Fungal and Polymicrobial Biofilms

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Biofilm".

Deadline for manuscript submissions: closed (28 February 2022) | Viewed by 36402

Special Issue Editor


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Guest Editor
Department of Molecular and Cell Biology, University of California Merced, Merced, CA 95343, USA
Interests: microbial communities; Candida; biofilms
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Biofilms are the predominant growth state of many microorganisms. In the most general sense, a biofilm is a community of adherent cells with properties that are distinct from those of free-floating (planktonic) cells. The National Institutes of Health estimates that biofilms are responsible, in one way or another, for over 80% of all microbial infections.

There is a significant body of mechanistic knowledge on how bacteria form biofilms; however, much less is known about how fungi form biofilms. The focus of this Special Issue is on understanding biofilms formed by fungal species, with an emphasis on those species that cause infection in humans. This includes but is not limited to Candida albicans, one of the major fungal biofilm-formers in humans, as well as interacting fungal and bacterial species that together form polymicrobial biofilms.

I invite you to submit research articles, review articles, and short communications on topics pertaining to fungal biofilms and polymicrobial biofilms. As a Guest Editor of this Special Issue, I look forward to reviewing your submissions and to publishing your work.

Prof. Dr. Clarissa J. Nobile
Guest Editor

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Keywords

  • biofilm formation
  • fungi
  • Candida
  • polymicrobial biofilms
  • interspecies interactions

Published Papers (9 papers)

