Fungal Biofilms 2020

A special issue of Journal of Fungi (ISSN 2309-608X). This special issue belongs to the section "Fungal Cell Biology, Metabolism and Physiology".

Deadline for manuscript submissions: closed (1 October 2020) | Viewed by 36816

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Special Issue Editors


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Guest Editor
1. Associate Laboratory i4HB—Institute for Health and Bioeconomy, University Institute of Health Sciences—CESPU, 4585-116 Gandra, Portugal
2. ALiCE—Associate Laboratory in Chemical Engineering, Faculty of Engineering, LEPABE—Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Porto, Portugal
Interests: biofilms; Candida; AMR; fungal infection; polymicrobial biofilms; alternatives to antifungals
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Department of Molecular Biology and Microbiology, Tufts University, Boston, MA, USA
Interests: medical mycology; fungal biofilms; gastrointestinal colonization; polymicrobial biofilms; fungal-bacterial interactions; Clostridioides difficile; anti-virulence; drug discovery and development

Special Issue Information

Dear Colleagues,

Fungal infections are an important and increasing global threat, carrying not only high morbidity and mortality rates, but also high healthcare costs. Without an effective response, it is predicted that 10 million people will die per year as a result of multidrug-resistant pathogens. A high percentage of the mortalities caused by fungi are known to be biofilm-related.

This Special Issue, “Fungal Biofilms 2020”, is intended to cover the state of fungal biofilm research, from virulence and pathogenicity, to new compounds with antibiofilm and antifungal activity. We welcome reviews and original research articles covering the development/evaluation/validation of recent studies, especially those regarding multidrug resistance.

Sincerely,

Dr. Célia Fortuna Rodrigues
Dr. Jesus A. Romo
Guest Editors

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Keywords

  • fungi
  • infection
  • biofilm
  • Candida
  • Aspergillus
  • Cryptococcus
  • antifungal
  • resistance
  • matrix

Published Papers (11 papers)

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Editorial

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2 pages, 184 KiB  
Editorial
Fungal Biofilms 2020
by Célia F. Rodrigues and Jesus A. Romo
J. Fungi 2021, 7(8), 603; https://doi.org/10.3390/jof7080603 - 26 Jul 2021
Cited by 2 | Viewed by 1593
Abstract
Fungal infections are an important and increasing global threat, carrying not only high morbidity and mortality rates, but also extraordinary healthcare costs [...] Full article
(This article belongs to the Special Issue Fungal Biofilms 2020)

