Proteomic Profile of <i>Cryptococcus neoformans</i> Biofilm Reveals Changes in Metabolic Processes

Santi, Lucélia; Beys‐da‐Silva, Walter O.; Berger, Markus; Calzolari, Diego; Guimarães, Jorge A.; Moresco, James J.; Yates, John R.

doi:10.1021/pr401075f

Cited by 65 publications

(63 citation statements)

References 85 publications

(167 reference statements)

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“…This wide-spread phenomenon termed the diauxic shift and is marked by the activation of the glyoxylate cycle (Zampar et al, 2013), and is under control of the cAMP repressor protein (Shimizu, 2013). Specific enzymes for this pathway have been shown to be upregulated in the stressed environment of biofilms in Cryptococcus neoformans (Santi et al, 2014). 6.…”

Section: Figmentioning

confidence: 99%

A Network Biology Approach to Decipher Stress Response in Bacteria UsingEscherichia coliAs a Model

Nagar

Aggarwal

Joon

et al. 2016

OMICS: A Journal of Integrative Biology

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The development of drug-resistant pathogenic bacteria poses challenges to global health for their treatment and control. In this context, stress response enables bacterial populations to survive extreme perturbations in the environment but remains poorly understood. Specific modules are activated for unique stressors with few recognized global regulators. The phenomenon of cross-stress protection strongly suggests the presence of central proteins that control the diverse stress responses. In this work, Escherichia coli was used to model the bacterial stress response. A Protein-Protein Interaction Network was generated by integrating differentially expressed genes in eight stress conditions of pH, temperature, and antibiotics with relevant gene ontology terms. Topological analysis identified 24 central proteins. The well-documented role of 16 central proteins in stress indicates central control of the response, while the remaining eight proteins may have a novel role in stress response. Cluster analysis of the generated network implicated RNA binding, flagellar assembly, ABC transporters, and DNA repair as important processes during response to stress. Pathway analysis showed crosstalk of Two Component Systems with metabolic processes, oxidative phosphorylation, and ABC transporters. The results were further validated by analysis of an independent cross-stress protection dataset. This study also reports on the ways in which bacterial stress response can progress to biofilm formation. In conclusion, we suggest that drug targets or pathways disrupting bacterial stress responses can potentially be exploited to combat antibiotic tolerance and multidrug resistance in the future.

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Section: Figmentioning

confidence: 99%

A Network Biology Approach to Decipher Stress Response in Bacteria UsingEscherichia coliAs a Model

Nagar

Aggarwal

Joon

et al. 2016

OMICS: A Journal of Integrative Biology

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“…The pattern of lactate is also interesting. We described here a mature (72 h old) biofilm, potentially marked by reduced levels of oxygen-a condition promoting anaerobic glycolysis and the inhibition of the TCA cycle [38]. With respect to Xcc, lactate was downregulated at comparable levels in both Xccϕ1, Xccϕ1+C20:0 and Xccϕ1+HA+C20:0 classes.…”

Section: Discussionmentioning

confidence: 98%

Bacteriophages Promote Metabolic Changes in Bacteria Biofilm

et al. 2020

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Bacterial biofilm provides bacteria with resistance and protection against conventional antimicrobial agents and the host immune system. Bacteriophages are known to move across the biofilm to make it permeable to antimicrobials. Mineral hydroxyapatite (HA) can improve the lytic activity of bacteriophages, and, together with eicosanoic acid (C20:0), can destroy the biofilm structure. Here, we demonstrate the efficacy of the combined use of phage, HA and C20:0 against Xanthomonas campestris pv campestris (Xcc) biofilm. We used nuclear magnetic resonance (NMR)-based metabolomics to investigate the molecular determinants related to the lytic action, aiming at identifying the metabolic pathways dysregulated by phage treatment. Furthermore, we identified specific markers (amino acids, lactate and galactomannan) which are involved in the control of biofilm stability. Our data show that Xccφ1, alone or in combination with HA and C20:0, interferes with the metabolic pathways involved in biofilm formation. The approach described here might be extended to other biofilm-producing bacteria.

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“…C. neoformans biofilms have been reported on medical devices (30, 31). 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).…”

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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Proteomic Profile of Cryptococcus neoformans Biofilm Reveals Changes in Metabolic Processes

Cited by 65 publications

References 85 publications

A Network Biology Approach to Decipher Stress Response in Bacteria UsingEscherichia coliAs a Model

A Network Biology Approach to Decipher Stress Response in Bacteria UsingEscherichia coliAs a Model

Bacteriophages Promote Metabolic Changes in Bacteria Biofilm

Variation in cell surface hydrophobicity amongCryptococcus neoformansstrains influences interactions with amoeba

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