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- •Foreword
- •Preface
- •Contents
- •Editors and Contributors
- •About the Editors
- •Contributors
- •1.1 Introduction
- •1.2 Conventional Methods
- •1.2.1 Microscopy
- •1.2.2 Culture
- •1.2.3 Germ Tube Test
- •1.2.5 Carbohydrate Assimilation Test
- •1.2.6 Nitrogen Assimilation Test
- •1.2.7 Carbohydrate Fermentation Test
- •1.2.8 Urease Test
- •1.2.9 Tween 80 Opacity Test
- •1.3 Nonculture-Based Conventional Methods
- •1.3.1 Serological Methods
- •1.3.1.2 ß-d-Glucan
- •1.3.1.3 C. albicans Germ Tube Antibody Assay (CAGTA)
- •1.4 Nucleic Acid-Based Detection
- •1.4.1 Polymerase Chain Reaction (PCR)
- •1.4.3 Peptide Nucleic Acid FISH (PNA-FISH)
- •1.4.4 PCR-Based Innovative Diagnosis
- •1.4.5 FilmArray System
- •1.4.6 Sepsis Flow Chip
- •1.4.7 ePlex System
- •1.4.8 The T2 Candida Assay
- •1.5 Rapid Identification Systems
- •1.5.1 Manual Rapid Identification System
- •1.5.1.1 The API System
- •1.5.1.2 The VITEK System
- •1.5.2 Automatic Rapid Identification System
- •1.5.2.1 MALDI-TOF MS
- •1.5.2.2 The MALDI Sepsityper IVD Kit
- •1.5.2.3 The BioFire FilmArray BCID2 Panel
- •1.5.2.4 The Accelerate Pheno BC Panel
- •1.6 Advanced Diagnostics
- •1.6.2 Biosensor-Based Tests
- •1.6.3 Next-Generation Sequencing (NGS)
- •1.7 Conclusion
- •References
- •2.1 Introduction
- •2.2.1.2 Echinocandins
- •First-Generation Echinocandin
- •Second-Generation Echinocandin
- •2.2.1.3 Other Cell Wall Inhibitors
- •2.2.2.1 Azoles
- •Imidazole
- •Triazole
- •Second-Generation Azole
- •Third-Generation Azole
- •2.2.2.2 Polyenes
- •Other Polyene Under Development
- •2.2.2.3 Allylamines
- •2.2.3 Flucytosine
- •2.3 Conclusion
- •References
- •3.1 Introduction
- •3.2.1 Control Diet
- •3.2.3 Toxification
- •3.2.4 Alternative Treatments
- •3.3.1 Prophylaxis
- •3.3.2 Preemptive Therapies
- •3.3.3 Empirical Therapies
- •3.4 Therapeutic Approach
- •3.4.1 Azoles
- •3.4.2 Echinocandins
- •3.4.3 Polyenes
- •References
- •4.1 Introduction
- •4.3 Eukarya Domain
- •4.4.1 Cryptococcus
- •4.4.2 Aspergillus
- •4.4.3 Mucorales
- •4.4.4 Candida
- •4.5.1 Candida albicans
- •4.5.2 Morphogenesis
- •4.5.3 Pathogenesis
- •4.5.4 Adherence
- •4.5.5 Morphological Switching
- •4.5.6 Invasion
- •4.6 Induced Endocytosis
- •4.7 Active Penetration
- •4.8.2 Biofilm Formation
- •4.8.4.1 Antifungals
- •4.8.4.2 Antifungal Resistance
- •References
- •5.1 Introduction
- •5.2.3.1 Serum
- •5.2.3.2 Low Nitrogen
- •5.2.3.5 Carbon Source
- •5.2.3.6 pH
- •5.2.3.7 N-acetylglucosamine (GlcNAc)
- •5.2.3.8 Quorum Sensing Molecule
- •5.5.5 Surface Colonization Factor1 (SCF1)
- •5.5.6 Other Putative Adhesins
- •5.6.1 Phospholipases
- •5.6.2 Proteinases
- •5.6.3 Hemolysins
- •5.6.4 Lipases
- •5.7 Secreted Cytolytic Peptide: Candidalysin
- •5.5.1 ALS Family
- •5.5.2 HWP Adhesin
- •5.5.3 HYR/IFF Family
- •5.5.4 EPA Family
- •5.9.2 Low Molecular Weight Hsp/Small Heat Shock Proteins
- •5.10.1 Amino Acid/Nitrogen Metabolism
- •5.10.1.1 Amino Acid Sensing Pathway
- •5.12.1.1 Glycolysis
- •5.12.1.2 Gluconeogenesis
- •5.12.1.3 Glyoxylate Cycle
- •5.12.1.4 Fatty Acid Oxidation
- •5.12.3.2 Iron Metabolism
- •5.12.3.3 Candida Iron Transport
- •5.12.3.4 Reductive System
- •5.12.3.5 Siderophore Uptake System
- •5.12.3.6 Haemoglobin-Iron Uptake System
- •5.13.2 Zinc Metabolism
- •References
- •6.1 Introduction
- •6.2 Morphological Switching
- •6.3 Phenotypic Switching
- •6.4 Biofilm Formation
- •6.5 Metabolic Flexibility
- •6.8.1 Hemolysin
- •6.8.2 Phospholipases
- •6.8.3 Proteinase
- •6.8.4 Candidalysin
- •6.12 Conclusion
- •References
- •7.1 Introduction
- •7.2.4 Polymorphism
- •7.2.5.1 Secreted Aspartyl Proteinases
- •7.2.5.2 Phospholipase
- •7.2.6 Calcineurin-Signalling Pathway
- •7.2.7 Ion Homeostasis
- •7.2.7.1 Iron
- •7.2.7.2 Copper
- •7.2.8.1 Capsule
- •7.2.8.2 Melanin
- •7.2.8.3 Heat Shock Proteins
- •7.3 Conclusions
- •References
- •8.1 Introduction
- •8.4.1 ATP-Binding Cassette (ABC) Transporters
- •8.4.2 Major Facilitator Superfamily (MFS) Transporter
- •8.5.1 Biofilm Architecture Among Candida Species
- •References
- •9.1 Introduction
- •References
- •10.1 Introduction
- •10.3 Biofilm
- •10.5 Adherence
- •10.6 Maturation
- •10.8 Dispersion
- •10.11 Animal Models
- •10.18 Photodynamic Therapy
- •References
- •11.1 Introduction
- •11.9 Concluding Remarks
- •References
- •12.1 Introduction
- •12.2 Epidemiology
- •12.3.1 Humoral Response
- •12.3.2 Cellular Immunity
- •12.4 Virulence Factors
- •12.6.1 Fluconazole
- •12.6.2 Polyenes
- •12.6.3 Echinocandins
- •12.7 Drug Resistance
- •12.8 Future Prospects
- •12.9 Conclusions
- •References
- •13.1 Introduction
- •13.4 Translation Research
- •13.4.1 Disease-Oriented Translational Research
- •13.4.2 Lab-Oriented Translational Research
- •13.4.3 Patient-Oriented Translational Research
- •13.5 Conclusion
- •References
- •14.1 Introduction
- •14.2.3 Cutaneous Aspergillosis
- •14.2.4 Ocular Aspergillosis
- •14.2.5 Aspergillus Endocarditis
- •14.2.6 Aspergillus Osteomyelitis