Research

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16 pages, 1327 KiB  
Article
Compounds with Distinct Targets Present Diverse Antimicrobial and Antibiofilm Efficacy against Candida albicans and Streptococcus mutans, and Combinations of Compounds Potentiate Their Effect
by Carmélia Isabel Vitorino Lobo, Ana Carolina Urbano de Araújo Lopes and Marlise Inêz Klein
J. Fungi 2021, 7(5), 340; https://doi.org/10.3390/jof7050340 - 28 Apr 2021
Cited by 18 | Viewed by 2266
Abstract
Candida albicans and Streptococcus mutans interact synergistically in biofilms associated with a severe form of dental caries. Their synergism is driven by dietary sucrose. Thus, it is necessary to devise strategies to hinder the development of those biofilms and prevent cavities. Six compounds [...] Read more.
Candida albicans and Streptococcus mutans interact synergistically in biofilms associated with a severe form of dental caries. Their synergism is driven by dietary sucrose. Thus, it is necessary to devise strategies to hinder the development of those biofilms and prevent cavities. Six compounds [tt-farnesol (sesquiterpene alcohol that decreases the bacterium acidogenicity and aciduricity and a quorum sensing fungal molecule), myricetin (flavonoid that interferes with S. mutans exopolysaccharides production), two 2’-hydroxychalcones and 4’-hydroxychalcone (intermediate metabolites for flavonoids), compound 1771 (inhibitor of lipoteichoic synthase in Gram-positive bacteria)] with targets in both fungus and bacterium and their products were investigated for their antimicrobial and antibiofilm activities against single-species cultures. The compounds and concentrations effective on single-species biofilms were tested alone and combined with or without fluoride to control initial and pre-formed dual-species biofilms. All the selected treatments eliminated both species on initial biofilms. In contrast, some combinations eliminated the bacterium and others the fungus in pre-formed biofilms. The combinations 4’-hydroxychalcone+tt-farnesol+myricetin, 4’-hydroxychalcone+tt-farnesol+fluoride, and all compounds together with fluoride were effective against both species in pre-formed biofilms. Therefore, combinations of compounds with distinct targets can prevent C. albicans and S. mutans dual-species biofilm build-up in vitro. Full article
(This article belongs to the Special Issue Fungal Biofilms 2020)
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12 pages, 1937 KiB  
Article
Candida parapsilosis Colony Morphotype Forecasts Biofilm Formation of Clinical Isolates
by Emilia Gómez-Molero, Iker De-la-Pinta, Jordan Fernández-Pereira, Uwe Groß, Michael Weig, Guillermo Quindós, Piet W. J. de Groot and Oliver Bader
J. Fungi 2021, 7(1), 33; https://doi.org/10.3390/jof7010033 - 7 Jan 2021
Cited by 9 | Viewed by 3271
Abstract
Candida parapsilosis is a frequent cause of fungal bloodstream infections, especially in critically ill neonates or immunocompromised patients. Due to the formation of biofilms, the use of indwelling catheters and other medical devices increases the risk of infection and complicates treatment, as cells [...] Read more.
Candida parapsilosis is a frequent cause of fungal bloodstream infections, especially in critically ill neonates or immunocompromised patients. Due to the formation of biofilms, the use of indwelling catheters and other medical devices increases the risk of infection and complicates treatment, as cells embedded in biofilms display reduced drug susceptibility. Therefore, biofilm formation may be a significant clinical parameter, guiding downstream therapeutic choices. Here, we phenotypically characterized 120 selected isolates out of a prospective collection of 215 clinical C. parapsilosis isolates, determining biofilm formation, major emerging colony morphotype, and antifungal drug susceptibility of the isolates and their biofilms. In our isolate set, increased biofilm formation capacity was independent of body site of isolation and not predictable using standard or modified European Committee on Antimicrobial Susceptibility Testing (EUCAST) drug susceptibility testing protocols. In contrast, biofilm formation was strongly correlated with the appearance of non-smooth colony morphotypes and invasiveness into agar plates. Our data suggest that the observation of non-smooth colony morphotypes in cultures of C. parapsilosis may help as an indicator to consider the initiation of anti-biofilm-active therapy, such as the switch from azole- to echinocandin- or polyene-based strategies, especially in case of infections by potent biofilm-forming strains. Full article
(This article belongs to the Special Issue Fungal Biofilms 2020)
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15 pages, 3847 KiB  
Article
The Membranotropic Peptide gH625 to Combat Mixed Candida albicans/Klebsiella pneumoniae Biofilm: Correlation between In Vitro Anti-Biofilm Activity and In Vivo Antimicrobial Protection
by Angela Maione, Elisabetta de Alteriis, Federica Carraturo, Stefania Galdiero, Annarita Falanga, Marco Guida, Anna Di Cosmo, Valeria Maselli and Emilia Galdiero