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Research

Jump to: Review

11 pages, 966 KiB  
Article
Host Age and Denture Wearing Jointly Contribute to Oral Colonization with Intrinsically Azole-Resistant Yeasts in the Elderly
by Klaus-Peter Wojak, Gertrud F. Ungermann, Ichsan Ichsan, Emilia Gomez-Molero, Klaus Jung, Michael Weig, Friedemann Nauck, Dirk Ziebolz, Yvonne Gräser, Roland Nau, Uwe Groß, Bernd Alt-Epping and Oliver Bader
Microorganisms 2021, 9(8), 1627; https://doi.org/10.3390/microorganisms9081627 - 30 Jul 2021
Viewed by 2280
Abstract
In elderly patients, several morbidities or medical treatments predisposing for fungal infections occur at a higher frequency, leading to high mortality and morbidity in this vulnerable patient group. Often, this is linked to an innately azole-resistant yeast species such as Candida glabrata or [...] Read more.
In elderly patients, several morbidities or medical treatments predisposing for fungal infections occur at a higher frequency, leading to high mortality and morbidity in this vulnerable patient group. Often, this is linked to an innately azole-resistant yeast species such as Candida glabrata or C. krusei. Additionally, host age per se and the wearing of dentures have been determined to influence the mix of colonizing species and, consequently, the species distribution of invasive fungal infections. Since both old age and the wearing of dentures are two tightly connected parameters, it is still unclear which of them is the main contributor. Here, we performed a cross-sectional study on a cohort (N = 274) derived from three groups of healthy elderly, diseased elderly, and healthy young controls. With increasing host age, the frequency of oral colonization by a non-albicans Candida species, mainly by C. glabrata, also increased, and the wearing of dentures predisposed for colonization by C. glabrata irrespectively of host age. Physically diseased hosts, on the other hand, were more frequently orally colonized by C. albicans than by other yeasts. For both C. albicans and C. glabrata, isolates from the oral cavity did not generally display an elevated biofilm formation capacity. In conclusion, intrinsically azole-drug-resistant, non-albicans Candida yeasts are more frequent in the oral cavities of the elderly, and fungal cells not contained in biofilms may predispose for subsequent systemic infection with these organisms. This warrants further exploration of diagnostic procedures, e.g., before undergoing elective abdominal surgery or when using indwelling devices on this patient group. Full article
(This article belongs to the Special Issue Fungal and Polymicrobial Biofilms)
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20 pages, 2504 KiB  
Article
Visible Lights Combined with Photosensitizing Compounds Are Effective against Candida albicans Biofilms
by Priyanka Bapat, Gurbinder Singh and Clarissa J. Nobile
Microorganisms 2021, 9(3), 500; https://doi.org/10.3390/microorganisms9030500 - 26 Feb 2021
Cited by 18 | Viewed by 4445
Abstract
Fungal infections are increasing in prevalence worldwide, especially in immunocompromised individuals. Given the emergence of drug-resistant fungi and the fact that there are only three major classes of antifungal drugs available to treat invasive fungal infections, there is a need to develop alternative [...] Read more.
Fungal infections are increasing in prevalence worldwide, especially in immunocompromised individuals. Given the emergence of drug-resistant fungi and the fact that there are only three major classes of antifungal drugs available to treat invasive fungal infections, there is a need to develop alternative therapeutic strategies effective against fungal infections. Candida albicans is a commensal of the human microbiota that is also one of the most common fungal pathogens isolated from clinical settings. C. albicans possesses several virulence traits that contribute to its pathogenicity, including the ability to form drug-resistant biofilms, which can make C. albicans infections particularly challenging to treat. Here, we explored red, green, and blue visible lights alone and in combination with common photosensitizing compounds for their efficacies at inhibiting and disrupting C. albicans biofilms. We found that blue light inhibited biofilm formation and disrupted mature biofilms on its own and that the addition of photosensitizing compounds improved its antibiofilm potential. Red and green lights, however, inhibited biofilm formation only in combination with photosensitizing compounds but had no effects on disrupting mature biofilms. Taken together, these results suggest that photodynamic therapy may be an effective non-drug treatment for fungal biofilm infections that is worthy of further exploration. Full article
(This article belongs to the Special Issue Fungal and Polymicrobial Biofilms)
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17 pages, 3015 KiB  
Article
Anti-Biofilm Activity of Cannabidiol against Candida albicans
by Mark Feldman, Ronit Vogt Sionov, Raphael Mechoulam and Doron Steinberg
Microorganisms 2021, 9(2), 441; https://doi.org/10.3390/microorganisms9020441 - 20 Feb 2021
Cited by 37 | Viewed by 5560
Abstract
Candida albicans is a common fungal pathogen in humans. Biofilm formation is an important virulence factor of C. albicans infections. We investigated the ability of the plant-derived cannabidiol (CBD) to inhibit the formation and removal of fungal biofilms. Further, we evaluated its mode [...] Read more.