- •14.2.7 Sinus Aspergillosis
- •14.3.2 Histopathology
- •14.3.3 Serological
- •14.3.4 Breath Testing
- •14.3.5 Monoclonal Antibody (mAbs)-Mediated Methods
- •14.4.1 Conventional Therapeutics
- •14.4.1.1 Azoles
- •14.4.1.2 Polyenes
- •14.4.1.3 Echinocandins
- •14.4.1.4 Fluoropyrimidines
- •14.5 Nonconventional Therapeutics
- •14.5.1 Vaccine
- •14.5.2 Monoclonal Antibodies (mAbs)
- •14.5.3 Nanotechnology-Based Therapeutics
- •14.5.4 Immune Therapy
- •14.5.5 Combination Therapy
- •14.8 Conclusion
- •References
- •15: Aspergillus Therapeutics: Future Agents
- •15.1 Introduction
- •15.2.1 Fosmanogepix
- •15.2.2 Ibrexafungerp
- •15.2.3 Olorofim
- •15.2.4 Opelconazole
- •15.2.5 Rezafungin
- •15.2.6 MGCD290
- •15.2.7 Tetrazoles (VT-1129/VT-1161/VT-1598)
- •15.2.8 Nikkomycin Z
- •15.2.9 VL-2397
- •15.2.10 T-2307/ATI-2307
- •15.2.11 Encochleated Amphotericin-B
- •15.2.12 SUBA-Itraconazole
- •15.2.13 Immunotherapy
- •15.2.14 Drug Repurposing
- •References
- •16.1 Introduction
- •16.2 Antifungal Agents
- •16.2.1 Azoles
- •16.2.2 Posaconazole
- •16.2.3 Isavuconazole
- •16.2.4 SUBA—Itraconazole
- •16.2.5 Nanovoriconazole
- •16.2.6 Adverse Effects
- •16.3 Liposomal Amphotericin B (LAMB)
- •16.3.1 Echinocandins
- •16.4 Combination Antifungal Therapy
- •16.5 Therapeutic Drug Monitoring (TDM)
- •16.5.1 Azole-Resistant Aspergillus Spp.
- •16.6 Guideline Recommendations
- •16.10 Conclusion
- •References
- •17.1 Introduction
- •17.3 Potent Antifungal Molecules Under Investigations
- •References
- •19.2 Host–A. fumigatus Interactions
- •19.3.1 Hydrophobicity or Rodlet Layer
- •19.3.2 Conidiation
- •19.3.3 DHN Melanin
- •19.3.5 Siderophores
- •19.3.6 Biofilm Formation
- •19.4 Conclusion
- •References

9 Biolm Formation inCandida Species
251
adequate attention. This transition is not unconnected to diverse genes and regulatory proteins, many of which are yet to be explored.
Furthermore, our understanding of biolm development and regulatory mecha-
nisms remains incomplete despite recent advancements. The regulatory circuit of
biolms is not clearly and completely understood. Furthermore, there is a lack of
detailed information about the temporal regulation of biolms, particularly the
mechanisms guiding cells through later stages of the life cycle. The production and
organization of different cell types within a biolm are not fully grasped. An intriguing question is whether biolm cells exhibit ‘cell memory.’ If there is a memory,
does this memory persist after the cells have been dispersed and biolm established
in a new environment? Additionally, the functions of diverse genes that are induced
during biolm formation remain unknown. All these represent a signicant gap that
needs to be lled.
Furthermore, despite the research efforts made thus far, no specic drugs for
Candida spp. target biolms. Currently, treating infections associated with biolm
is an uphill task. However, understanding biolm formation processes in Candida
and its association with resistance to antifungals in all Candida spp. is crucial for
devising a more effective treatment strategy. The necessity for antifungal drugs with
efcacy against biolm formation cannot be overstated. Furthermore, an approach
that weakens Candida biolm initiation and production of the matrix could make
treating infections associated with this phenotype easy to handle. While various
biomaterials show promise (Fioriti etal. 2022; Mba etal. 2022), repression of some
key virulence steps like hyphae formation (Lee etal. 2019) also has potential. In a
recent investigation, the use of enzymes and botanical extracts was promising
(Jensen etal. 2023). However, combination therapy could also be more effective
(Tits etal. 2020; Vitale 2021; Fioriti etal. 2022) as every single method has advantages and disadvantages. Moreover, several recent investigations have attempted to
look into different approaches for eliminating and inhibiting biolm among Candida
species (Acosta etal. 2020; Mba and Nweze 2020a, b; Aydin etal. 2023; do Rosário
Esteves Guimarães etal. 2023; Putra Wigianto etal. 2023). For more insight on the
emerging approaches for overcoming Candida infections due to biolms, readers
are encouraged to read a recent review by Kulshrestha and Gupta (2023).
Overall, more studies are needed to understand the differences in biolm forma-
tion among the various Candida species completely and to understand how the
entire biolm process is controlled and regulated. Deciphering the fundamental
mechanisms and factors implicated in biolm formation and their association with
virulence and resistance is vital. This is important to unveil new targets for developing strategies to manage and prevent infection associated with biolms. Moreover,
future studies should also look at the molecular interactions between Candida and
other species and host immunological signatures during polymicrobial infections
involving biolm.
Conict of Interest The authors declare that they have no conict of interest.

