.
Antimicrob Agents Chemother. 2002;46(11):3412–7.
[128] Prasad R, Rawal MK, Shah AH. Candida efflux ATPases and antiporters in clinical drug resistance.
In: Advances in Experimental Medicine and Biology. Springer, Cham; 2016. p. 351–76. Available
[129] Whaley SG, Berkow EL, Rybak JM, Nishimoto AT, Barker KS, Rogers PD. Azole antifungal
resistance in Candida albicans and emerging non-albicans Candida Species. Frontiers in
Microbiology. 2017. p. 2173. Available from:
[130] Perea S, López-Ribot JL, Kirkpatrick WR, McAtee RK, Santillán RA, Martı́nez M, Calabrese D,
Sanglard D, Patterson T. Prevalence of molecular mechanisms of resistance to azole antifungal agents
in Candida albicans strains displaying high-level fluconazole resistance isolated from human
immunodeficiency virus-infected patients. Antimicrob Agents Chemother. 2001;45(10):2676–84.
[131] Sasse C, Schillig R, Dierolf F, Weyler M, Schneider S, Mogavero S, Rogers PD, Morschhauser J. The
transcription factor Ndt80 does not contribute to Mrr1-, Tac1-, and Upc2-mediated fluconazole
resistance in Candida albicans. PLoS One. 2011;6(9).
[132] Zare-Bidaki M, Maleki A, Ghanbarzadeh N, Nikoomanesh F. Expression pattern of drug-resistance
genes ERG11 and TAC1 in Candida albicans Clinical isolates. Mol Biol Rep. 2022 Sep 28. DOI:
[133] Zhang H, Xu Q, Li S, Ying Y, Zhang Z, Zeng L, Huamg XT, Huang SH. Gene expression analysis of
key players associated with fluconazole resistance in Candida albicans. Jundishapur J Microbiol.
[134] Lee Y, Puumala E, Robbins N, Cowen LE. Antifungal Drug Resistance: Molecular Mechanisms in
Candida albicans and beyond. Chemical Reviews. American Chemical Society; 2021. p. 3390–411.
Available from:
[135] Cowen LE, Sanglard D, Howard SJ, Rogers PD, Perlin DS. Mechanisms of antifungal drug resistance.
Cold Spring Harb Perspect Med. 2015;5(7). Available from: /pmc/articles/PMC4484955/.
[136] Chaabane F, Graf A, Jequier L, Coste AT. Review on Antifungal Resistance Mechanisms in the
Emerging Pathogen Candida auris. Front Microbiol. 2019 Nov 29; 10:2788. Available from:
[137] Bennett JE, Izumikawa K, Marr KA. Mechanism of Increased Fluconazole Resistance in Candida
glabrata during Prophylaxis. Antimicrob Agents Chemother. 2004;48(5):1773–7.
[138] Spettel K, Barousch W, Makristathis A, Zeller I, Nehr M, Selitsch B, Lackner M, Rath PM, steinmann
J. Analysis of antifungal resistance genes in Candida albicans and Candida glabrata using next
generation sequencing. PLoS One. 2019;14(1):1–19.
[139] Tomitori H, Kashiwagi K, Sakata K, Kakinuma Y, Igarashi K. Identification of a gene for a polyamine
transport protein in yeast. J Biol Chem. 1999;274(6):3265–7. Available from:
[140] Ferrari S, Ischer F, Calabrese D, Posteraro B, Sanguinetti M, Fadda G, Rohde B, Bause C, Bader O,
Sanglard D. Gain of function mutations in CgPDR1 of Candida glabrata not only mediate antifungal
resistance but also enhance virulence. PLoS Pathog. 2009 J;5(1). Available from:
[141] Arendrup MC, Rodriguez-Tudela JL, Park S, Garcia-Effron G, Delmas G, Cuenca-Estrella M, Lopez
AG, Perlin DS. Echinocandin susceptibility testing of Candida spp. using EUCAST EDef 7.1 and CLSI
M27-A3 standard procedures: Analysis of the influence of bovine serum albumin supplementation,
storage time, and drug lots. Antimicrob Agents Chemother. 2011;55(4):1580–7. Available from:
[142] Denning DW, Bromley MJ. How to bolster the antifungal pipeline: Few drugs are coming to market,
but opportunities for drug development exist. Science. 2015. p. 1414–6. Available from:
[143] Chang YL, Yu SJ, Heitman J, Wellington M, Chen YL. New facets of antifungal therapy, Virulence.