J. Fungi 2021, 7(1), 26; https://doi.org/10.3390/jof7010026 - 5 Jan 2021
Cited by 25 | Viewed by 2779
Abstract
The antibiofilm activity of a gH625 analogue was investigated to determine the in vitro inhibition and eradication of a dual-species biofilm of Candida albicans and Klebsiella pneumoniae, two leading opportunistic pathogens responsible for several resistant infections. The possibility of effectively exploiting this [...] Read more.
The antibiofilm activity of a gH625 analogue was investigated to determine the in vitro inhibition and eradication of a dual-species biofilm of Candida albicans and Klebsiella pneumoniae, two leading opportunistic pathogens responsible for several resistant infections. The possibility of effectively exploiting this peptide as an alternative anti-biofilm strategy in vivo was assessed by the investigation of its efficacy on the Galleria mellonella larvae model. Results on larvae survival demonstrate a prophylactic efficacy of the peptide towards the infection of each single microorganism but mainly towards the co-infection. The expression of biofilm-related genes in vivo showed a possible synergy in virulence when these two species co-exist in the host, which was effectively prevented by the peptide. These findings provide novel insights into the treatment of medically relevant bacterial–fungal interaction. Full article
(This article belongs to the Special Issue Fungal Biofilms 2020)
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11 pages, 761 KiB  
Article
A Screen for Small Molecules to Target Candida albicans Biofilms
by Matthew B. Lohse, Craig L. Ennis, Nairi Hartooni, Alexander D. Johnson and Clarissa J. Nobile
J. Fungi 2021, 7(1), 9; https://doi.org/10.3390/jof7010009 - 27 Dec 2020
Cited by 5 | Viewed by 2789
Abstract
The human fungal pathogen Candida albicans can form biofilms on biotic and abiotic surfaces, which are inherently resistant to antifungal drugs. We screened the Chembridge Small Molecule Diversity library containing 30,000 “drug-like” small molecules and identified 45 compounds that inhibited biofilm formation. These [...] Read more.
The human fungal pathogen Candida albicans can form biofilms on biotic and abiotic surfaces, which are inherently resistant to antifungal drugs. We screened the Chembridge Small Molecule Diversity library containing 30,000 “drug-like” small molecules and identified 45 compounds that inhibited biofilm formation. These 45 compounds were then tested for their abilities to disrupt mature biofilms and for combinatorial interactions with fluconazole, amphotericin B, and caspofungin, the three antifungal drugs most commonly prescribed to treat Candida infections. In the end, we identified one compound that moderately disrupted biofilm formation on its own and four compounds that moderately inhibited biofilm formation and/or moderately disrupted mature biofilms only in combination with either caspofungin or fluconazole. No combinatorial interactions were observed between the compounds and amphotericin B. As members of a diversity library, the identified compounds contain “drug-like” chemical backbones, thus even seemingly “weak hits” could represent promising chemical starting points for the development and the optimization of new classes of therapeutics designed to target Candida biofilms. Full article
(This article belongs to the Special Issue Fungal Biofilms 2020)
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13 pages, 1095 KiB  
Article
Gene Expression Analysis of Non-Clinical Strain of Aspergillus fumigatus (LMB-35Aa): Does Biofilm Affect Virulence?
by Teresa D. Rebaza, Yvette Ludeña, Ilanit Samolski and Gretty K. Villena
J. Fungi 2020, 6(4), 376; https://doi.org/10.3390/jof6040376 - 18 Dec 2020
Cited by 4 | Viewed by 2391
Abstract
Aspergillus fumigatus LMB-35Aa, a saprophytic fungus, was used for cellulase production through biofilms cultures. Since biofilms usually favor virulence in clinical strains, the expression of the related genes of the LMB 35-Aa strain was analyzed by qPCR from the biomass of planktonic cultures [...] Read more.
Aspergillus fumigatus LMB-35Aa, a saprophytic fungus, was used for cellulase production through biofilms cultures. Since biofilms usually favor virulence in clinical strains, the expression of the related genes of the LMB 35-Aa strain was analyzed by qPCR from the biomass of planktonic cultures and biofilms developed on polyester cloth and polystyrene microplates. For this, virulence-related genes reported for the clinical strain Af293 were searched in A. fumigatus LMB 35-Aa genome, and 15 genes were identified including those for the synthesis of cell wall components, hydrophobins, invasins, efflux transporters, mycotoxins and regulators. When compared with planktonic cultures at 37 °C, invasin gene calA was upregulated in both types of biofilm and efflux transporter genes mdr4 and atrF were predominantly upregulated in biofilms on polystyrene, while aspHs and ftmA were upregulated only in biofilms formed on polyester. Regarding the transcription regulators, laeA was downregulated in biofilms, and medA did not show a significant change. The effect of temperature was also evaluated by comparing the biofilms grown on polyester at 37 vs. 28 °C. Non-significant changes at the expression level were found for most genes evaluated, except for atrF, gliZ and medA, which were significantly downregulated at 37 °C. According to these results, virulence appears to depend on the interaction of several factors in addition to biofilms and growth temperature. Full article
