The Interface between Fungal Biofilms and Innate Immunity

Kernien, John F.; Snarr, Brendan D.; Sheppard, Donald C.; Nett, Jeniel E.

doi:10.3389/fimmu.2017.01968

Cited by 104 publications

(68 citation statements)

References 145 publications

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“…Conventional and sexual biofilms also differ in their interactions with the host immune response. Neutrophils and mononuclear leukocytes are important host players against fungal infections [103,104]. When neutrophils recognize C. albicans cells, they activate a number of antimicrobial defenses, including phagocytosis, degranulation, the release of reactive oxygen species (ROS), and the release of web-like neutrophil extracellular traps (NETs) [103].…”

Section: Properties Of Conventional and Sexual Biofilms Comparedmentioning

confidence: 99%

“…Neutrophils and mononuclear leukocytes are important host players against fungal infections [103,104]. When neutrophils recognize C. albicans cells, they activate a number of antimicrobial defenses, including phagocytosis, degranulation, the release of reactive oxygen species (ROS), and the release of web-like neutrophil extracellular traps (NETs) [103]. In general, neutrophils are very effective at killing planktonic C. albicans yeast and hyphal cells [105], where these antimicrobial mechanisms work efficiently.…”

Section: Properties Of Conventional and Sexual Biofilms Comparedmentioning

confidence: 99%

“…In terms of mononuclear leukocytes, these host cells typically respond to C. albicans infection by phagocytosing invading cells and releasing cytokines [108]. C. albicans cells in conventional biofilms are two to three times more resistant to killing by mononuclear leukocytes than cells growing planktonically [103,108]. In addition, C. albicans cells growing in conventional biofilms are capable of altering the cytokine profile of attacking mononuclear cells [108].…”

Section: Properties Of Conventional and Sexual Biofilms Comparedmentioning

confidence: 99%

“…In addition, C. albicans cells growing in conventional biofilms are capable of altering the cytokine profile of attacking mononuclear cells [108]. For example, the presence of a conventional biofilm leads to the downregulation of TNF-α, a pro-inflammatory cytokine produced by mononuclear leukocytes that would normally suppress biofilm formation [103,108,109]. Intriguingly, conventional biofilms that are grown in the presence of mononuclear leukocytes form thicker biofilms, a phenomenon that is thought to be mediated by an unknown soluble factor that is present when the two are co-cultured [108].…”

Section: Properties Of Conventional and Sexual Biofilms Comparedmentioning

confidence: 99%

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Unraveling How Candida albicans Forms Sexual Biofilms

Perry

Hernday

Nobile

2020

JoF

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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.

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Section: Properties Of Conventional and Sexual Biofilms Comparedmentioning

confidence: 99%

Section: Properties Of Conventional and Sexual Biofilms Comparedmentioning

confidence: 99%

Section: Properties Of Conventional and Sexual Biofilms Comparedmentioning

confidence: 99%

Section: Properties Of Conventional and Sexual Biofilms Comparedmentioning

confidence: 99%

See 2 more Smart Citations

Unraveling How Candida albicans Forms Sexual Biofilms

Perry

Hernday

Nobile

2020

JoF

View full text Add to dashboard Cite

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“…Furthermore, when compared to planktonic phase fungal cells, biofilm infections have increased virulence, higher recurrence rates and are known to readily disperse, forming secondary infection sites (Uppuluri et al, 2010;Ramage et al, 2012;Nobile and Johnson, 2015;Del Pozo, 2018). In addition, these pathogenic structures have been shown to suppress immune responses, rendering the host's intrinsic defences ineffective (Xie et al, 2012;Kernien et al, 2017). Taken together, Candida biofilms are hard to eradicate and actively promote their survival, procreation and virulence.…”

Section: Introductionmentioning

confidence: 99%

Whole slide imaging is a high-throughput method to assessCandidabiofilm formation