2017. p. 222–36. Available from:
[144] Perfect JR. The antifungal pipeline: A reality check, Nature Reviews Drug Discovery. Nature
Publishing Group; 2017. p. 603–16. Available from:
[145] Rauseo AM, Coler-Reilly A, Larson L, Spec A. Hope on the horizon: Novel fungal treatments in
development. Vol. 7, Open Forum Infectious Diseases. 2020. Available from:
[146] Nikoomanesh F, Roudbarmohammadi S, Khoobi M, Haghighi F, Roudbary M. Design and synthesis
of mucoadhesive nanogel containing farnesol: investigation of the effect on HWP1, SAP6 and Rim101
genes expression of Candida albicans in vitro. Artif Cells, Nanomedicine Biotechnol. 2019;47(1):64–72.
[147] Tiwari BK, Valdramidis VP, O’Donnell CP, Muthukumarappan K, Bourke P, Cullen PJ. Application
of natural antimicrobials for food preservation. Journal of Agricultural and Food Chemistry. 2009. p.
5987–6000. Available from:
[148] Mathur M, Devi VK. Potential of novel drug delivery systems in the management of topical candidiasis.
Journal of Drug Targeting. 2017. p. 685–703. Available from:
[149] Kogan A, Garti N. Microemulsions as transdermal drug delivery vehicles. Adv Colloid Interface Sci.
2006;123–126(SPEC. ISS.):369–85. Available from:
[150] Chudasama A, Patel V, Nivsarkar M, Vasu K, Shishoo C. Investigation of microemulsion system for
transdermal delivery of itraconazole. J Adv Pharm Technol Res. 2011;2(1):30–8.
Available from: /pmc/articles/PMC3217682/.
[151] Torchilin VP. Micellar nanocarriers: Pharmaceutical perspectives. Pharmaceutical Research. 2007. p.
1–16. Available from:
[152] Bachhav YG, Mondon K, Kalia YN, Gurny R, Möller M. Novel micelle formulations to increase
cutaneous bioavailability of azole antifungals. J Control Release. 2011;153(2):126–32. Available from:
[153] Güngör S, Erdal MS, Aksu B. New Formulation Strategies in Topical Antifungal Therapy. J Cosmet
Dermatological Sci Appl. 2013;03(01):56–65. Available from:
[154] Garg A, Sharma GS, Goyal AK, Ghosh G, Si SC, Rath G. Recent advances in topical carriers of
anti fungal agents. Heliyon. 2020 Aug 1;6(8):e04663.
[155] Sinico C, Fadda AM. Vesicular carriers for dermal drug delivery. Expert Opinion on Drug Delivery.
2009. p. 813–25. Available from:
[156] Pierre MBR, Dos Santos Miranda Costa I. Liposomal systems as drug delivery vehicles for dermal and
transdermal applications. Archives of Dermatological Research. Springer; 2011. p. 607–21. Available
[157] Voltan AR, Quindós G, Alarcón KPM, Fusco-Almeida AM, Mendes-Giannini MJS, Chorilli M. Fungal
diseases: Could nanostructured drug delivery systems be a novel paradigm for therapy?. International
Journal of Nanomedicine. 2016. p. 3715–30. Available from:
[158] Hanson LH, Stevens DA. Comparison of antifungal activity of amphotericin B deoxycholate
suspension with that of amphotericin B cholesteryl sulfate colloidal dispersion.
Antimicrob Agents Chemother. 1992;36(2):486–8.
[159] Polacheck I, Nagler A, Okon E, Drakos P, Plaskowitz J, Kwon-Chung KJ. Aspergillus quadrilineatus,
a new causative agent of fungal sinusitis. J Clin Microbiol. 1998;30(2):3290–3.
[160] Hostetler JS, Clemons K V, Hanson LH, Stevens DA. Efficacy and safety of amphotericin B colloidal
dispersion compared with those of amphotericin B deoxycholate suspension for treatment of
disseminated murine cryptococcosis. Antimicrob Agents Chemother. 1992;36(12):2656–60.
[161] Tkatch LS, Kusne S, Eibling D. Successful treatment of zygomycosis of the paranasal sinuses with
surgical debridement and amphotericin B colloidal dispersion. Am J Otolaryngol. 1993;14(4):249–53.