(This article belongs to the Special Issue Fungal Biofilms 2020)
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16 pages, 2415 KiB  
Article
Susceptibility of the Candida haemulonii Complex to Echinocandins: Focus on Both Planktonic and Biofilm Life Styles and a Literature Review
by Lívia S. Ramos, Laura N. Silva, Marta H. Branquinha and André L. S. Santos
J. Fungi 2020, 6(4), 201; https://doi.org/10.3390/jof6040201 - 1 Oct 2020
Cited by 4 | Viewed by 1842
Abstract
Candida haemulonii complex (C. haemulonii, C. duobushaemulonii and C. haemulonii var. vulnera) is well-known for its resistance profile to different available antifungal drugs. Although echinocandins are the most effective class of antifungal compounds against the C. haemulonii species complex, clinical [...] Read more.
Candida haemulonii complex (C. haemulonii, C. duobushaemulonii and C. haemulonii var. vulnera) is well-known for its resistance profile to different available antifungal drugs. Although echinocandins are the most effective class of antifungal compounds against the C. haemulonii species complex, clinical isolates resistant to caspofungin, micafungin and anidulafungin have already been reported. In this work, we present a literature review regarding the effects of echinocandins on this emergent fungal complex. Published data has revealed that micafungin and anidulafungin were more effective than caspofungin against the species forming the C. haemulonii complex. Subsequently, we investigated the susceptibilities of both planktonic and biofilm forms of 12 Brazilian clinical isolates of the C. haemulonii complex towards caspofungin and micafungin (anidulafungin was unavailable). The planktonic cells of all the fungal isolates were susceptible to both of the test echinocandins. Interestingly, echinocandins caused a significant reduction in the biofilm metabolic activity (viability) of almost all fungal isolates (11/12, 91.7%). Generally, the biofilm biomasses were also affected (reduction range 20–60%) upon exposure to caspofungin and micafungin. This is the first report of the anti-biofilm action of echinocandins against the multidrug-resistant opportunistic pathogens comprising the C. haemulonii complex, and unveils the therapeutic potential of these compounds. Full article
(This article belongs to the Special Issue Fungal Biofilms 2020)
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17 pages, 3199 KiB  
Article
Biofilm Formed by Candida haemulonii Species Complex: Structural Analysis and Extracellular Matrix Composition
by Lívia S. Ramos, Thaís P. Mello, Marta H. Branquinha and André L. S. Santos
J. Fungi 2020, 6(2), 46; https://doi.org/10.3390/jof6020046 - 3 Apr 2020
Cited by 15 | Viewed by 3060
Abstract
Candida haemulonii species complex (C. haemulonii, C. duobushaemulonii, and C. haemulonii var. vulnera) has emerged as opportunistic, multidrug-resistant yeasts able to cause fungemia. Previously, we showed that C. haemulonii complex formed biofilm on polystyrene. Biofilm is a well-known virulence [...] Read more.
Candida haemulonii species complex (C. haemulonii, C. duobushaemulonii, and C. haemulonii var. vulnera) has emerged as opportunistic, multidrug-resistant yeasts able to cause fungemia. Previously, we showed that C. haemulonii complex formed biofilm on polystyrene. Biofilm is a well-known virulence attribute of Candida spp. directly associated with drug resistance. In the present study, the architecture and the main extracellular matrix (ECM) components forming the biofilm over polystyrene were investigated in clinical isolates of the C. haemulonii complex. We also evaluated the ability of these fungi to form biofilm on catheters used in medical arena. The results revealed that all fungi formed biofilms on polystyrene after 48 h at 37 °C. Microscopic analyses demonstrated a dense network of yeasts forming the biofilm structure, with water channels and ECM. Regarding ECM, proteins and carbohydrates were the main components, followed by nucleic acids and sterols. Mature biofilms were also detected on late bladder (siliconized latex), nasoenteric (polyurethane), and nasogastric (polyvinyl chloride) catheters, with the biomasses being significantly greater than on polystyrene. Collectively, our results demonstrated the ability of the C. haemulonii species complex to form biofilm on different types of inert surfaces, which is an incontestable virulence attribute associated with devices-related candidemia in hospitalized individuals. Full article
(This article belongs to the Special Issue Fungal Biofilms 2020)
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Review

