scholarly journals Degradation of human kininogens with the release of kinin peptides by extracellular proteinases of Candida spp.

2010 ◽  
Vol 391 (7) ◽  
Author(s):  
Maria Rapala-Kozik ◽  
Justyna Karkowska-Kuleta ◽  
Agnieszka Ryzanowska ◽  
Anna Golda ◽  
Anna Barbasz ◽  
...  

AbstractThe secretion of proteolytic enzymes by pathogenic microorganisms is one of the most successful strategies used by pathogens to colonize and infect the host organism. The extracellular microbial proteinases can seriously deregulate the homeostatic proteolytic cascades of the host, including the kinin-forming system, repeatedly reported to be activated during bacterial infection. The current study assigns a kinin-releasing activity to secreted proteinases ofCandidaspp. yeasts, the major fungal pathogens of humans. Of severalCandidaspecies studied,C. parapsilosisandC. albicansin their invasive filamentous forms are shown to produce proteinases which most effectively degrade proteinaceous kinin precursors, the kininogens. These enzymes, classified as aspartyl proteinases, have the highest kininogen-degrading activity at low pH (approx. 3.5), but the associated production of bradykinin-related peptides from a small fraction of kininogen molecules is optimal at neutral pH (6.5). The peptides effectively interact with cellular B2-type kinin receptors. Moreover, kinin-related peptides capable of interacting with inflammation-induced B1-type receptors are also formed, but with a reversed pH dependence. The presented variability of the potential extracellular kinin production by secreted aspartyl proteinases ofCandidaspp. is consistent with the known adaptability of these opportunistic pathogens to different niches in the host organism.

2021 ◽  
Vol 9 (7) ◽  
pp. 1405
Author(s):  
Raffaella Diotti ◽  
Michelle Esposito ◽  
Chang Hui Shen

Telomeres are long non-coding regions found at the ends of eukaryotic linear chromosomes. Although they have traditionally been associated with the protection of linear DNA ends to avoid gene losses during each round of DNA replication, recent studies have demonstrated that the role of these sequences and their adjacent regions go beyond just protecting chromosomal ends. Regions nearby to telomeric sequences have now been identified as having increased variability in the form of duplications and rearrangements that result in new functional abilities and biodiversity. Furthermore, unique fungal telomeric and chromatin structures have now extended clinical capabilities and understanding of pathogenicity levels. In this review, telomere structure, as well as functional implications, will be examined in opportunistic fungal pathogens, including Aspergillus fumigatus, Candida albicans, Candida glabrata, and Pneumocystis jirovecii.


2021 ◽  
Vol 22 (14) ◽  
pp. 7715
Author(s):  
Grzegorz Czernel ◽  
Dominika Bloch ◽  
Arkadiusz Matwijczuk ◽  
Jolanta Cieśla ◽  
Monika Kędzierska-Matysek ◽  
...  

Silver nanoparticles (AgNPs) were synthesized using aqueous honey solutions with a concentration of 2%, 10%, and 20%—AgNPs-H2, AgNPs-H10, and AgNPs-H20. The reaction was conducted at 35 °C and 70 °C. Additionally, nanoparticles obtained with the citrate method (AgNPs-C), while amphotericin B (AmB) and fluconazole were used as controls. The presence and physicochemical properties of AgNPs was affirmed by analyzing the sample with ultraviolet–visible (UV–Vis) and fluorescence spectroscopy, scanning electron microscopy (SEM), and dynamic light scattering (DLS). The 20% honey solution caused an inhibition of the synthesis of nanoparticles at 35 °C. The antifungal activity of the AgNPs was evaluated using opportunistic human fungal pathogens Candida albicans and Candida parapsilosis. The antifungal effect was determined by the minimum inhibitory concentration (MIC) and disc diffusion assay. The highest activity in the MIC tests was observed in the AgNPs-H2 variant. AgNPs-H10 and AgNPs-H20 showed no activity or even stimulated fungal growth. The results of the Kirby–Bauer disc diffusion susceptibility test for C. parapsilosis strains indicated stronger antifungal activity of AgNPs-H than fluconazole. The study demonstrated that the antifungal activity of AgNPs is closely related to the concentration of honey used for the synthesis thereof.