[162] Vukmir RB, Kusne S, Linden P, Pasculle W, Fothergill AW, Sheaffer J, Nieto J, Segal R, Merhav H,
Martinez AJ. Successful therapy for cerebral phaeohyphomycosis due to Dactylaria gallopava in a liver
transplant recipient. Clin Infect Dis. 1994;19(4):714–9.
[163] Herbrecht R, V L-B, Bowden RA, Kusne S, Anaissie EJ, Graybill JR, Noskin GA, Oppenheim, Andres
E, Pietrelli LA. Treatment of 21 cases of invasive mucormycosis with amphotericin B colloidal
dispersion. Eur J Clin Microbiol Infect Dis. 2001;20(7):460–6.
[164] Arney KL, Tiernan R, Judson MA. Primary pulmonary involvement of Fusarium solani in a lung
transplant recipient. Chest. 1997;112(4):1128–30.
[165] Hunstad DA, Cohen AH, St Geme JW. Successful eradication of mucormycosis occurring in a
pulmonary allograft. J Hear Lung Transpl. 1999;18(8):801–4.
[166] Quindós G, Carrillo-Muñoz AJ, Arévalo MP. In vitro susceptibility of Candida dubliniensis to current
and new antifungal agent. Chemotherapy. 2000;46(6):395–401.
[167] Weiler S, Uberlacher E, Schofmann J, Stienecke E, Dunzendorefer S, Joannidis M, Bellmann R.
Pharmacokinetics of amphotericin B colloidal dispersion in critically ill patients with cholestatic liver
disease. Antimicrob Agents Chemother. 2012;56(10):5414–8.
[168] Capilla J, Clemons K V, Sobel RA. Efficacy of ampho_tericin B lipid complex in a rabbit model of
coccidioidal mening. J Antimicrob Chemother. 2007;60(3):673–6.
[169] Severino P, Andreani T, Macedo AS, Fangueiro JF, Santana MHA, Silva AM, souto EB. Current
State of-Art and New Trends on Lipid Nanoparticles (SLN and NLC) for Oral Drug Delivery. J Drug Deliv.
2012;2012:1–10. Available from:
[170] Mudshinge SR, Deore AB, Patil S, Bhalgat CM. Nanoparticles: Emerging carriers for drug delivery.
Saudi Pharmaceutical Journal. Elsevier; 2011. p. 129–41. Available from: /pmc/articles/PMC 3744999/.
[171] Subramanian S, Singireddy A, Krishnamoorthy K, Rajappan M. Nanosponges: A novel class of drug
delivery system – Review. J Pharm Pharm Sci. 2012; 15(1):103–11. Available from:
[172] Sousa F, Ferreira D, Reis S, Costa P. Current insights on antifungal therapy: Novel nanotechnology
approaches for drug delivery systems and new drugs from natural sources. Pharmaceuticals.
Multidisciplinary Digital Publishing Institute (MDPI); 2020 p. 1–30. Available from:
[173] Gajbhiye S, Sakharwade S. Silver Nanoparticles in Cosmetics. J Cosmet Dermatological Sci Appl.
2016;06(01):48–53. Available from:
[174] Keuk-JunK K, Sung SW, Moon S, Choi J, KimJG, Lee DG. Antifungal Effect of Silver Nanoparticles
on Dermatophytes. J Microbiol Biotechnol. 2018;18(8):1482–4.
[175] Ashour SM. Silver nanoparticles as antimicrobial agent from Kluyveromyces marxianus and Candida
utilis. Int J Curr Microbiol Appl Sci. 2014;3(8):384–96.
[176] Lara HH, Romero-Urbina DG, Pierce C, Lopez-Ribot JL, Arellano-Jiménez MJ, Jose-Yacaman M.
Effect of silver nanoparticles on Candida albicans biofilms: An ultrastructural study. J
Nanobiotechnology. 2015;13(1):1–12. Available from:
[177] Hu X, Zhang Y, Ding T, Liu J, Zhao H. Multifunctional Gold Nanoparticles: A Novel Nanomaterial
for Various Medical Applications and Biological Activities. Frontiers in Bioengineering and
Biotechnology. Frontiers Media S.A.; 2020. p. 990.
