Strength in numbers: antifungal strategies against fungal biofilms

Ramage, Gordon; Robertson, Shaun N.; Williams, Craig

doi:10.1016/j.ijantimicag.2013.10.023

Cited by 79 publications

(47 citation statements)

References 142 publications

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“…Candidiasis has become increasingly recognized as having a biofilm etiology (21,29). Recent studies have shown that there is a positive correlation between biofilm-forming ability and poor clinical outcomes (30), which is inextricably linked to C. albicans filamentation (31).…”

Section: Discussionmentioning

confidence: 99%

Acetylcholine Protects against Candida albicans Infection by Inhibiting Biofilm Formation and Promoting Hemocyte Function in a Galleria mellonella Infection Model

et al. 2015

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dBoth neuronal acetylcholine and nonneuronal acetylcholine have been demonstrated to modulate inflammatory responses. Studies investigating the role of acetylcholine in the pathogenesis of bacterial infections have revealed contradictory findings with regard to disease outcome. At present, the role of acetylcholine in the pathogenesis of fungal infections is unknown. Therefore, the aim of this study was to determine whether acetylcholine plays a role in fungal biofilm formation and the pathogenesis of Candida albicans infection. The effect of acetylcholine on C. albicans biofilm formation and metabolism in vitro was assessed using a crystal violet assay and phenotypic microarray analysis. Its effect on the outcome of a C. albicans infection, fungal burden, and biofilm formation were investigated in vivo using a Galleria mellonella infection model. In addition, its effect on modulation of host immunity to C. albicans infection was also determined in vivo using hemocyte counts, cytospin analysis, larval histology, lysozyme assays, hemolytic assays, and real-time PCR. Acetylcholine was shown to have the ability to inhibit C. albicans biofilm formation in vitro and in vivo. In addition, acetylcholine protected G. mellonella larvae from C. albicans infection mortality. The in vivo protection occurred through acetylcholine enhancing the function of hemocytes while at the same time inhibiting C. albicans biofilm formation. Furthermore, acetylcholine also inhibited inflammation-induced damage to internal organs. This is the first demonstration of a role for acetylcholine in protection against fungal infections, in addition to being the first report that this molecule can inhibit C. albicans biofilm formation. Therefore, acetylcholine has the capacity to modulate complex host-fungal interactions and plays a role in dictating the pathogenesis of fungal infections.

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Section: Discussionmentioning

confidence: 99%

Acetylcholine Protects against Candida albicans Infection by Inhibiting Biofilm Formation and Promoting Hemocyte Function in a Galleria mellonella Infection Model

et al. 2015

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“…This review does not cover in detail the literature on the signal transduction pathways that regulate gene expression during biofilm formation, the genes that are differentially regulated, or the molecular mechanisms regulating matrix formation or drug resistance, unless that information pertains to the specific aim set forth. The reader is directed to a number of excellent reviews on these subjects, published in the past several years (47)(48)(49)(50)(51)(52)(53)(54)(55).…”

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Plasticity of Candida albicans Biofilms

Soll

Daniels

2016

Microbiol Mol Biol Rev

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SUMMARYCandida albicans, the most pervasive fungal pathogen that colonizes humans, forms biofilms that are architecturally complex. They consist of a basal yeast cell polylayer and an upper region of hyphae encapsulated in extracellular matrix. However, biofilms formedin vitrovary as a result of the different conditions employed in models, the methods used to assess biofilm formation, strain differences, and, in a most dramatic fashion, the configuration of the mating type locus (MTL). Therefore, integrating data from different studies can lead to problems of interpretation if such variability is not taken into account. Here we review the conditions and factors that cause biofilm variation, with the goal of engendering awareness that more attention must be paid to the strains employed, the methods used to assess biofilm development, every aspect of the model employed, and the configuration of theMTLlocus. We end by posing a set of questions that may be asked in comparing the results of different studies and developing protocols for new ones. This review should engender the notion that not all biofilms are created equal.

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“…Infection arises when the yeast is able to overcome the host immune response, and this interplay is regulated by pro-and anti-inflammatory mediators. The extracellular carbohydrate matrix of biofilms provides a very distinctive and protective niche in which yeast cells can grow within the host, and the cells often show an altered phenotype and antifungal resistance profile compared to those of planktonic counterparts (6,7). The cells embedded within biofilms are able to evade host immune cells since the cell surface structures are masked (1).…”

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dl-2-Hydroxyisocaproic Acid Attenuates Inflammatory Responses in a Murine Candida albicans Biofilm Model

Nieminen¹,

Hernández²,

Frazer³

et al. 2014

Clin. Vaccine Immunol.

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f Chronic biofilm infections are often accompanied by a chronic inflammatory response, leading to impaired healing and increased, irreversible damage to host tissues. Biofilm formation is a major virulence factor for Candida albicans and a challenge for treatment. Most current antifungals have proved ineffective in eradicating infections attributed to biofilms. The biofilm structure protects Candida species against antifungals and provides a way for them to evade host immune systems. This leads to a very distinct inflammatory response compared to that seen in planktonic infections. Previously, we showed the superior efficacy of DL-2-hydroxyisocaproic acid (HICA) against various bacteria and fungi. However, the immunomodulatory properties of HICA have not been studied. Our aim was to investigate the potential anti-inflammatory response to HICA in vivo. We hypothesized that HICA reduces the levels of immune mediators and attenuates the inflammatory response. In a murine model, a robust biofilm was formed for 5 days in a diffusion chamber implanted underneath mouse skin. The biofilm was treated for 12 h with HICA, while caspofungin and phosphate-buffered saline (PBS) were used as controls. The pathophysiology and immunoexpression in the tissues surrounding the chamber were determined by immunohistochemistry. Histopathological examination showed an attenuated inflammatory response together with reduced expression of matrix metalloproteinase 9 (MMP-9) and myeloperoxidase (MPO) compared to those of chambers containing caspofungin and PBS. Interestingly, the expression of developmental endothelial locus 1 (Del-1), an antagonist of neutrophil extravasation, increased after treatment with HICA. Considering its anti-inflammatory and antimicrobial activity, HICA may have enormous therapeutic potential in the treatment of chronic biofilm infections and inflammation, such as those seen with chronic wounds.

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Strength in numbers: antifungal strategies against fungal biofilms

Cited by 79 publications

References 142 publications

Acetylcholine Protects against Candida albicans Infection by Inhibiting Biofilm Formation and Promoting Hemocyte Function in a Galleria mellonella Infection Model

Acetylcholine Protects against Candida albicans Infection by Inhibiting Biofilm Formation and Promoting Hemocyte Function in a Galleria mellonella Infection Model

Plasticity of Candida albicans Biofilms

dl-2-Hydroxyisocaproic Acid Attenuates Inflammatory Responses in a Murine Candida albicans Biofilm Model

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