Candida albicans is a common fungal pathogen in humans. Biofilm formation is an important virulence factor of C. albicans infections. We investigated the ability of the plant-derived cannabidiol (CBD) to inhibit the formation and removal of fungal biofilms. Further, we evaluated its mode of action. Our findings demonstrate that CBD exerts pronounced time-dependent inhibitory effects on biofilm formation as well as disruption of mature biofilm at a concentration range below minimal inhibitory and fungicidal concentrations. CBD acts at several levels. It modifies the architecture of fungal biofilm by reducing its thickness and exopolysaccharide (EPS) production accompanied by downregulation of genes involved in EPS synthesis. It alters the fungal morphology that correlated with upregulation of yeast-associated genes and downregulation of hyphae-specific genes. Importantly, it represses the expression of C. albicans virulence-associated genes. In addition, CBD increases ROS production, reduces the intracellular ATP levels, induces mitochondrial membrane hyperpolarization, modifies the cell wall, and increases the plasma membrane permeability. In conclusion, we propose that CBD exerts its activity towards C. albicans biofilm through a multi-target mode of action, which differs from common antimycotic agents, and thus can be explored for further development as an alternative treatment against fungal infections. Full article
(This article belongs to the Special Issue Fungal and Polymicrobial Biofilms)
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23 pages, 2399 KiB  
Article
Candida albicans as an Essential “Keystone” Component within Polymicrobial Oral Biofilm Models?
by Tracy Young, Om-Alkhir Alshanta, Ryan Kean, David Bradshaw, Jonathan Pratten, Craig Williams, Chris Woodall, Gordon Ramage and Jason L. Brown
Microorganisms 2021, 9(1), 59; https://doi.org/10.3390/microorganisms9010059 - 28 Dec 2020
Cited by 23 | Viewed by 4110
Abstract
Background: Existing standardized biofilm assays focus on simple mono-species or bacterial-only models. Incorporating Candida albicans into complex biofilm models can offer a more appropriate and relevant polymicrobial biofilm for the development of oral health products. Aims: This study aimed to assess [...] Read more.
Background: Existing standardized biofilm assays focus on simple mono-species or bacterial-only models. Incorporating Candida albicans into complex biofilm models can offer a more appropriate and relevant polymicrobial biofilm for the development of oral health products. Aims: This study aimed to assess the importance of interkingdom interactions in polymicrobial oral biofilm systems with or without C. albicans, and test how these models respond to oral therapeutic challenges in vitro. Materials and Methods: Polymicrobial biofilms (two models containing 5 and 10 bacterial species, respectively) were created in parallel in the presence and absence of C. albicans and challenged using clinically relevant antimicrobials. The metabolic profiles and biomasses of these complex biofilms were estimated using resazurin dye and crystal violet stain, respectively. Quantitative PCR was utilized to assess compositional changes in microbial load. Additional assays, for measurements of pH and lactate, were included to monitor fluctuations in virulence “biomarkers.” Results: An increased level of metabolic activity and biomass in the presence of C. albicans was observed. Bacterial load was increased by more than a factor of 10 in the presence of C. albicans. Assays showed inclusion of C. albicans impacted the biofilm virulence profiles. C. albicans did not affect the biofilms’ responses to the short-term incubations with different treatments. Conclusions: The interkingdom biofilms described herein are structurally robust and exhibit all the hallmarks of a reproducible model. To our knowledge, these data are the first to test the hypothesis that yeasts may act as potential “keystone” components of oral biofilms. Full article
(This article belongs to the Special Issue Fungal and Polymicrobial Biofilms)
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19 pages, 3056 KiB  
Article
Filling the Void: An Optimized Polymicrobial Interkingdom Biofilm Model for Assessing Novel Antimicrobial Agents in Endodontic Infection
by Sumaya Abusrewil, Jason L. Brown, Christopher D. Delaney, Mark C. Butcher, Ryan Kean, Dalia Gamal, J. Alun Scott, William McLean and Gordon Ramage
Microorganisms 2020, 8(12), 1988; https://doi.org/10.3390/microorganisms8121988 - 14 Dec 2020
Cited by 3 | Viewed by 3471
Abstract
There is a growing realization that endodontic infections are often polymicrobial, and may contain Candida spp. Despite this understanding, the development of new endodontic irrigants and models of pathogenesis remains limited to mono-species biofilm models and is bacterially focused. The purpose of this [...] Read more.