Raas

Silva

Freitas

et al. 2020

Preprint

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Biofilm formation is a potent factor in the pathogenesis of Candida species. The development of new strategies that enable fast and entire visualization of Candida biofilms is necessary to better understand their structure and response to antifungals agents. Here, we applied, for the first time, whole slide imaging (WSI), a technique that generates wide-field, high-resolution "digital slides", to study biofilm formation of Candida species during normal growth and after treatment with antifungals. Three relevant biofilm-forming Candida species (C. albicans ATCC 10231, C. glabrata ATCC 2001, and C. tropicalis ATCC 750) were cultivated to grow on glass coverslips in the presence or not of fluconazole or nystatin. Accumulated biofilms on coverslips were then fixed, stained with fluorescent molecular markers for DNA and fungal wall (DAPI or calcofluor-white, respectively), and scanned in both bright-field and fluorescence mode using a digital scanner. WSI enabled clear observation of both size and morphological features of Candida biofilms. Quantitative analyses easily detected significant reduction in the surface area covered by biofilms when Candida species were exposed to antifungals compared to controls. When the proportions of the whole biofilm areas were compared by using different scanning modalities, there were no significant differences, indicating that the biofilm architecture can be adequately visualized in both bright-field and fluorescence modes and with different fluorophores. High-resolution WSI images also revealed structural aspects of biofilm-composed cells. Fungal cell shape and organization varied from round (isolated yeasts) to elongated cells and WSI morphometric analyses captured significant variations in cell area and cell roundness between Candida species. Parallel analyses using scanning electron microscopy confirmed the same observations obtained with WSI in terms of cell morphology, thus demonstrating that WSI resolution is accurate even at single-cell level. Taken together, WSI application allows reliable visualization of Candida biofilms from the whole architecture to morphological cell features. Thus, WSI can be a worthy addition to the available microscopic toolset to image and analyse fungal biofilms.3

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Galleria mellonella as an alternative in vivo model to study implant‐associated fungal infections

Mannala

Rupp

Walter

et al. 2023

Journal Orthopaedic Research

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Fungal implant‐associated bone infections are rare but difficult to treat and often associated with a poor outcome for patients. Candida species account for approximately 90% of all fungal infections. In vivo biofilm models play a major role to study biofilm development and potential new treatment options; however, there are only a very few in vivo models to study fungi‐associated biofilms. Furthermore, mammalian infection models are replaced more and more due to ethical restrictions with other alternative models in basic research. Recently, we developed an insect infection model with Galleria mellonella larvae to study biofilm‐associated infections with bacteria. Here, we further expanded the G. mellonella model to study in vivo fungal infections using Candida albicans and Candida krusei. We established a planktonic and biofilm‐implant model to test different antifungal medication with amphotericin B, fluconazole, and voriconazole against the two species and assessed the fungal biofilm‐load on the implant surface. Planktonic infection with C. albicans and C. krusei showed the killing of the G. mellonella larvae at 5 × 105 colony forming units (CFU). Treatment of larvae with antifungal compounds with amphotericin B and fluconazole showed significant survival improvement against planktonic C. albicans infection, but voriconazole had no effect. Titanium and stainless steel K‐wires were preincubated with C. albicans and implanted inside the larvae to induce biofilm infection on the implant surface. The survival analysis revealed significantly reduced survival of the larvae with Candida spp. infection compared to noninfected implants. The treatment with antifungal amphotericin B and fluconazole resulted in a slight and nonsignificant improvement survival of the larvae. The treatment with the antifungal compounds in the biofilm‐infection model was not as effective as in the planktonic infection model, which highlights the resistance of fungal biofilms to antifungal compounds like in bacterial biofilms. Scanning electron microscopy (SEM) analysis revealed the formation of a fungal biofilm with hyphae and spores associated with larvae tissue on the implant surface. Thus, our study highlights the use of G. mellonella larvae as alternative in vivo model to study biofilm‐associated implant fungal infections and that fungal biofilms exhibit high resistance profiles comparable to bacterial biofilms. The model can be used in the future to test antifungal treatment options for fungal biofilm infections.

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The Interface between Fungal Biofilms and Innate Immunity

Cited by 104 publications

References 145 publications

Unraveling How Candida albicans Forms Sexual Biofilms

Unraveling How Candida albicans Forms Sexual Biofilms

Whole slide imaging is a high-throughput method to assessCandidabiofilm formation

Galleria mellonella as an alternative in vivo model to study implant‐associated fungal infections

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