2021 ◽  
Vol 7 (2) ◽  
pp. 124
Author(s):  
Charmaine Retanal ◽  
Brianna Ball ◽  
Jennifer Geddes-McAlister

Post-translational modifications (PTMs) change the structure and function of proteins and regulate a diverse array of biological processes. Fungal pathogens rely on PTMs to modulate protein production and activity during infection, manipulate the host response, and ultimately, promote fungal survival. Given the high mortality rates of fungal infections on a global scale, along with the emergence of antifungal-resistant species, identifying new treatment options is critical. In this review, we focus on the role of PTMs (e.g., phosphorylation, acetylation, ubiquitination, glycosylation, and methylation) among the highly prevalent and medically relevant fungal pathogens, Candida spp., Aspergillus spp., and Cryptococcus spp. We explore the role of PTMs in fungal stress response and host adaptation, the use of PTMs to manipulate host cells and the immune system upon fungal invasion, and the importance of PTMs in conferring antifungal resistance. We also provide a critical view on the current knowledgebase, pose questions key to our understanding of the intricate roles of PTMs within fungal pathogens, and provide research opportunities to uncover new therapeutic strategies.


2021 ◽  
Author(s):  
Si Jie Lim ◽  
Mohd Shukuri Mohamad Ali ◽  
Suriana Sabri ◽  
Noor Dina Muhd Noor ◽  
Abu Bakar Salleh ◽  
...  

Abstract Candidiasis is a fungal infection caused by Candida spp. especially Candida albicans, C. glabrata, C. parapsilosis and C. tropicalis. Although the medicinal therapeutic strategies have rapidly improved, the mortality rate due to candidiasis has continuously increased. The secreted and membrane-bound virulence factors (VFs) are responsible for fungal invasion, damage and translocation through the host enterocytes besides the evasion from host immune system. VFs such as agglutinin-like sequences (Als), heat shock protein 70, phospholipases, secreted aspartyl proteinases (Sap), lipases, enolases and phytases are mostly hydrolases which degrade the enterocyte membrane components except for candidalysin, the VF acts as a peptide toxin to induce necrotic cell lysis. To date, structural studies of the VFs remain underexplored, hindering their functional analyses. Among the VFs, only secreted aspartyl proteinases and agglutinin-like sequences have their structures deposited in Protein Data Bank (PDB). Therefore, this review scrutinizes the mechanisms of these VFs by discussing the VF-deficient studies of several Candida spp. and their abilities to produce these VFs. Nonetheless, their latest reported sequential and structural analyses are discussed to impart a wider perception of the host-pathogen interactions and potential vaccine or antifungal drug targets. This review signifies that more VFs structural investigations and mining in the emerging Candida spp. are required to decipher their pathogenicity and virulence mechanisms compared to the prominent C. albicans. Lay Abstract Candida virulence factors (VFs) including mainly enzymes and proteins play vital roles in breaching the human intestinal barrier and causing deadly candidiasis. Limited VFs’ structural studies hinder deeper comprehension of their mechanisms and thus the design of vaccines and antifungal drugs against fungal infections.


Author(s):  
Ashwini S. Kaware ◽  
Pramod U Ingle ◽  
Aniket K. Gade ◽  
Mahendra Rai

Introduction: Alternaria spp. and Candida spp. are the main fungal pathogen of indoor environment like house, office, classroom, etc. These may cause various diseases and infections like systemic infections, or chronic asthma in immunocompromised individuals through secretion of various toxic substances. Chemical-based commercially available room fresheners used to control the fungal load of indoor environment are not beneficial to human health. Objective: was to provide viable alternative in the form of nanoparticle-based approach for the management of air-borne fungi. Methodology: The present study primarily focuses on the isolation, microscopic and biochemical identification of indoor fungi; Azadirachta indica-mediated sulphur nanoparticles (SNPs) synthesis, their detection and characterization; and in vitro assessment of SNPs against isolated fungi present in indoor environment. Result: The isolated fungi were identified as Alternaria spp and Candida spp. The SNPs showed absorbance maxima at 291 nm. NTA analysis showed average size of 188.4 nm, and zeta potential of -4.94 mV which represented synthesis of stable SNPs. XRD pattern confirmed the face centered cubic, crystalline nature of SNPs. FTIR spectrum depicted the presence of polyhydroxyl, nitrile, keto, aromatic and carboxylic compounds which stabilized the SNPs. The antifungal assays demonstrated the significant activity of the formulated SNPs and eucalyptus oil infused air freshener. Conclusion: It can be concluded that A. indica-mediated SNPs can be applied in the formulation and manufacture of an ecofriendly air freshener for the management of indoor fungal pathogens like Alternaria spp. and Candida spp.