There is a growing realization that endodontic infections are often polymicrobial, and may contain Candida spp. Despite this understanding, the development of new endodontic irrigants and models of pathogenesis remains limited to mono-species biofilm models and is bacterially focused. The purpose of this study was to develop and optimize an interkingdom biofilm model of endodontic infection and use this to test suitable anti-biofilm actives. Biofilms containing Streptococcus gordonii, Fusobacterium nucleatum, Porphyromonas gingivalis, and Candida albicans were established from ontological analysis. Biofilms were optimized in different media and atmospheric conditions, prior to quantification and imaging, and subsequently treated with chlorhexidine, EDTA, and chitosan. These studies demonstrated that either media supplemented with serum were equally optimal for biofilm growth, which were dominated by S. gordonii, followed by C. albicans. Assessment of antimicrobial activity showed significant effectiveness of each antimicrobial, irrespective of serum. Chitosan was most effective (3 log reduction), and preferentially targeted C. albicans in both biofilm treatment and inhibition models. Chitosan was similarly effective at preventing biofilm growth on a dentine substrate. This study has shown that a reproducible and robust complex interkingdom model, which when tested with the antifungal chitosan, supports the notion of C. albicans as a key structural component. Full article
(This article belongs to the Special Issue Fungal and Polymicrobial Biofilms)
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15 pages, 2729 KiB  
Article
The Proteome of Community Living Candida albicans Is Differentially Modulated by the Morphologic and Structural Features of the Bacterial Cohabitants
by Thuyen Truong, Li Mei Pang, Suhasini Rajan, Sarah Sze Wah Wong, Yi Man Eva Fung, Lakshman Samaranayake and Chaminda Jayampath Seneviratne
Microorganisms 2020, 8(10), 1541; https://doi.org/10.3390/microorganisms8101541 - 7 Oct 2020
Cited by 2 | Viewed by 2338
Abstract
Candida albicans is a commensal polymorphic and opportunistic fungus, which usually resides as a small community in the oral cavities of a majority of humans. The latter eco-system presents this yeast varied opportunities for mutualistic interactions with other cohabitant oral bacteria, that synergizes [...] Read more.
Candida albicans is a commensal polymorphic and opportunistic fungus, which usually resides as a small community in the oral cavities of a majority of humans. The latter eco-system presents this yeast varied opportunities for mutualistic interactions with other cohabitant oral bacteria, that synergizes its persistence and pathogenicity. Collectively, these communities live within complex plaque biofilms which may adversely affect the oral health and increase the proclivity for oral candidiasis. The proteome of such oral biofilms with myriad interkingdom interactions are largely underexplored. Herein, we employed limma differential expression analysis, and cluster analysis to explore the proteomic interactions of C. albicans biofilms with nine different common oral bacterial species, Aggregatibacter actinomycetemcomitans, Actinomyces naeslundii, Fusobacterium nucleatum, Enterococcus faecalis, Porphyromonas gingivalis, Streptococcus mutants, Streptococcus sanguinis, Streptococcus mitis, and Streptococcus sobrinus. Interestingly, upon exposure of C. albicans biofilms to the foregoing heat-killed bacteria, the proteomes of the fungus associated with cellular respiration, translation, oxidoreductase activity, and ligase activity were significantly altered. Subsequent differential expression and cluster analysis revealed the subtle, yet significant alterations in the C. albicans proteome, particularly on exposure to bacteria with dissimilar cell morphologies, and Gram staining characteristics. Full article
(This article belongs to the Special Issue Fungal and Polymicrobial Biofilms)
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16 pages, 1436 KiB  
Article
A Selective Serotonin Reuptake Inhibitor, a Proton Pump Inhibitor, and Two Calcium Channel Blockers Inhibit Candida albicans Biofilms
by Clarissa J. Nobile, Craig L. Ennis, Nairi Hartooni, Alexander D. Johnson and Matthew B. Lohse
Microorganisms 2020, 8(5), 756; https://doi.org/10.3390/microorganisms8050756 - 18 May 2020
Cited by 9 | Viewed by 2934
Abstract
Biofilms formed by the human fungal pathogen Candida albicans are naturally resistant to many of the antifungal agents commonly used in the clinic. We screened a library containing 1600 clinically tested drug compounds to identify compounds that inhibit C. albicans biofilm formation. The [...] Read more.
Biofilms formed by the human fungal pathogen Candida albicans are naturally resistant to many of the antifungal agents commonly used in the clinic. We screened a library containing 1600 clinically tested drug compounds to identify compounds that inhibit C. albicans biofilm formation. The compounds that emerged from the initial screen were validated in a secondary screen and then tested for (1) their abilities to disrupt mature biofilms and (2) for synergistic interactions with representatives of the three antifungal agents most commonly prescribed to treat Candida infections, fluconazole, amphotericin B, and caspofungin. Twenty compounds had antibiofilm activity in at least one of the secondary assays and several affected biofilms but, at the same concentration, had little or no effect on planktonic (suspension) growth of C. albicans. Two calcium channel blockers, a selective serotonin reuptake inhibitor, and an azole-based proton pump inhibitor were among the hits, suggesting that members of these three classes of drugs or their derivatives may be useful for treating C. albicans biofilm infections. Full article
(This article belongs to the Special Issue Fungal and Polymicrobial Biofilms)
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Review