252
M. I. Elibe and N. E. Innocent
References
Acosta LD, Pérez-Camacho O, Acosta R, Escobar DM, Gallardo CA, Sánchez-Vargas LO (2020)
Reduction of Candida albicans biolm formation by coating polymethyl methacrylate denture
bases with a photopolymerized lm. J Prosthet Dent 124(5):605–613
Al-Fattani MA, Douglas LJ (2006) Biolm matrix of Candida albicans and Candida tropicalis:
chemical composition and role in drug resistance. J Med Microbiol 55:999–1008. https://doi.
org/10.1099/jmm.0.46569- 0
Ambe NF, Longdoh NA, Tebid P, Bobga TP, Nkfusai CN, Ngwa SB, Nsai FS, Cumber SN (2020)
The prevalence, risk factors and antifungal sensitivity pattern of oral candidiasis in HIV/AIDS
patients in Kumba District Hospital, South West Region, Cameroon. Pan Afr Med J 36:23.
https://doi.org/10.11604/pamj.2020.36.23.18202
Andes D, Nett J, Oschel P, Albrecht R, Marchillo K, Pitula A (2004) Development and character-
ization of an invivo central venous catheter Candida albicans biolm model. Infect Immun
72(10):6023–6031. https://doi.org/10.1128/IAI.72.10.6023- 6031.2004
Araújo D, Henriques M, Silva S (2017) Portrait of Candida species biolm regulatory network
genes. Trends Microbiol 25:62–75. https://doi.org/10.1016/j.tim.2016.09.004
Atriwal T, Azeem K, Husain FM, Hussain A, Khan MN, Alajmi MF, Abid M (2021) Mechanistic
understanding of Candida albicans biolm formation and approaches for its inhibition. Front
Microbiol 12:638609. https://doi.org/10.3389/fmicb.2021.638609
Aydin M, Ozturk A, Duran T, Ozmen UO, Sumlu E, Ayan EB, Korucu EN (2023) In vitro antifun-
gal and antibiolm activities of novel sulfonyl hydrazone derivatives against Candida spp. J
Mycol Med 33(1):101327
Balducci E, Papi F, Capialbi DE, Del Bino L (2023) Polysaccharides’ structures and functions
in biolm architecture of antimicrobial-resistant (AMR) pathogens. Int J Mol sci 24(4):4030.
https://doi.org/10.3390/ijms24044030
Barantsevich N, Barantsevich E (2022) Diagnosis and treatment of invasive candidiasis.
Antibiotics 11:718
Bhattacharya S, Sae-Tia S, Fries BC (2020) Candidiasis and mechanisms of antifungal resistance.
Antibiotics 9:312
Bizerra FC, Nakamura CV, de Poersch C, Estivalet Svidzinski TI, Borsato Quesada RM, Goldenberg
S etal (2008) Characteristics of biolm formation by Candida tropicalis and antifungal resistance. FEMS Yeast Res 8:442–450. https://doi.org/10.1111/j.1567- 1364.2007.00347.x
Branco J, Miranda IM, Rodrigues AG (2023) Candida parapsilosis virulence and antifungal resis-
tance mechanisms: a comprehensive review of key determinants. J Fungi (Basel, Switzerland)
9(1):80. https://doi.org/10.3390/jof9010080
Cámara M, Green W, MacPhee CE etal (2022) Economic signicance of biolms: a multidisci-
plinary and cross-sectoral challenge. NPJ Biolms Microbiomes 8:42. https://doi.org/10.1038/
s41522- 022- 00306- y
Cavalheiro M, Teixeira MC (2018) Candida biolms: threats, challenges, and promising strate-
gies. Front Med 5:28. https://doi.org/10.3389/fmed.2018.00028
Chandra J, Kuhn DM, Mukherjee PK, Hoyer LL, McCormick T, Ghannoum MA (2001) Biolm
formation by the fungal pathogen Candida albicans: development, architecture, and drug resistance. J Bacteriol 183:5385–5394. https://doi.org/10.1128/JB.183.18.5385- 5394.2001
Cleary IA, Lazzell AL, Monteagudo C, Thomas DP, Stephen P (2012) BRG1 and NRG1 form a
novel feedback circuit regulating C. albicans hyphal formation and virulence. Mol Microbiol
85:557–573. https://doi.org/10.1111/j.1365- 2958.2012.08127.x
Codda G, Willison E, Magnasco L, Morici P, Giacobbe DR, Mencacci A, Marini D, Mikulska
M, Bassetti M, Marchese A, Di Pilato V (2023) In vivo evolution to echinocandin resistance
and increasing clonal heterogeneity in Candida auris during a difcult-to-control hospital outbreak, Italy, 2019 to 2022. Euro Surveill 28(14):2300161. https://doi.org/10.2807/1560- 7917.
ES.2023.28.14.2300161

9 Biolm Formation inCandida Species
Costa-de-Oliveira S, Rodrigues AG (2020) Candida albicans antifungal resistance and tolerance in
bloodstream infections: the triad yeast-host-antifungal. Microorganisms 8(2):154. https://doi.
org/10.3390/microorganisms8020154
Czajka KM, Venkataraman K, Brabant-Kirwan D, Santi SA, Verschoor C, Appanna VD, Singh
R, Saunders DP, Tharmalingam S (2023) Molecular mechanisms associated with antifungal
resistance in pathogenic Candida species. Cells 12(22):2655
Davey ME, O’toole GA (2000) Microbial biolms: from ecology to molecular genetics. Microbiol
Mol Biol Rev 64:847–867
de Groot PWJ, Bader O, de Boer AD, Weig M, Chauhan N (2013) Adhesins in human fungal
pathogens: glue with plenty of stick. Eukaryot Cell 12:470–481. https://doi.org/10.1128/
EC.00364- 12
de Melo CC, de Sousa BR, da Costa GL, Oliveira MME, de Lima-Neto RG (2023) Colonized
patients by Candida auris: third and largest outbreak in Brazil and impact of biolm formation.
Front Cell Infect Microbiol 13:1033707
Denega I, d’Enfert C, Bachellier-Bassi S (2019) Candida albicans biolms are generally devoid of
persister cells. Antimicrob Agents Chemother 63(5):e01979–e01918. https://doi.org/10.1128/
AAC.01979- 18
Desai JV, Mitchell AP (2015) Candida albicans biolm development and its genetic control.
