The still obscure attributes of cryptococcal glucuronoxylomannan

Rodrigues, Márcio L.; Fonseca, Fernanda L.; Frasés, Susana; Casadevall, Arturo; Nimrichter, Leonardo

doi:10.3109/13693780902788621

Cited by 18 publications

(15 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The capsular size is unquestionably important for cryptococcal pathogenicity (28), but other biological and physical chemical properties of capsular components have also been linked to the mechanisms by which C. neoformans interacts with the host (52). Therefore, we evaluated the relevance of APT1 to general properties of extracellular polysaccharides and capsular components of C. neoformans.…”

Section: Deletion Of Atp1 Does Not Affect Global Flippase Activity In Cmentioning

confidence: 99%

Role of the Apt1 Protein in Polysaccharide Secretion by Cryptococcus neoformans

et al. 2014

Self Cite

View full text Add to dashboard Cite

e Flippases are key regulators of membrane asymmetry and secretory mechanisms. Vesicular polysaccharide secretion is essential for the pathogenic mechanisms of Cryptococcus neoformans. On the basis of the observations that flippases are required for polysaccharide secretion in plants and the putative Apt1 flippase is required for cryptococcal virulence, we analyzed the role of this enzyme in polysaccharide release by C. neoformans, using a previously characterized apt1⌬ mutant. Mutant and wild-type (WT) cells shared important phenotypic characteristics, including capsule morphology and dimensions, glucuronoxylomannan (GXM) composition, molecular size, and serological properties. The apt1⌬ mutant, however, produced extracellular vesicles (EVs) with a lower GXM content and different size distribution in comparison with those of WT cells. Our data also suggested a defective intracellular GXM synthesis in mutant cells, in addition to changes in the architecture of the Golgi apparatus. These findings were correlated with diminished GXM production during in vitro growth, macrophage infection, and lung colonization. This phenotype was associated with decreased survival of the mutant in the lungs of infected mice, reduced induction of interleukin-6 (IL-6) cytokine levels, and inefficacy in colonization of the brain. Taken together, our results indicate that the lack of APT1 caused defects in both GXM synthesis and vesicular export to the extracellular milieu by C. neoformans via processes that are apparently related to the pathogenic mechanisms used by this fungus during animal infection.

show abstract

Section: Deletion Of Atp1 Does Not Affect Global Flippase Activity In Cmentioning

confidence: 99%

Role of the Apt1 Protein in Polysaccharide Secretion by Cryptococcus neoformans

et al. 2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…vivo (150). Karashima and collaborators reported that T. asahii isolates could switch phenotype and increase the amount of secreted GXM after passage in a mouse model (91).…”

Section: Cell Wall Componentsmentioning

confidence: 99%

Current Knowledge of Trichosporon spp. and Trichosporonosis

2011

View full text Add to dashboard Cite

SUMMARY Trichosporon spp. are basidiomycetous yeast-like fungi found widely in nature. Clinical isolates are generally related to superficial infections. However, this fungus has been recognized as an opportunistic agent of invasive infections, mostly in cancer patients and those exposed to invasive medical procedures. It is possible that the ability of Trichosporon strains to form biofilms on implanted devices, the presence of glucuronoxylomannan in their cell walls, and the ability to produce proteases and lipases are all factors likely related to the virulence of this genus and therefore may account for the progress of invasive trichosporonosis. Disseminated trichosporonosis has been increasingly reported worldwide and represents a challenge for both diagnosis and species identification. Phenotypic identification methods are useful for Trichosporon sp. screening, but only molecular methods, such as IGS region sequencing, allow the complete identification of Trichosporon isolates at the species level. Methods for the diagnosis of invasive trichosporonosis include PCR-based methods, Luminex xMAP technology, and, more recently, proteomics. Treating patients with trichosporonosis remains a challenge because of limited data on the in vitro and in vivo activities of antifungal drugs against clinically relevant species of the genus. Despite the mentioned limitations, the use of antifungal regimens containing triazoles appears to be the best therapeutic approach.

show abstract

“…25,51 The MICs of the echinocandins and azoles corresponded to prominent growth inhibition (approximately 50% inhibition relative to control growth) or a complete growth inhibition in the case of amphotericin B. All the strains were also tested using the E-test susceptibility method, according to the manufacturer's instructions for VRC, PSC, ITZ, FLC, AMB and CFG (bioMerieux SA, 532800, 532100, 525808, 510800, 526300, 532400).…”

Section: In Vitro Susceptibility Testingmentioning

confidence: 99%

“…2,22 It has been speculated that the secretion of proteases and phospholipases are important virulence factors for scavenging nutrient inside the host. 23 These pathogens are also able to produce glucuronoxylomannan (GXM) in their cell walls, similarly to Cryptococcus neoformans 24,25 and it is possible this polysaccharide may help to attenuate phagocytosis by host immune cells. 25 However, there is no genetic evidence about the functionality of these virulence factors.…”

Section: Introductionmentioning

confidence: 99%

The development of animal infection models and antifungal efficacy assays against clinical isolates ofTrichosporon asahii,T. asteroidesandT. inkin

et al. 2015

View full text Add to dashboard Cite

The present study developed Galleria mellonella and murine infection models for the study of Trichosporon infections. The utility of the developed animal models was demonstrated through the assessment of virulence and antifungal efficacy for 7 clinical isolates of Trichosporon asahii, T. asteroides and T. inkin. The susceptibility of the Trichosporon isolates to several common antifungal drugs was tested in vitro using the broth microdilution and the Etest methods. The E-test method depicted a lower minimal inhibitory concentration (MIC) for amphotericin and a slightly higher MIC for caspofungin, while MICs observed for the azoles were different but comparable between both methods. All three Trichosporon species established infection in both the G. mellonella and immunosuppressed murine models. Species and strain dependent differences were observed in both the G. mellonella and murine models. T. asahii was demonstrated to be more virulent than the other 2 species in both animal hosts. Significant differences in virulence were observed between strains for T. asteroides in the murine model. In both animal models, fluconazole and voriconazole were able to improve the survival of the animals compared to the untreated control groups infected with any of the 3 Trichosporon species. In G. mellonella, amphotericin was not able to reduce mortality in any of the 3 species. In contrast, amphotericin was able to reduce murine mortality in the T. asahii or T. inkin models, respectively. Hence, the developed animal infection models can be directly applicable to the future deeper investigation of the molecular determinants of Trichosporon virulence and antifungal resistance.

show abstract

The still obscure attributes of cryptococcal glucuronoxylomannan

Cited by 18 publications

References 45 publications

Role of the Apt1 Protein in Polysaccharide Secretion by Cryptococcus neoformans

Role of the Apt1 Protein in Polysaccharide Secretion by Cryptococcus neoformans

Current Knowledge of Trichosporon spp. and Trichosporonosis

The development of animal infection models and antifungal efficacy assays against clinical isolates ofTrichosporon asahii,T. asteroidesandT. inkin

Contact Info

Product

Resources

About