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23 pages, 805 KiB  
Review
Agent Based Models of Polymicrobial Biofilms and the Microbiome—A Review
by Sherli Koshy-Chenthittayil, Linda Archambault, Dhananjai Senthilkumar, Reinhard Laubenbacher, Pedro Mendes and Anna Dongari-Bagtzoglou
Microorganisms 2021, 9(2), 417; https://doi.org/10.3390/microorganisms9020417 - 17 Feb 2021
Cited by 11 | Viewed by 5693
Abstract
The human microbiome has been a focus of intense study in recent years. Most of the living organisms comprising the microbiome exist in the form of biofilms on mucosal surfaces lining our digestive, respiratory, and genito-urinary tracts. While health-associated microbiota contribute to digestion, [...] Read more.
The human microbiome has been a focus of intense study in recent years. Most of the living organisms comprising the microbiome exist in the form of biofilms on mucosal surfaces lining our digestive, respiratory, and genito-urinary tracts. While health-associated microbiota contribute to digestion, provide essential nutrients, and protect us from pathogens, disturbances due to illness or medical interventions contribute to infections, some that can be fatal. Myriad biological processes influence the make-up of the microbiota, for example: growth, division, death, and production of extracellular polymers (EPS), and metabolites. Inter-species interactions include competition, inhibition, and symbiosis. Computational models are becoming widely used to better understand these interactions. Agent-based modeling is a particularly useful computational approach to implement the various complex interactions in microbial communities when appropriately combined with an experimental approach. In these models, each cell is represented as an autonomous agent with its own set of rules, with different rules for each species. In this review, we will discuss innovations in agent-based modeling of biofilms and the microbiota in the past five years from the biological and mathematical perspectives and discuss how agent-based models can be further utilized to enhance our comprehension of the complex world of polymicrobial biofilms and the microbiome. Full article
(This article belongs to the Special Issue Fungal and Polymicrobial Biofilms)
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22 pages, 401 KiB  
Review
Microbial Interkingdom Biofilms and the Quest for Novel Therapeutic Strategies
by Katrien Van Dyck, Rita M. Pinto, Durgasruthi Pully and Patrick Van Dijck
Microorganisms 2021, 9(2), 412; https://doi.org/10.3390/microorganisms9020412 - 17 Feb 2021
Cited by 22 | Viewed by 3502
Abstract
Fungal and bacterial species interact with each other within polymicrobial biofilm communities in various niches of the human body. Interactions between these species can greatly affect human health and disease. Diseases caused by polymicrobial biofilms pose a major challenge in clinical settings because [...] Read more.
Fungal and bacterial species interact with each other within polymicrobial biofilm communities in various niches of the human body. Interactions between these species can greatly affect human health and disease. Diseases caused by polymicrobial biofilms pose a major challenge in clinical settings because of their enhanced virulence and increased drug tolerance. Therefore, different approaches are being explored to treat fungal–bacterial biofilm infections. This review focuses on the main mechanisms involved in polymicrobial drug tolerance and the implications of the polymicrobial nature for the therapeutic treatment by highlighting clinically relevant fungal–bacterial interactions. Furthermore, innovative treatment strategies which specifically target polymicrobial biofilms are discussed. Full article
(This article belongs to the Special Issue Fungal and Polymicrobial Biofilms)
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