[178] Rahimi H, Roudbarmohammadi S, Hamid Delavari H, Roudbary M. Antifungal effects of indolicidin conjugated gold nanoparticles against fluconazole-resistant strains of Candida albicans isolated from
patients with burn infection. Int J Nanomedicine. 2019;14:5323–38. Available from:
[179] Khatoon UT, Rao GVSN, Mohan MK, Ramanaviciene A, Ramanavicius A. Comparative study of
antifungal activity of silver and gold nanoparticles synthesized by facile chemical approach.
J Environ Chem Eng. 2018 Oct 1;6(5):5837–44.
[180] Sherwani A, Tufail S, Khan AA, Oais M. Gold Nanoparticle- Photosensitizer Conjugate Based
Photodynamic Inactivation of Biofilm Producing Cells: Potential for Treatment of C. albicansinfection
in BALB/c Mice. Int J Nanomedicine. 2015;10(7):e0131684.
[181] Mirzaeei S, Mohammadi G, Fattahi N, Mohammadi P, Fattahi A, Nikbakht MR, Adibkia K.
Formulation and physicochemical characterization of cyclosporine microfiber by electrospinning.
Adv Pharm Bull. 2019;9(2):249–54. Available from: /pmc/articles/PMC6664123/.
[182] Canbolat MF, Gera N, Tang C, Monian B, Rao BM, Pourdeyhimi B,Khan SA. Preservation of Cell
Viability and Protein Conformation on Immobilization within Nanofibers via Electrospinning
Functionalized Yeast. ACS Appl Mater Interfaces. 2013;5(19):9349–54.
[183] Dong G, Xiao X, Liu X, Qian B, Ma Z, Ye S,Chen D, Qiu J. Preparation and characterization of Ag
nanoparticle-embedded polymer electrospun nanofibers. J Nanoparticle Res. 2010;12(4):1319–29.
[184] Vashisth P, Kumar N, Pemmaraju SC, Pruthi PA, Mallick V, Singh H, Mishra NC, Singh RP, Pruthi
V, Patel A. Antibiofilm activity of quercetin-encapsulated cytocompatible nanofibers against Candida
albicans. J Bioact Compat Polym. 2013;28(6):652–65.
[185] Rastian Z, Khodadadi AA, Guo Z, Vahabzadeh F, Mortazavi Y. Plasma Functionalized Multiwalled
Carbon Nanotubes for Immobilization of Candida antarctica Lipase B: Production of Biodiesel from
Methanolysis of Rapeseed Oil. Appl Biochem Biotechnol. 2016;178(5):974–89. Available from:
[186] Tonglairoum P, Ngawhirunpat T, Rojanarata T, Kaomongkolgit R, Opanasopit P. Fabrication of a
novel scaffold of clotrimazole microemulsion-containing nanofibers using an electrospinning process
for oral candidiasis applications, Colloids and Surfaces B: Biointerfaces.
[187] Sharma R, Garg T, Goyal AK, Rath G. Development, optimization and evaluation of polymeric
electrospun nanofibers: A tool for local delivery of fluconazole for management of vaginal candidiasis.
Artif Cells, Nanomedicine, Biotechnol. 2014.
[188] Venkataraman A, Amadi EV, Chen Y, Papadopoulos C. Carbon Nanotube Assembly and Integration
for Applications. Nanoscale Research Letters. SpringerOpen; 2019. p. 1–47. Available from:
[189] Saeedi T, Alotaibi HF, Prokopovich P. Polymer colloids as drug delivery systems for the treatment of
arthritis. Vol. 285, Advances in Colloid and Interface Science. Elsevier; 2020. p. 102273.
[190] Pridgen EM, Alexis F, Farokhzad OC. Polymeric Nanoparticle Technologies for Oral Drug Delivery.
Clin Gastroenterol Hepatol. 2014;12(10):1605–10. Available from: /pmc/articles/PMC4171204/.