Microbiol Spectr 3(3). https://doi.org/10.1128/microbiolspec.MB- 0005- 2014
Díaz-García J, Machado M, Alcalá L, Reigadas E, Sánchez-Carrillo C, Pérez-Ayala A, Gómez-
García de la Pedrosa E, González-Romo F, Merino P, Cuétara MS, García-Esteban C,
Quiles-Melero I, Zurita ND, Muñoz-Algarra M, Durán-Valle MT, Martínez-Quintero GA,
Sánchez-García A, Muñoz P, Escribano P, Guinea J et al (2023) Antifungal resistance in
Candida spp within the intra-abdominal cavity: study of resistance acquisition in patients
with serial isolates. Clin Microbiol Infect 29(12):1604.e1–1604.e6. https://doi.org/10.1016/j.
cmi.2023.08.021
do Rosário Esteves Guimarães C, de Freitas HF, Barros TF (2023) Candida albicans antibiolm
molecules: analysis based on inhibition and eradication studies. Braz J Microbiol 54(1):37–52
Eichelberger KR, Cassat JE (2021) Metabolic adaptations during Staphylococcus aureus and
Candida albicans co-infection. Front Immunol 12:797550
Eix EF, Nett JE (2020) How biolm growth affects Candida-host interactions. Front Microbiol
11:1437. https://doi.org/10.3389/fmicb.2020.01437
Estivill D, Arias A, Torres-Lana A, Carrillo-Muñoz AJ, Arévalo MP (2011) Biolm formation
by ve species of Candida on three clinical materials. J Microbiol Methods 86(2):238–242.
https://doi.org/10.1016/j.mimet.2011.05.019
Fernandes L, Costa R, Henriques M, Rodrigues ME (2023) Simulated vaginal uid: Candida
resistant strains’ biolm characterization and vapor phase of essential oil effect. J Mycol Med
33(1):101329
Fernández-Pereira J, Alvarado M, Gómez-Molero E, Dekker HL, Blázquez-Muñoz MT, Eraso E,
Bader O, de Groot PWJ (2021) Characterization of Awp14, a novel cluster III adhesin identied
in a high biolm-forming Candida glabrata isolate. Front Cell Infect Microbiol 11:790465.
https://doi.org/10.3389/fcimb.2021.790465
Finkel JS, Xu W, Huang D, Hill EM, Desai JV, Woolford CA etal (2012) Portrait of Candida
albicans adherence regulators. PLoS Pathog 8:e1002525. https://doi.org/10.1371/journal.
ppat.1002525
Fioriti S, Brescini L, Pallotta F, Canovari B, Morroni G, Barchiesi F (2022) Antifungal combina-
tions against Candida species: from bench to bedside. J Fungi 8(10):1077
Fourie R, Pohl CH (2019) Beyond antagonism: the interaction between Candida species and
Pseudomonas aeruginosa. J Fungi 5(2):34. https://doi.org/10.3390/jof5020034
Fox EP, Bui CK, Nett JE, Hartooni N, Mui MC, Andes DR etal (2015) An expanded regulatory net-
work temporally controls Candida albicans biolm formation. Mol Microbiol 96:1226–1239.
https://doi.org/10.1111/mmi.13002
Freitas VAQ, Santos AS, Zara ALSA, Costa CR, Godoy CSM, Soares RBA, Ataídes FS, Silva
MDRR (2023) Distribution and antifungal susceptibility proles of Candida species iso-
253

254
lated from people living with HIV/AIDS in a public hospital in Goiânia, GO, Brazil. Braz J
Microbiol 54(1):125–133. https://doi.org/10.1007/s42770- 022- 00851- w
Galdiero E, de Alteriis E, De Natale A etal (2020) Eradication of Candida albicans persister
cell biolm by the membranotropic peptide gH625. Sci Rep 10:5780. https://doi.org/10.1038/
s41598- 020- 62746- w
Govrins M, Lass-Flörl C (2023) Candida parapsilosis complex in the clinical setting. Nat Rev
Microbiol 22(1):46–59. https://doi.org/10.1038/s41579- 023- 00961- 8
Gulati M, Nobile CJ (2016) Candida albicans biolms: development, regulation, and molecular
mechanisms. Microbes Infect 18(5):310–321. https://doi.org/10.1016/j.micinf.2016.01.002
Haddadin Y, Annamaraju P, Regunath H (2023) Central line–associated blood stream infections
[Updated 2022 Nov 26]. In: StatPearls [Internet]. StatPearls, Treasure Island. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK430891/
Haiko J, Saeedi B, Bagger G, Karpati F, Özenci V (2019) Coexistence of Candida species and
bacteria in patients with cystic brosis. Eur J Clin Microbiol Infect Dis 38(6):1071–1077
Hassan Y, Chew SY, Than LTL (2021) Candida glabrata: pathogenicity and resistance mechanisms
for adaptation and survival. J Fungi (Basel) 7(8):667. https://doi.org/10.3390/jof7080667
Hawser SP, Douglas LJ (1995) Resistance of Candida albicans biolms to antifungal agents
invitro. Antimicrob Agents Chemother 39:2128–2131. https://doi.org/10.1128/AAC.39.9.2128
Hernday AD, Lohse MB, Fordyce PM, Nobile CJ, DeRisi JL, Johnson AD (2013) Structure of
the transcriptional network controlling white-opaque switching in Candida albicans. Mol
Microbiol 90:22–35
Homann OR, Dea J, Noble SM, Johnson AD (2009) A phenotypic prole of the Candida albicans
regulatory network. PLoS Genet 5:e1000783. https://doi.org/10.1371/journal.pgen.1000783
Hoyer LL, Payne TL, Bell M, Myers AM, Scherer S (1998) Candida albicans ALS3 and insights
into the nature of the ALS gene family. Curr Genet 33:451–459. https://doi.org/10.1007/
s002940050359
Huang YH, Lee YH, Lin CJ, Hsu LH, Chen YL (2023) Deubiquitination module is critical for oxi-
dative stress response and biolm formation in Candida glabrata. Med Mycol 61(10):myad099.
