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11 pages, 966 KiB

Open AccessArticle

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 2203

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

Open AccessArticle

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 17 | Viewed by 4255

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

Open AccessArticle

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 33 | Viewed by 5382

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

Open AccessArticle

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 3982

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

Open AccessArticle

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 3322

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

Open AccessArticle

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 1 | Viewed by 2246

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

Open AccessArticle

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 2855

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

Open AccessReview

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 5500

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

Open AccessReview

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 3382

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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