10.5772/23456 ◽  
2011 ◽  
Author(s):  
Berenice Parra-Ortega ◽  
Lourdes Villa-Tanaca ◽  
Cesar Hernandez-Rodriguez

2019 ◽  
Vol 5 (3) ◽  
pp. 67 ◽  
Author(s):  
Friedman ◽  
Schwartz

: The landscape of clinical mycology is constantly changing. New therapies for malignant and autoimmune diseases have led to new risk factors for unusual mycoses. Invasive candidiasis is increasingly caused by non-albicans Candida spp., including C. auris, a multidrug-resistant yeast with the potential for nosocomial transmission that has rapidly spread globally. The use of mould-active antifungal prophylaxis in patients with cancer or transplantation has decreased the incidence of invasive fungal disease, but shifted the balance of mould disease in these patients to those from non-fumigatus Aspergillus species, Mucorales, and Scedosporium/Lomentospora spp. The agricultural application of triazole pesticides has driven an emergence of azole-resistant A. fumigatus in environmental and clinical isolates. The widespread use of topical antifungals with corticosteroids in India has resulted in Trichophyton mentagrophytes causing recalcitrant dermatophytosis. New dimorphic fungal pathogens have emerged, including Emergomyces, which cause disseminated mycoses globally, primarily in HIV infected patients, and Blastomyces helicus and B. percursus, causes of atypical blastomycosis in western parts of North America and in Africa, respectively. In North America, regions of geographic risk for coccidioidomycosis, histoplasmosis, and blastomycosis have expanded, possibly related to climate change. In Brazil, zoonotic sporotrichosis caused by Sporothrix brasiliensis has emerged as an important disease of felines and people.


2020 ◽  
Vol 6 (4) ◽  
pp. 348
Author(s):  
Isabella Zangl ◽  
Reinhard Beyer ◽  
Ildiko-Julia Pap ◽  
Joseph Strauss ◽  
Christoph Aspöck ◽  
...  

Several Candida species are opportunistic human fungal pathogens and thrive in various environmental niches in and on the human body. In this study we focus on the conditions of the vaginal tract, which is acidic, hypoxic, glucose-deprived, and contains lactic acid. We quantitatively analyze the lactic acid tolerance in glucose-rich and glucose-deprived environment of five Candida species: Candidaalbicans, Candida glabrata, Candida parapsilosis, Candida krusei and Candida tropicalis. To characterize the phenotypic space, we analyzed 40–100 clinical isolates of each species. Each Candida species had a very distinct response pattern to lactic acid stress and characteristic phenotypic variability. C. glabrata and C. parapsilosis were best to withstand high concentrations of lactic acid with glucose as carbon source. A glucose-deprived environment induced lactic acid stress tolerance in all species. With lactate as carbon source the growth rate of C. krusei is even higher compared to glucose, whereas the other species grow slower. C. krusei may use lactic acid as carbon source in the vaginal tract. Stress resistance variability was highest among C. parapsilosis strains. In conclusion, each Candida spp. is adapted differently to cope with lactic acid stress and resistant to physiological concentrations.


2019 ◽  
Vol 14 (13) ◽  
pp. 1159-1170
Author(s):  
Anjna Kumari ◽  
Rachna Singh

Staphylococci are common inhabitants at several human body sites and are also implicated in infections either as primary or opportunistic pathogens. These bacteria can thus both contribute to the host defense being a part of the commensalistic microbiota or synergize with the other microbes during the infection process. Among fungi, staphylococci interact synergistically with Candida spp. and Aspergillus fumigatus, and antagonistically with Cryptococcus neoformans and Trichosporon asahii. These interactions are highly dynamic and are orchestrated by a multitude of microbial and host factors. During such cross-talks, staphylococci can modulate the virulence, immune response or drug resistance of the coexisting microbe(s), thereby influencing the infection course, disease severity, treatment strategy and the clinical outcome.


Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1722 ◽  
Author(s):  
Justyna Karkowska-Kuleta ◽  
Kamila Kulig ◽  
Elzbieta Karnas ◽  
Ewa Zuba-Surma ◽  
Olga Woznicka ◽  
...  

Candida spp. yeast-like fungi are opportunistic pathogens in humans and have been recently found to release extracellular vesicles (EVs) that are involved in many vital biological processes in fungal cells. These include communication between microorganisms and host–pathogen interactions during infection. The production of EVs and their content have been significantly characterized in the most common candidal species Candida albicans, including the identification of numerous virulence factors and cytoplasmic proteins in the EV cargo. We have here conducted the isolation and proteomic characterization of EVs produced by the clinically important non-albicans Candida species C. glabrata, C. tropicalis and C. parapsilosis. With the use of ultracentrifugation of the cell-free culture supernatant, the candidal EVs were collected and found to be a heterogeneous population of particles for each species with sizes ranging from 60–280 nm. The proteinaceous contents of these vesicles were analyzed using LC-MS/MS, with particular attention paid to surface-expressed proteins that would come into immediate and direct contact with host cells. We thereby identified 42 extracellular and surface-connected proteins from C. glabrata, 33 from C. parapsilosis, and 34 from C. tropicalis, including membrane-associated transporters, glycoproteins and enzymes involved in the organization of the fungal cell wall, as well as several cytoplasmic proteins, including alcohol dehydrogenase, enolase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase and pyruvate kinase, for which the vesicular transport is a possible mechanism underlying their non-classical secretion.


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