https://doi.org/10.1093/mmy/myad099
Jenkinson HF, Douglas LJ (2002) Interactions between Candida species and bacteria in mixed
infections. In: Brogden KA, Guthmiller JM (eds) Polymicrobial diseases. ASM, Washington,
DC.Chapter 18. Available from: https://www.ncbi.nlm.nih.gov/books/NBK2486/
Jensen GS, Cruickshank D, Hamilton DE (2023) Disruption of established bacterial and fungal
biolms by a blend of enzymes and botanical extracts. J Microbiol Biotechnol 33(6):715–723
Junqueira JC, Mylonakis E (2023) Editorial: Candida biolms. Front Microbiol 13:1128600
Kamran M, Calcagno AM, Findon H, Bignell E, Jones MD, Warn P, Hopkins P, Denning DW,
Butler G, Rogers T, Mühlschlegel FA, Haynes K (2004) Inactivation of transcription factor
gene ACE2in the fungal pathogen Candida glabrata results in hypervirulence. Eukaryot Cell
3(2):546–552. https://doi.org/10.1128/EC.3.2.546- 552.2004
Karkowska-Kuleta J, Kulig K, Bras G, Stelmaszczyk K, Surowiec M, Kozik A, Karnas E,
Barczyk-Woznicka O, Zuba-Surma E, Pyza E, Rapala-Kozik M (2023) Candida albicans
biolm-derived extracellular vesicles are involved in the tolerance to caspofungin, biolm
detachment, and fungal proteolytic activity. J Fungi (Basel, Switzerland) 9(11):1078. https://
doi.org/10.3390/jof9111078
Kaur J, Nobile CJ (2023) Antifungal drug-resistance mechanisms in Candida biolms. Curr Opin
Microbiol 71:102237. https://doi.org/10.1016/j.mib.2022.102237
Kolter R, Greenberg EP (2006) Microbial sciences: the supercial life of microbes. Nature
441:300–302
Kuhn DM, Chandra J, Mukherjee PK, Ghannoum MA (2002a) Comparison of biolms formed
by Candida albicans and Candida parapsilosis on bioprosthetic surfaces. Infect Immun
70:878–888. https://doi.org/10.1128/IAI.70.2.878- 888.2002
Kuhn DM, George T, Chandra J, Mukherjee PK, Ghannoum MA (2002b) Antifungal sus-
ceptibility of Candida biolms: unique efcacy of amphotericin B lipid formulations and
M. I. Elibe and N. E. Innocent

9 Biolm Formation inCandida Species
echinocandins. Antimicrob Agents Chemother 46:1773–1780. https://doi.org/10.1128/
AAC.46.6.1773- 1780.2002
Kulshrestha A, Gupta P (2023) Combating polymicrobial biolm: recent approaches. Folia
Microbiol (Praha) 68(4):495–505
Kumari A, Tripathi AH, Gautam P, Gahtori R, Pande A, Singh Y, Madan T, Upadhyay SK
(2021) Adhesins in the virulence of opportunistic fungal pathogens of human. Mycology
12(4):296–324. https://doi.org/10.1080/21501203.2021.1934176
Lane S, Birse C, Zhou S, Matson R, Liu H (2001a) DNA array studies demonstrate convergent
regulation of virulence factors by Cph1, Cph2, and Efg1in Candida albicans. J Biol Chem
276:48988–48996. https://doi.org/10.1074/jbc.M104484200
Lane S, Zhou S, Pan T, Dai Q, Liu H (2001b) The basic helix-loop-helix transcription factor
Cph2 regulates hyphal development in Candida albicans partly via Tec1. Mol Cell Biol
21:6418–6428. https://doi.org/10.1128/MCB.21.19.6418- 6428.2001
Lattif AA, Mukherjee PK, Chandra J, Swindell K, Lockhart SR, Diekema DJ et al (2010)
Characterization of biolms formed by Candida parapsilosis, C. metapsilosis, and C. orthopsilosis. Int J Med Microbiol 300:265–270. https://doi.org/10.1016/j.ijmm.2009.09.001
Lee JH, Kim YG, Khadke SK, Yamano A, Watanabe A, Lee J (2019) Inhibition of biolm forma-
tion by Candida albicans and polymicrobial microorganisms by nepodin via hyphal-growth
suppression. ACS Infect Dis 5(7):1177–1187
Lewis K (2007) Persister cells, dormancy and infectious disease. Nat Rev Microbiol 5:48–56.
https://doi.org/10.1038/nrmicro1557
Lindsay AK, Hogan DA (2014) Candida albicans: molecular interactions with Pseudomonas aeru-
ginosa and Staphylococcus aureus. Fungal Biol Rev 28:85–96
Liu S, Jiang L, Miao H, Lv Y, Zhang Q, Ma M, Duan W, Huang Y, Wei X (2022) Autophagy regula-
tion of ATG13 and ATG27 on biolm formation and antifungal resistance in Candida albicans.
Biofouling 38(9):926–939. https://doi.org/10.1080/08927014.2022.2153332
Lohse MB, Gulati M, Johnson AD, Nobile CJ (2018) Development and regulation of single-and
multispecies Candida albicans biolms. Nat Rev Microbiol 16:19–31
Lucas C, Silva C (2023) The extracellular matrix of yeasts: a key player in the microbial biology
change of paradigm. Front Biosci (Elite Ed) 15(2):13. https://doi.org/10.31083/j.fbe1502013
Lueyar TK, Karygianni L, Attin T, Thurnheer T (2023) Dynamic interactions between Candida
albicans and different streptococcal species in a multispecies oral biolm. MicrobiologyOpen
12(5):e1381. https://doi.org/10.1002/mbo3.1381
Macias-Paz IU, Pérez-Hernández S, Tavera-Tapia A, Luna-Arias JP, Guerra-Cárdenas JE, Reyna-
Beltrán E (2023) Candida albicans the main opportunistic pathogenic fungus in humans. Rev
Argent Microbiol 55(2):189–198
Maiti P, Ghorai P, Ghosh S, Kamthan M, Tyagi RK, Datta A (2015) Mapping of functional domains
and characterization of the transciption factor Cph1 that mediate morphogenesis in Candida
albicans. Fungal Genet Biol 83:45–57. https://doi.org/10.1016/j.fgb.2015.08.004
Malinovská Z, Čonková E, Váczi P (2023) Biolm formation in medically important Candida spe-
cies. J Fungi 9(10):955. https://doi.org/10.3390/jof9100955
Massey J, Zarnowski R, Andes D (2023) Role of the extracellular matrix in Candida biolm anti-
fungal resistance. FEMS Microbiol Rev 47(6):fuad059. https://doi.org/10.1093/femsre/fuad059
Mba IE, Nweze EI (2020a) The use of nanoparticles as alternative therapeutic agents against
Candida infections: an up-to-date overview and future perspectives. World J Microbiol
Biotechnol 36(11):163
Mba IE, Nweze EI (2020b) Mechanism of Candida pathogenesis: revisiting the vital drivers. Eur J
Clin Microbiol Infect Dis 39:1797–1819. https://doi.org/10.1007/s10096- 020- 03912- w
Mba IE, Nweze EI, Eze EA, Anyaegbunam ZKG (2022) Genome plasticity in Candida albicans:
a cutting-edge strategy for evolution, adaptation, and survival. Infect Genet Evol 99:105256
McCall AD, Pathirana RU, Prabhakar A et al (2019) Candida albicans biolm development
is governed by cooperative attachment and adhesion maintenance proteins. NPJ Biolms
Microbiomes 5:21. https://doi.org/10.1038/s41522- 019- 0094- 5
255

256
Mirghani R, Saba T, Khaliq H, Mitchell J, Do L, Chambi L, Diaz K, Kennedy T, Alkassab K,
Huynh T, Elmi M, Martinez J, Sawan S, Rijal G (2022) Biolms: formation, drug resistance
and alternatives to conventional approaches. AIMS Microbiol 8(3):239–277. https://doi.
