Cryptococcus neoformans Host Adaptation: Toward Biological Evidence of Dormancy

Alanio, Alexandre; Vernel-Pauillac, Frédérique; Sturny-Leclère, Aude; Dromer, Françoise

doi:10.1128/mbio.02580-14

Cited by 109 publications

(132 citation statements)

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“…In vivo C. neoformans cells vary in size, from cells less than 3 µm in cell body diameter to cells more than 100 µm in diameter (Feldmesser et al, 2001; Okagaki et al, 2010; Zaragoza et al, 2010; Alanio et al, 2015). The in vivo C. neoformans cells were divided into two groups; typical cells (less than 10 µm of cell body diameter), and titan cells greater than 10 µm in cell body diameter.…”

Section: Resultsmentioning

confidence: 99%

“…During infection, C. neoformans cells of varying cell body size and capsule size are observed (Feldmesser et al, 2001; Okagaki et al, 2010; Zaragoza et al, 2010; Alanio et al, 2015). These structural and morphological characteristics allow C. neoformans to evade and modulate the host immune system (Almeida et al, 2001; Okagaki and Nielsen 2012; Wiesner et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

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Titan cell production in Cryptococcus neoformans reshapes the cell wall and capsule composition during infection

et al. 2018

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Cryptococcus neoformans is a human fungal pathogen that often causes infections in immunocompromised individuals. Upon inhalation into the lungs C. neoformans differentiates into cells with altered size and morphology, including production of large titan cells. Titan cells possess thickened cell wall and dense, cross-linked capsule when compared to in vitro grown cells. In addition, titan cells have increased cell wall chitin that is associated with a detrimental anti-inflammatory immune response. Here we examined the cell wall and capsule composition of in vitro, in vivo typical-sized and in vivo titan cells using High Performance Liquid Chromatography (HPLC). The monomer composition of cell wall polysaccharides showed that in vivo C. neoformans cells contained more glucosamine and less glucose than in vitro cells, suggesting alteration in abundance of both chitin and glucans, respectively. Low levels of galactosamine were also detected in carbohydrates from both in vivo and vitro cells. Within the in vivo cell population, differences in the proportions of cell wall and capsule monomers between typical and titan cells were also observed. Taken together, these results demonstrate that C. neoformans reshapes its cell wall and capsule composition during infection. These cell wall and capsule alterations likely help C. neoformans escape recognition by, and allow modulation of, the host immune system.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Titan cell production in Cryptococcus neoformans reshapes the cell wall and capsule composition during infection

et al. 2018

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“…Common methods of in vivo dissemination analysis of C. neoformans to study their pathogenesis within a host involve labeling them with fluorescent dyes such as fluorescein isothiocyanate (FITC) (Shi et al, 2010), Uvitex-2B (Nicola et al, 2012), (Davis et al, 2015) or 5-chloromethylfluorescein diacetate (CMFDA; (Alanio et al, 2015; Nicola et al, 2011). Although these studies have helped characterize important in vivo relationships that C. neoformans has with host cells, labeling C. neoformans with dyes to gain an understanding of their dissemination strategies, is cell-division limited.…”

Section: Discussionmentioning

confidence: 99%

A fluorogenic C. neoformans reporter strain with a robust expression of m-cherry expressed from a safe haven site in the genome

Upadhya

Lam

Maybruck

et al. 2017

Fungal Genetics and Biology

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C. neoformans is an encapsulated fungal pathogen with defined asexual and sexual life cycles. Due to the availability of genetic and molecular tools for its manipulation, it has become a model organism for studies of fungal pathogens, even though it lacks a reliable system for maintaining DNA fragments as extrachromosomal plasmids. To compensate for this deficiency, we identified a genomic gene-free intergenic region where heterologous DNA could be inserted by homologous recombination without adverse effects on the phenotype of the recipient strain. Since such a site in the C. neoformans genome at a different location has been named previously as “safe haven”, we named this locus second safe haven site (SH2). Insertion of DNA into this site in the genome of the KN99 congenic strain pair caused minimal change in the growth of the engineered strain under a variety of in vitro and in vivo conditions. We exploited this ‘safe’ locus to create a genetically stable highly fluorescent strain expressing mCherry protein (KN99mCH); this strain closely resembled its wild-type parent (KN99α) in growth under a variety of in vitro stress conditions and in the expression of virulence traits. The efficiency of phagocytosis and the proliferation of KN99mCH inside human monocyte-derived macrophages were comparable to those of KN99α, and the engineered strain showed the expected organ dissemination after inoculation, although there was a slight reduction in virulence. The mCherry fluorescence allowed us to measure specific association of cryptococci with leukocytes in the lungs and mediastinal lymph nodes of infected animals and, for the first-time, to assess their live/dead status in vivo. These results highlight the utility of KN99mCH for elucidation of host-pathogen interactions in vivo. Finally, we generated drug-resistant KN99 strains of both mating types that are marked at the SH2 locus with a specific drug resistant gene cassette; these strains will facilitate the generation of mutant strains by mating.

