The Crucial Role of Biofilms in Cryptococcus neoformans Survival within Macrophages and Colonization of the Central Nervous System

Aslanyan, Lilit; Sanchez, David A.; Valdebenito, Silvana; Eugenín, Eliseo A.; Ramos, Raddy L.; Martinez, Luis R.

doi:10.3390/jof3010010

Cited by 43 publications

(28 citation statements)

References 78 publications

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“…The self-produced polysaccharide rich extracellular polymeric matrix (EPM) of biofilm makes the sessile cryptococcal cells resistant to standard antimicrobial therapy resulting in fungal resistance. These biofilm-associated cryptococcal cells are also protected from macrophage phagocytosis in tissues thereby enhancing its quorum sensing and survival (Aslanyan et al, 2017 ). Some cases of C. neoformans and C. laurentii forming biofilm have been associated with the ventriculoatrial shunt, indwelling intravascular catheters, cardiac valve and peritoneal dialysis fistula (Ajesh and Sreejith, 2012 ; Martinez and Casadevall, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Antifungal and Anti-Biofilm Activity of Essential Oil Active Components against Cryptococcus neoformans and Cryptococcus laurentii

et al. 2017

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Cryptococcosis is an emerging and recalcitrant systemic infection occurring in immunocompromised patients. This invasive fungal infection is difficult to treat due to the ability of Cryptococcus neoformans and Cryptococcus laurentii to form biofilms resistant to standard antifungal treatment. The toxicity concern of these drugs has stimulated the search for natural therapeutic alternatives. Essential oil and their active components (EO-ACs) have shown to possess the variety of biological and pharmacological properties. In the present investigation the effect of six (EO-ACs) sourced from Oregano oil (Carvacrol), Cinnamon oil (Cinnamaldehyde), Lemongrass oil (Citral), Clove oil (Eugenol), Peppermint oil (Menthol) and Thyme oil (thymol) against three infectious forms; planktonic cells, biofilm formation and preformed biofilm of C. neoformans and C. laurentii were evaluated as compared to standard drugs. Data showed that antibiofilm activity of the tested EO-ACs were in the order: thymol>carvacrol>citral>eugenol=cinnamaldehyde>menthol respectively. The three most potent EO-ACs, thymol, carvacrol, and citral showed excellent antibiofilm activity at a much lower concentration against C. laurentii in comparison to C. neoformans indicating the resistant nature of the latter. Effect of the potent EO-ACs on the biofilm morphology was visualized using scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM), which revealed the absence of extracellular polymeric matrix (EPM), reduction in cellular density and alteration in the surface morphology of biofilm cells. Further, to realize the efficacy of the EO-ACs in terms of human safety, cytotoxicity assays and co-culture model were evaluated. Thymol and carvacrol as compared to citral were the most efficient in terms of human safety in keratinocyte- Cryptococcus sp. co-culture infection model suggesting that these two can be further exploited as cost-effective and non-toxic anti-cryptococcal drugs.

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Section: Introductionmentioning

confidence: 99%

Antifungal and Anti-Biofilm Activity of Essential Oil Active Components against Cryptococcus neoformans and Cryptococcus laurentii

et al. 2017

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“…Biofilm associated cells have been associated with increased tolerance against antifungal drugs and phagocytic cells, as they upregulate proteins associated with host defense (32–34). In-vivo, C. neoformans form biofilm-like structures called cryptococcomas that could play a role in its neurotropism (35). The surface property of cells may affect the aggregation of microbial communities in biofilms.…”

Section: Discussionmentioning

confidence: 99%

Variation in cell surface hydrophobicity amongCryptococcus neoformansstrains influences interactions with amoeba

Vij

Crawford

Casadevall

2019

Preprint

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ABSTRACTCryptococcus neoformans and Cryptococcus gattii are pathogenic fungi that cause significant morbidity and mortality. Cell surface hydrophobicity (CSH) is a biophysical parameter that influences the adhesion of fungal cells or spores to biotic and abiotic surfaces. C. neoformans is encased by polysaccharide capsule that is highly hydrophilic and is a critical determinant of virulence. In this study, we report large differences in the CSH of some C. neoformans and C. gattii strains. The capsular polysaccharides of C. neoformans strains differ in repeating motifs, and therefore vary in the number of hydroxyl groups, which along with higher-order structure of the capsule, may contribute to the variation in hydrophobicity that we observed. For C. neoformans, CSH correlated with phagocytosis by natural soil predator Acanthamoeba castellani. Furthermore, capsular binding of the protective antibody (18B7), but not the non-protective (13F1) antibody altered the CSH of C. neoformans strains. Variability in CSH could be an important characteristic when comparing the biological properties of cryptococcal strains.IMPORTANCEThe interaction of a microbial cell with its environment is influenced by the biophysical properties of a cell. The affinity of the cell surface for water, defined by the Cell Surface Hydrophobicity (CSH), is a biophysical parameter that varied amongst different strains of Cryptococcus neoformans. The CSH influenced the phagocytosis of the yeast by its natural predator in the soil, Amoeba. Studying variation in biophysical properties like CSH gives us insight into the dynamic host-predator interaction, and host-pathogen interaction in a damage-response framework.

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“…C. neoformans biofilm-like structures known as cryptococcomas play a crucial role for the successful colonization of the host central nervous system (CNS) (reviewed by [ 120 ]). Following invasion of the brain parenchyma, the biofilm-like adaptation is favored by slowed proliferation due to cell cycle regulation (G2-arrest) [ 121 ], reduced protein synthesis and energy acquisition from a fermentation pathway rather than the tricarboxylic acid cycle [ 54 ], which allows fungal survival under oxygen-limited conditions.…”

Section: Cryptococcal Adhesion Toolsmentioning

confidence: 99%

Cryptococcal Traits Mediating Adherence to Biotic and Abiotic Surfaces

Camacho

Casadevall

2018

JoF

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Several species in the genus Cryptococcus are facultative intracellular pathogens capable of causing disease associated with high mortality and morbidity in humans. These fungi interact with other organisms in the soil, and these interactions may contribute to the development of adaptation mechanisms that function in virulence by promoting fungal survival in animal hosts. Fungal adhesion molecules, also known as adhesins, have been classically considered as cell-surface or secreted proteins that play critical roles in microbial pathogenesis or in biofilm formation as structural components. Pathogenic Cryptococcus spp. differ from other pathogenic yeasts in having a polysaccharide capsule that covers the cell wall surface and precludes interactions of those structures with host cell receptors. Hence, pathogenic Cryptococcus spp. use unconventional tools for surface attachment. In this essay, we review the unique traits and mechanisms favoring adhesion of Cryptococcus spp. to biotic and abiotic surfaces. Knowledge of the traits that mediate adherence could be exploited in the development of therapeutic, biomedical, and/or industrial products.

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The Crucial Role of Biofilms in Cryptococcus neoformans Survival within Macrophages and Colonization of the Central Nervous System

Cited by 43 publications

References 78 publications

Antifungal and Anti-Biofilm Activity of Essential Oil Active Components against Cryptococcus neoformans and Cryptococcus laurentii

Antifungal and Anti-Biofilm Activity of Essential Oil Active Components against Cryptococcus neoformans and Cryptococcus laurentii

Variation in cell surface hydrophobicity amongCryptococcus neoformansstrains influences interactions with amoeba

Cryptococcal Traits Mediating Adherence to Biotic and Abiotic Surfaces

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