org/10.3934/microbiol.2022019
Mitchell KF, Zarnowski R, Andes DR (2016) The extracellular matrix of fungal biolms. Adv Exp
Med Biol 931:21–35. https://doi.org/10.1007/5584_2016_6
Modrezewka B, Kurnatowski P (2015) Adherence of Candida sp. to host tissues and cells as one
of its pathogenicity features. Ann Parasitol 61:3–9
Moreno-Martínez AE, Gómez-Molero E, Sánchez-Virosta P, Dekker HL, de Boer A, Eraso E,
Bader O, de Groot PWJ (2021) High biolm formation of non-smooth Candida parapsilo-
sis correlates with increased incorporation of GPI-modied wall adhesins. Pathogens (Basel,
Switzerland) 10(4):493. https://doi.org/10.3390/pathogens10040493
Ni L, Bruce C, Hart C, Leigh-Bell J, Gelperin D, Umansky L etal (2009) Dynamic and complex
transcription factor binding during an inducible response in yeast. Genes Dev 23:1351–1363
Nobile CJ, Johnson AD (2015) Candida albicans biolms and human disease. Annu Rev Microbiol
69:71–92. https://doi.org/10.1146/annurev- micro- 091014- 104330
Nobile CJ, Andes DR, Nett JE, Smith FJ, Yue F, Phan QT et al (2006) Critical role of Bcr1-
dependent adhesins in C. albicans biolm formation invitro and invivo. PLoS Pathog 2:e63.
https://doi.org/10.1371/journal.ppat.0020063
Nobile CJ, Schneider HA, Nett JE, Sheppard DC, Filler SG, Andes DR, Mitchell AP (2008)
Complementary adhesin function in C. albicans biolm formation. Curr Biol 18(14):1017–1024.
https://doi.org/10.1016/j.cub.2008.06.034
Nobile CJ, Fox EP, Nett JE, Sorrells TR, Mitrovich QM, Hernday AD etal (2013) A recently
evolved transcriptional network controls biolm development in Candida albicans. Cell
148:126–138. https://doi.org/10.1016/j.cell.2011.10.048
Oyardi O, Demir ES, Alkan B, Komec S, Genc GE, Aygun G, Teke L, Turan D, Erturan Z,
Savage PB, Guzel CB (2023) Phenotypic investigation of virulence factors, susceptibility to
Ceragenins, and the impact of biolm formation on drug efcacy in Candida auris isolates
from Türkiye. J Fungi (Basel) 9(10):1026
Pais P, Costa C, Pires C, Shimizu K, Chibana H, Teixeira MC (2016) Membrane proteome-wide
response to the antifungal drug clotrimazole in Candida glabrata: role of the transcription
factor CgPdr1 and the drug:H+ antiporters CgTpo1_1 and CgTpo1_2. Mol Cell Proteomics
15:57–72. https://doi.org/10.1074/mcp.M114.045344
Pathak AK, Sharma S, Shrivastva P (2012) Multispecies biolm of Candida albicans and non-
Candida albicans Candida species on acrylic substrate. J Appl Oral Sci 20(1):70–75. https://
doi.org/10.1590/s1678- 77572012000100013
Pereira R, dos Santos Fontenelle RO, de Brito EHS etal (2021) Biolm of Candida albicans:
formation, regulation and resistance. J Appl Microbiol 131:11–22. https://doi.org/10.1111/
jam.14949
Pokhrel S, Boonmee N, Tulyaprawat O etal (2022) Assessment of biolm formation by Candida
albicans strains isolated from hemocultures and their role in pathogenesis in the zebrash
model. J Fungi 8:1014. https://doi.org/10.3390/jof8101014
Ponde NO, Lortal L, Ramage G, Naglik JR, Richardson JP (2021) Candida albicans biolms and
polymicrobial interactions. Crit Rev Microbiol 47:91–111
Purohit D, Gajjar D (2022) Tec1 and Ste12 transcription factors play a role in adaptation to low pH
stress and biolm formation in the human opportunistic fungal pathogen Candida glabrata. Int
Microbiol 25(4):789–802. https://doi.org/10.1007/s10123- 022- 00264- 7
Putra Wigianto AY, Ishida Y, Iwawaki Y, Goto T, Watanabe M, Sekine K, Hamada K, Murakami K,
Fujii H, Ichikawa T (2023) 2-methacryloyloxyethyl phosphorylcholine polymer treatment prevents Candida albicans biolm formation on acrylic resin. J Prosthodont Res 67(3):384–391
Rai LS, Chauvel M, Permal E, d’Enfert C, Bachellier-Bassi S (2023) Transcript proling reveals
the role of PDB1, a subunit of the pyruvate dehydrogenase complex, in Candida albicans biolm formation. Res Microbiol 174(3):104014
M. I. Elibe and N. E. Innocent

9 Biolm Formation inCandida Species
Raj K, Rishi P, Shukla G, Rudramurhty SM, Mongad DS, Kaur A (2022) Possible contribution of
alternative transcript isoforms in mature biolm growth phase of Candida glabrata. Indian J
Microbiol 62(4):583–601. https://doi.org/10.1007/s12088- 022- 01036- 7
Ramage G, Bachmann S, Patterson TF, Wickes BL, López-ribot JL (2002) Investigation of mul-
tidrug efux pumps in relation to uconazole resistance in Candida albicans biolms. J
Antimicrob Chemother 49:973–980. https://doi.org/10.1093/jac/dkf049
Ramage G, Saville SP, Thomas DP, López-Ribot JL (2005) Candida biolms: an update. Eukaryot
Cell 4(4):633–638. https://doi.org/10.1128/EC.4.4.633- 638.2005
Ramage G, Borghi E, Rodrigues CF, Kean R, Williams C, Lopez-Ribot J (2023) Our current clinical
understanding of Candida biolms: where are we two decades on? APMIS 131(11):636–653
Rho J, Shin JH, Song JW, Park MR, Kee SJ, Jang SJ etal (2004) Molecular investigation of two
consecutive nosocomial clusters of Candida tropicalis candiduria using pulsed-eld gel elec-
trophoresis. J Microbiol 42:80–86
Rodrigues CF, Rodrigues ME, Silva S, Henriques M (2017) Candida glabrata biolms: how far
have we come? J Fungi (Basel) 3(1):11. https://doi.org/10.3390/jof3010011
Rodriguez DL, Quail MM, Hernday AD, Nobile CJ (2020) Transcriptional circuits regulating
developmental processes in Candida albicans. Front Cell Infect Microbiol 10:605711. https://
doi.org/10.3389/fcimb.2020.605711
Salvatori O, Kumar R, Metcalfe S, Vickerman M, Kay JG, Edgerton M (2020) Bacteria modify
Candida albicans hypha formation, microcolony properties, and survival within macrophages.