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13 pages, 342 KiB  
Review
Plant Preparations and Compounds with Activities against Biofilms Formed by Candida spp.
by Tomasz M. Karpiński, Marcin Ożarowski, Agnieszka Seremak-Mrozikiewicz, Hubert Wolski and Artur Adamczak
J. Fungi 2021, 7(5), 360; https://doi.org/10.3390/jof7050360 - 5 May 2021
Cited by 28 | Viewed by 4322
Abstract
Fungi from the genus Candida are very important human and animal pathogens. Many strains can produce biofilms, which inhibit the activity of antifungal drugs and increase the tolerance or resistance to them as well. Clinically, this process leads to persistent infections and increased [...] Read more.
Fungi from the genus Candida are very important human and animal pathogens. Many strains can produce biofilms, which inhibit the activity of antifungal drugs and increase the tolerance or resistance to them as well. Clinically, this process leads to persistent infections and increased mortality. Today, many Candida species are resistant to drugs, including C. auris, which is a multiresistant pathogen. Natural compounds may potentially be used to combat multiresistant and biofilm-forming strains. The aim of this review was to present plant-derived preparations and compounds that inhibit Candida biofilm formation by at least 50%. A total of 29 essential oils and 16 plant extracts demonstrate activity against Candida biofilms, with the following families predominating: Lamiaceae, Myrtaceae, Asteraceae, Fabaceae, and Apiacae. Lavandula dentata (0.045–0.07 mg/L), Satureja macrosiphon (0.06–8 mg/L), and Ziziphora tenuior (2.5 mg/L) have the best antifungal activity. High efficacy has also been observed with Artemisia judaica, Lawsonia inermis, and Thymus vulgaris. Moreover, 69 plant compounds demonstrate activity against Candida biofilms. Activity in concentrations below 16 mg/L was observed with phenolic compounds (thymol, pterostilbene, and eugenol), sesquiterpene derivatives (warburganal, polygodial, and ivalin), chalconoid (lichochalcone A), steroidal saponin (dioscin), flavonoid (baicalein), alkaloids (waltheriones), macrocyclic bisbibenzyl (riccardin D), and cannabinoid (cannabidiol). The above compounds act on biofilm formation and/or mature biofilms. In summary, plant preparations and compounds exhibit anti-biofilm activity against Candida. Given this, they may be a promising alternative to antifungal drugs. Full article
(This article belongs to the Special Issue Fungal Biofilms 2020)
13 pages, 293 KiB  
Review
Fungal Quorum-Sensing Molecules: A Review of Their Antifungal Effect against Candida Biofilms
by Renátó Kovács and László Majoros
J. Fungi 2020, 6(3), 99; https://doi.org/10.3390/jof6030099 - 2 Jul 2020
Cited by 41 | Viewed by 5325
Abstract
The number of effective therapeutic strategies against biofilms is limited; development of novel therapies is urgently needed to treat a variety of biofilm-associated infections. Quorum sensing is a special form of microbial cell-to-cell communication that is responsible for the release of numerous extracellular [...] Read more.
The number of effective therapeutic strategies against biofilms is limited; development of novel therapies is urgently needed to treat a variety of biofilm-associated infections. Quorum sensing is a special form of microbial cell-to-cell communication that is responsible for the release of numerous extracellular molecules, whose concentration is proportional with cell density. Candida-secreted quorum-sensing molecules (i.e., farnesol and tyrosol) have a pivotal role in morphogenesis, biofilm formation, and virulence. Farnesol can mediate the hyphae-to-yeast transition, while tyrosol has the opposite effect of inducing transition from the yeast to hyphal form. A number of questions regarding Candida quorum sensing remain to be addressed; nevertheless, the literature shows that farnesol and tyrosol possess remarkable antifungal and anti-biofilm effect at supraphysiological concentration. Furthermore, previous in vitro and in vivo data suggest that they may have a potent adjuvant effect in combination with certain traditional antifungal agents. This review discusses the most promising farnesol- and tyrosol-based in vitro and in vivo results, which may be a foundation for future development of novel therapeutic strategies to combat Candida biofilms. Full article