[191] Voltan AR, Quindós G, Alarcón KPM, Fusco-Almeida AM, Mendes-Giannini MJS, Chorilli M. Fungal
diseases: Could nanostructured drug delivery systems be a novel paradigm for therapy?. International
Journal of Nanomedicine. 2016. p. 3715–30. Available from:
[192] Lengert E V., Talnikova EE, Tuchin V V., Svenskaya YI. Prospective Nanotechnology-Based
Strategies for Enhanced Intra- And Transdermal Delivery of Antifungal Drugs. Skin Pharmacology
and Physiology. Karger Publishers; 2020. p. 261–9. Available from:
[193] Krishnan BR, James KD, Polowy K, Bryant BJ, Vaidya A, Smith S, Laudeman CP. CD101, a novel
echinocandin with exceptional stability properties and enhanced aqueous solubility. J Antibiot (Tokyo).
2017;70(2):130–5. Available from:
[194] Ong V, Hough G, Schlosser M, Bartizal K, Balkovec JM, James KD, Krishnan BR. Preclinical
evaluation of the stability, safety, and efficacy of CD101, a novel echinocandin. Antimicrob Agents
Chemother. 2016;60(11):6872–9. Available from:
[195] Pfaller MA, Messer SA, Rhomberg PR, Jones RN, Castanheira M. Activity of a long-acting
echinocandin, CD101, determined using CLSI and EUCAST reference methods, against Candida and
Aspergillus spp., including echinocandin- and azole-resistant isolates. J Antimicrob Chemother.
2016;71(10):2868–73. Available from:
[196] Sandison T, Ong V, Lee J, Thye D. Safety and pharmacokinetics of CD101 IV, a novel echinocandin,
in healthy adults. Antimicrob Agents Chemother. 2017;61:e01627-16.
[197] Cidara Therapeutics. 2018. Cidara Therapeutics Reports Positive Topline Results from Phase 2
STRIVE Trial of Lead Antifungal Rezafungin. News Release. [Internet]. Available from:
[198] Schell WA, Jones AM, Borroto-Esoda K, Alexander BD. Antifungal activity of SCY-078 and standard
antifungal agents against 178 clinical isolates of resistant and susceptible Candida species. Antimicrob
Agents Chemother. 2017;61(11). Available from: /pmc/articles/PMC5655100/.
[199] Wring SA, Randolph R, Park SH, Abruzzo G, Chen Q, Flattery A, Garrett, Peel M, Outcalt R, Poweel
K, Truchsis M, Angulo D, Borroto-Esoda K. Preclinical pharmacokinetics and pharmacodynamic
target of SCY-078, a first-in-class orally active antifungal glucan synthesis inhibitor, in murine models
of disseminated candidiasis. Antimicrob Agents Chemother. 2017;61(4). Available from:
[200] Wring S, Murphy G, Atiee G, Corr C, Hyman M, Willett M, Angulo D. Clinical Pharmacokinetics and
Drug-Drug Interaction Potential for Coadministered SCY-078, an Oral Fungicidal Glucan Synthase
Inhibitor, and Tacrolimus. Clin Pharmacol Drug Dev. 2019;8(1):60–9. Available from:
[201] Weaver LK, Minichino D, Biswas C, Chu N, Lee JJ, Bittinger K, Albeituni S, Nichols KE, Behrens
EM. Microbiota-dependent signals are required to sustain TLR-mediated immune responses. JCI
Insight. 2019 Jan 10;4(1):e124370. DOI: 10.1172/jci.insight.124370.
[202] Larkin EL, Long L, Isham N, Borroto-Esoda K, Barat S, Angulo D, Wring S, Ghannoum M. A novel
1,3-beta-D-glucan inhibitor, IbrexafungeRP (formerly SCY-078), shows potent activity in the lower
pH environment of vulvovaginitis. Antimicrob Agents Chemother. 2019;63(5).
Available from: /pmc/articles/PMC6496072/.
[203] Wiederhold NP, Najvar LK, Jaramillo R, Olivo M, Pizzini J, Catano G, Patterson TF. Oral glucan
synthase inhibitor SCY-078 is effective in an experimental murine model of invasive candidiasis
caused by WT and echinocandin-resistant Candida glabrata. J Antimicrob Chemother.
2018;73(2):448. Available from: /pmc/articles/PMC5890676/.
[204] Spec A, Pullman J, Thompson GR, Powderly W, Tobin EH, Vazquez J, Wring SA, Angulo D, Helou
S, Pappas PG, Mycoses Study Group. MSG-10: a Phase 2 study of oral ibrexafungerp (SCY-078)
following initial echinocandin therapy in non-neutropenic patients with invasive candidiasis.
J Antimicrob Chemother. 2019;74:3056–62.