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“…Each of these components may have an effect on the host immune system [134,148,149]. The capsule protects cells from phagocytic activity by macrophages and neutrophils, and interferes with normal T cell function [150,151].…”

Section: Cryptococcosismentioning

confidence: 99%

Update on Fungal Disease: From Establish Infection to Clinical Manifestation

Melo¹,

Scorzoni²,

Rossi³

et al. 2017

J Biotechnol Biomater

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Fungal diseases have emerged as an important cause of morbidity and mortality, especially among immunocompromised patients. Pathogenic fungi have evolved an array of virulence factors to survive within the host and to outwit immune defenses. Fungi may cause a wide range of diseases in humans that range in extent from superficial to disseminated infections. Generally, the site of infections classifies the type of fungal disease, which can be divided into superficial, cutaneous, subcutaneous and systemic. In addition, the fungal virulence factors determine whether the infection will become established in the host. A primary pathogen may infect an immunologically normal host, whereas, an opportunistic pathogen requires some compromise of the host immune defenses in order for the infection to become established. This article covers the main fungi that are responsible for the increase of the fungal infections.Keywords: Fungal infections; Virulence; Yeast; Opportunistic infections; Endemic mycosis Fungal InfectionsFungal diseases have changed constantly in the last years. The virulence of these microorganisms has been adapted according to the human host, promoting a range of clinical manifestation. Several are the ways by which fungi promote a disease depending on human body part involved by the microorganism and the immunologic system of the host [1].In this review, we discuss the main fungal pathogens responsible for causing several diseases, highlighting on their virulence associate to clinical manifestation and the difficulty to accomplish the treatment. Superficial and cutaneous fungal diseasesSuperficial and cutaneous fungal infections are very common and occur worldwide affecting millions of people, especially immunocompromised patients. The most common types of these infections are dermatophytosis (tinea or ringworm), pityriasis versicolor (formerly tinea versicolor) and candidiasis (moniliasis). These occur by fungal invasion into the skin, keratinized tissues and mucous membranes [2]. Trichosporon and Fusarium species also cause superficial fungal infection, but also may be considered an invasive pathogen that may cause a systemic infection [3,4].Dermatophytosis: Dermatophytes are fungi that invade keratinized structures of humans and animals producing a condition called dermatophytosis or, more commonly, tinea [5,6]. These fungi belong to three main genera Trichophyton, Microsporum and Epidermophyton, of these T. rubrum is the most prevalent species worldwide [7,8]. The mechanisms of pathogenicity of these fungi are not yet well understood. There are several studies focusing on keratinolytic proteases (keratinases) produced by dermatophytes, but it is not known how these fungi regulate the use of these proteases to obtain nutrients from the stratum corneum substrate they invade, and whether there are additional roles of these proteins in adhesion and immunomodulation [9].To establish the infection, the contact of arthroconidia or hyphal fragmens with the host skin is essential. The fungi express spe...

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Cryptococcus neoformans Host Adaptation: Toward Biological Evidence of Dormancy

Cited by 109 publications

References 77 publications

Titan cell production in Cryptococcus neoformans reshapes the cell wall and capsule composition during infection

Titan cell production in Cryptococcus neoformans reshapes the cell wall and capsule composition during infection

A fluorogenic C. neoformans reporter strain with a robust expression of m-cherry expressed from a safe haven site in the genome

Update on Fungal Disease: From Establish Infection to Clinical Manifestation

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