(This article belongs to the Special Issue Fungal Biofilms 2020)
19 pages, 810 KiB  
Review
Unraveling How Candida albicans Forms Sexual Biofilms
by Austin M. Perry, Aaron D. Hernday and Clarissa J. Nobile
J. Fungi 2020, 6(1), 14; https://doi.org/10.3390/jof6010014 - 15 Jan 2020
Cited by 10 | Viewed by 5625
Abstract
Biofilms, structured and densely packed communities of microbial cells attached to surfaces, are considered to be the natural growth state for a vast majority of microorganisms. The ability to form biofilms is an important virulence factor for most pathogens, including the opportunistic human [...] Read more.
Biofilms, structured and densely packed communities of microbial cells attached to surfaces, are considered to be the natural growth state for a vast majority of microorganisms. The ability to form biofilms is an important virulence factor for most pathogens, including the opportunistic human fungal pathogen Candida albicans. C. albicans is one of the most prevalent fungal species of the human microbiota that asymptomatically colonizes healthy individuals. However, C. albicans can also cause severe and life-threatening infections when host conditions permit (e.g., through alterations in the host immune system, pH, and resident microbiota). Like many other pathogens, this ability to cause infections depends, in part, on the ability to form biofilms. Once formed, C. albicans biofilms are often resistant to antifungal agents and the host immune response, and can act as reservoirs to maintain persistent infections as well as to seed new infections in a host. The majority of C. albicans clinical isolates are heterozygous (a/α) at the mating type-like (MTL) locus, which defines Candida mating types, and are capable of forming robust biofilms when cultured in vitro. These “conventional” biofilms, formed by MTL-heterozygous (a/α) cells, have been the primary focus of C. albicans biofilm research to date. Recent work in the field, however, has uncovered novel mechanisms through which biofilms are generated by C. albicans cells that are homozygous or hemizygous (a/a, a/Δ, α/α, or α/Δ) at the MTL locus. In these studies, the addition of pheromones of the opposite mating type can induce the formation of specialized “sexual” biofilms, either through the addition of synthetic peptide pheromones to the culture, or in response to co-culturing of cells of the opposite mating types. Although sexual biofilms are generally less robust than conventional biofilms, they could serve as a protective niche to support genetic exchange between mating-competent cells, and thus may represent an adaptive mechanism to increase population diversity in dynamic environments. Although conventional and sexual biofilms appear functionally distinct, both types of biofilms are structurally similar, containing yeast, pseudohyphal, and hyphal cells surrounded by an extracellular matrix. Despite their structural similarities, conventional and sexual biofilms appear to be governed by distinct transcriptional networks and signaling pathways, suggesting that they may be adapted for, and responsive to, distinct environmental conditions. Here we review sexual biofilms and compare and contrast them to conventional biofilms of C. albicans. Full article
(This article belongs to the Special Issue Fungal Biofilms 2020)
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