[205] Hager CL, Larkin EL, Long L, Abidi FZ, Shaw KJ, Ghannoum MA. In vitro and in vivo evaluation of
the antifungal activity of APX001A/APX001 against Candida auris. Antimicrob Agents Chemother.
2018;62(3). Available from:
[206] Zhao Y, Lee MH, Paderu P, Lee A, Jimenez-Ortigosa C, Park S, mansbach R, Shaw KJ, Perlin DS.
Significantly improved pharmacokinetics enhances in vivo efficacy of APX001 against echinocandin and multidrug-resistant Candida isolates in a mouse model of invasive candidiasis. Antimicrob Agents
Chemother. 2018;62(10). Available from: /pmc/articles/PMC6153843/.
[207] Zhao M, Lepak AJ, Marchillo K, Vanhecker J, Sanchez H, Ambrose PG, Andes DR. Apx001
pharmacokinetic/pharmacodynamic target determination against aspergillus fumigatus in an in vivo
model of invasive pulmonary aspergillosis. Antimicrob Agents Chemother. 2019;63(4). Available
[208] Hodges MR, Ople E, Shaw KJ, Mansbach R, Van Mard SJ, Van Hoogdalem EJ, Wedel P, Kramer W.
First-in-human study to assess safety, tolerability and pharmacokinetics of APX001 administered by
intravenous infusion to healthy subjects. Open Forum Infect Dis. 2017;4(1):s526.
[209] Hodges MR, Ople E, Shaw KJ, Mansbach R, Van Mard SJ, Van Hoogdalem EJ, Wedel P, Kramer W.
Phase 1 study to assess safety, tolerability and pharmacokinetics of single and multiple oral doses of
APX001 and to investigate the effect of food on APX001 bioavailabilit.
Open Forum Infect Dis. 2017;4(1):S534.
[210] Stenland CJ, Lis LG, Schendel FJ, Hahn NJ, Smart MA, Miller AL, Von Keitz MG, Gurvich VJ. A
practical and scalable manufacturing process for an antifungal agent, nikkomycin Z. Org Process Res
Dev. 2013;17(2):265–72. Available from:
[211] Rauseo AM, Coler-Reilly A, Larson L, Spec A. Hope on the horizon: Novel fungal treatments in
development. Vol. 7, Open Forum Infectious Diseases. 2020. Available from:
[212] Nix DE, Swezey RR, Hector R, Galgiani JN. Pharmacokinetics of nikkomycin Z after single rising oral
doses. Antimicrob Agents Chemother. 2009;53:2517–21.
[213] Safety and PK of Nikkomycin Z for Coccidioides Pneumonia Treatment. Available.
2019; Available from: t:
[214] Yates CM, Garvey EP, Shaver SR, Schotzinger RJ, Hoekstra WJ. Design and optimization of highly selective,
broad spectrum fungal CYP51 inhibitors. Bioorganic Med Chem Lett. 2017;27(15):3243–8.
Available from:
[215] Schell WA, Jones AM, Garvey EP, Hoekstra WJ, Schotzinger RJ, Alexander BD. Fungal CYP51
inhibitors VT-1161 and VT-1129 exhibit strong in vitro activity against Candida glabrata and C. krusei
isolates clinically resistant to azole and echinocandin antifungal compounds. Antimicrob Agents
Chemother. 2017;61(3). Available from:
[216] Warrilow AGS, Parker JE, Price CL, Garvey EP, Hoekstra WJ, Schotzinger RJ, Wiederhold NP, Nes
WD, Kelly DE, Kelly SL. The tetrazole VT-1161 is a potent inhibitor of Trichophyton rubrum through
its inhibition of T. rubrum CYP51. Antimicrob Agents Chemother. 2017;61(7). Available from:
[217] Wiederhold NP, Najvar LK, Garvey EP, Brand SR, Xu X, Ottinger EA, Alimardanov A, Cradok J,
Behnke M, Hoekstra WJ, Schotzinger RJ, Jaramillo R, Olivo M, Kirkpatrick WR, Patterson T. The
Fungal Cyp51 Inhibitor VT-1129 Is Efficacious in an Experimental Model of Cryptococc


Publish with Nova Science Publishers

We publish over 800 titles annually by leading researchers from around the world. Submit a Book Proposal Now!