mSphere 5(4):e00689-20
Santos R, Costa C, Mil-Homens D, Romão D, de Carvalho CC, Pais P etal (2017) The multidrug
resistance transporters CgTpo1_1 and CgTpo1_2 play a role in virulence and biolm formation
in the human pathogen Candida glabrata. Cell Microbiol 19:1–13. https://doi.org/10.1111/
cmi.12686
Sathi FA, Alam MM, Paul SK, Nasrin SA, Ahmed S, Haque N, Khan MS, Mamun AA, Khan
S, Arafa P (2023) Species identication and antifungal susceptibility pattern of Candida isolates in patients with vulvovaginitis from Mymensingh, Bangladesh. Mymensingh Med J
32(3):638–643
Schulze A, Mitterer F, Pombo JP, Schild S (2021) Biolms by bacterial human pathogens: clinical
relevance- development, composition and regulation—therapeutical strategies. Microb Cell
8(2):28–56. https://doi.org/10.15698/mic2021.02.741
Sellam A, Tebbji F, Nantel A (2009) Role of Ndt80p in sterol metabolism regulation and azole resis-
tance in Candida albicans. Eukaryot Cell 8:1174–1183. https://doi.org/10.1128/EC.00074- 09
Sellam A, Askew C, Epp E, Tebbji F, Mullick A, Whiteway M etal (2010) Role of transcrip-
tion factor CaNdt80p in cell separation, hyphal growth, and virulence in Candida albicans.
Eukaryot Cell 9:634–644. https://doi.org/10.1128/EC.00325- 09
Seneviratne CJ, Jin L, Samaranayake LP (2008) Biolm lifestyle of Candida: a mini review. Oral
Dis 14:582–590. https://doi.org/10.1111/j.1601- 0825.2007.01424.x
Seneviratne CJ, Wang Y, Jin L, Abiko Y, Samaranayake LP (2010) Proteomics of drug resis-
tance in Candida glabrata biolms. Proteomics 10:1444–1454. https://doi.org/10.1002/
pmic.200900611
Shi C, Liu J, Li W, Zhao Y, Meng L, Xiang M (2019) Expression of uconazole resistance-
associated genes in biolm from 23 clinical isolates of Candida albicans. Braz J Microbiol
50(1):157–163. https://doi.org/10.1007/s42770- 018- 0009- 2
Sikora A, Zahra F (2023) Nosocomial Infections. [Updated 2023 Apr 27]. In: StatPearls [Internet].
StatPearls Publishing, Treasure Island. Available from: https://www.ncbi.nlm.nih.gov/books/
NBK559312/
Silva S, Henriques M, Martins A, Oliveira R, Williams D, Azeredo J (2009) Biolms of non-
Candida albicans Candida species: quantication, structure and matrix composition. Med
Mycol 47:681–689. https://doi.org/10.3109/13693780802549594
Silva S, Henriques M, Hayes A, Oliveira R, Azeredo J, Williams DW (2011) Candida glabrata and
Candida albicans co-infection of an invitro oral epithelium. J Oral Pathol Med 40(5):421–427
257

258
Sims CR, Ostrosky-zeichner L, Rex JH (2005) Invasive candidiasis in immunocompromised hos-
pitalized patients. Arch Med Res 36:660–671. https://doi.org/10.1016/j.arcmed.2005.05.015
Song JW, Shin JH, Kee SJ, Kim SH, Shin MG, Suh SP etal (2009) Expression of CgCDR1,
CgCDR2, and CgERG11in Candida glabrata biolms formed by bloodstream isolates. Med
Mycol 47:545–548. https://doi.org/10.1080/13693780802210726
Szekely J, Rakchang W, Rattanaphan P, Kositpantawong N (2023) Fluconazole and echinocan-
din resistance of Candida species in invasive candidiasis at a university hospital during preCOVID- 19 and the COVID-19 outbreak. Epidemiol Infect 151:e146. https://doi.org/10.1017/
S0950268823001346
Tits J, Cammue BPA, Thevissen K (2020) Combination therapy to treat fungal biolm-based
infections. Int J Mol Sci 21(22):8873
Toyofuku M, Inaba T, Kiyokawa T, Obana N, Yawata Y, Nomura N (2016) Environmental factors
that shape biolm formation. Biosci Biotechnol Biochem 80(1):7–12. https://doi.org/10.108
0/09168451.2015.1058701
Vázquez-Franco N, Gutiérrez-Escobedo G, Juárez-Reyes A, Orta-Zavalza E, Castaño I, De Las
Peñas A (2022) Candida glabrata Hst1-Rfm1-Sum1 complex evolved to control virulence-
related genes. Fungal Genet Biol 159:103656. https://doi.org/10.1016/j.fgb.2021.103656
Verstrepen KJ, Klis FM (2006) Flocculation, adhesion and biolm formation in yeasts. Mol
Microbiol 60:5–15. https://doi.org/10.1111/j.1365- 2958.2006.05072.x
Vestby LK, Grønseth T, Simm R, Nesse LL (2020) Bacterial biolm and its role in the pathogen-
esis of disease. Antibiotics (Basel) 9(2):59. https://doi.org/10.3390/antibiotics9020059
Vitale RG (2021) Role of antifungal combinations in difcult to treat Candida infections. J Fungi
(Basel) 7(9):731
Vitális E, Nagy F, Tóth Z, Forgács L, Bozó A, Kardos G, Majoros L, Kovács R (2020) Candida
biolm production is associated with higher mortality in patients with Candidaemia. Mycoses
63:352–360. https://doi.org/10.1111/myc.13049
Vitiello A, Ferrara F, Boccellino M, Ponzo A, Cimmino C, Comberiati E, Zovi A, Clemente S,
Sabbatucci M (2023) Antifungal drug resistance: an emergent health threat. Biomedicines
11(4):1063. https://doi.org/10.3390/biomedicines11041063
Wheeler RT, Kombe D, Agarwala SD, Fink GR (2008) Dynamic, morphotype-specic Candida
albicans β-glucan exposure during infection and drug treatment. PLoS Pathog 4:e1000227.
https://doi.org/10.1371/journal.ppat.1000227
Wijaya M, Halleyantoro R, Kalumpiu JF (2023) Biolm: the invisible culprit in catheter-induced
candidemia. AIMS Microbiol 9(3):467–485. https://doi.org/10.3934/microbiol.2023025
Witchley JN, Penumetcha P, Abon NV, Woolford CA, Mitchell AP, Noble SM (2019) Candida
albicans morphogenesis programs control the balance between gut commensalism and invasive infection. Cell Host Microbe 25(3):432–443.e6
Wuyts J, Van Dijck P, Holtappels M (2018) Fungal persister cells: the basis for recalcitrant infec-
tions? PLoS Pathog 14(10):e1007301. https://doi.org/10.1371/journal.ppat.1007301
Xiao J, Zeng Y, Rustchenko E, Huang X, Wu TT, Falsetta ML (2022) Dual transcriptome
of Streptococcus mutans and Candida albicans interplay in biolms. J Oral Microbiol
15(1):2144047
Xu Z, Huang T, Min D et al (2022) Regulatory network controls microbial biolm develop-
ment, with Candida albicans as a representative: from adhesion to dispersal. Bioengineered
13:253–267. https://doi.org/10.1080/21655979.2021.1996747
Yamin DH, Husin A, Harun A (2021) Risk factors of Candida parapsilosis catheter-related blood-
stream infection. Front Public Health 9:631865. https://doi.org/10.3389/fpubh.2021.631865
Yazdanpanah S, Ahmadi M, Zare Z, Nikoupour H, Arabsheybani S, Jabrodini A, Eghtedarnejad E,
Chamanpara P, Geramizadeh B, Anbardar MH, Malekizadeh Z, Gashtasebi M, Mohsenzadeh
M, Shaekhani M, Zomorodian K (2023) Assessment of risk factors and clinical outcomes
in hospitalized COVID-19 patients with Candida spp. co-infections: species distribution and
antifungal susceptibility patterns of isolates. Mycopathologia 188(1–2):9–20
Yin W, Wang Y, Liu L, He J (2019) Biolms: the microbial “protective clothing” in extreme envi-
ronments. Int J Mol Sci 20(14):3423
M. I. Elibe and N. E. Innocent

9 Biolm Formation inCandida Species
Zarnowski R, Westler WM, Lacmbouh GA, Marita JM, Bothe JR, Bernhardt J et al (2014)
Novel entries in a fungal biolm matrix encyclopedia. MBio 5:e01333–e01314. https://doi.
org/10.1128/mBio.01333- 14
Zhao JT, Chen KZ, Liu JY, Li WH, Wang YZ, Wang LL, Xiang MJ (2022) FLO8 deletion
leads to decreased adhesion and virulence with downregulated expression of EPA1, EPA6,
and EPA7 in Candida glabrata. Braz J Microbiol 53(2):727–738. https://doi.org/10.1007/
s42770- 022- 00703- 7
Zuo XS, Liu Y, Cai X, Zhan L, Hu K (2021) Association of different Candida species with catheter-
related candidemia, and the potential antifungal treatments against their adhesion properties and
biolm-forming capabilities. J Clin Lab Anal 35(4):e23738. https://doi.org/10.1002/jcla.23738
259

Dissemination ofCandida auris Biofilms:
AMedical Abrosia
GarimaGangwar, BhartiSingh, andRekhaPuria
Abstract
Candida auris is a newly discovered, multidrug-resistant fungal pathogen and
poses a global health risk. There has been a dramatic increase in the number of
cases and transmission in hospitals especially amongst patients hospitalized in
ICU and with suppressed immune systems. The pathobiology of this fungus is
inadequately studied. Apparently, this fungus needs to form biolms in order to
spread infection and evade medication therapy. Biolms have important function in the virulence and pathogenesis of C. auris. Transcriptome analysis
revealed that C. auris upregulates adhesin proteins PGA52, PGA26, IFF4, and
CSA1 during the formation and maintenance of biolms. Major facilitator
superfamily proteins MDR1 and RDC3 and ABC transporter proteins such as
CDR1, SNQ2, and YHD3 are induced during biolm formation. A brief overview of the biology of C. auris biolm is given in this chapter. It contains details
on several models created to comprehend biolms and the various signalling
pathways with the possibility of new therapeutic targets for the removal of the
pathogenic biolm.
10
Keywords
Candida auris · Virulence · Biolm · Antifungal resistance
G. Gangwar · B. Singh · R. Puria (*)
School of Biotechnology, Gautam Buddha University, Greater Noida, Uttar Pradesh, India
e-mail: btphd2020003@gbu.ac.in; rpuria@gbu.ac.in
© The Author(s), under exclusive license to Springer Nature Singapore Pte
Ltd. 2024
S. Hameed, P. Vijayaraghavan (eds.), Recent Advances in Human Fungal
Diseases, https://doi.org/10.1007/978-981-97-4909-6_10
261
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