Secreted proteases from pathogenic fungi

Monod, Michel; Capoccia, Sabrina; Léchenne, Barbara; Zaugg, Christophe; Holdom, Mary D.; Jousson, Olivier

doi:10.1078/1438-4221-00223

Cited by 324 publications

(267 citation statements)

References 149 publications

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“…As both fungi secrete a variety of proteases in vivo and in vitro , 7 and microbial proteases are known to activate PAR receptors, 9 we assessed whether the ability of Aspergillus culture supernatant to inhibit trypsin signaling was sensitive to protease inhibition. For this purpose, supernatants from both Candida and Aspergillus were treated with protease inhibitors and used to assess [Ca 2 + ] i mobilization in HEK293 in response to thrombin and trypsin, respectively.…”

Section: Fungal Proteases Contribute To Par Activationmentioning

confidence: 99%

The contribution of PARs to inflammation and immunity to fungi

et al. 2008

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During inflammation, host-and microbial-derived proteases trigger the activation of protease-activated receptors (PARs), a family of G-protein-coupled receptors. We report here that activation of Toll-like receptors (TLRs) by fungi unmasks an essential and divergent role for PAR 1 and PAR 2 in downstream signaling and inflammation. TLRs activated PARs and triggered distinct signal transduction pathways involved in inflammation and immunity to Candida albicans and Aspergillus fumigatus. Inflammation was promoted by PAR 1 and PAR 2 activation in response to Candida and by PAR 2 inhibition in response to Aspergillus . This occurred by TLR regulation of PAR signaling, with TLR2 promoting PAR 1 activity, and TLR4 suppressing PAR 2 activity. Thus, tissue injury and pathogens induce signals that are integrated at the level of distinct TLR / PAR-dependent pathways, the exploitation or subversion of which contributes to divergence in microbial promotion of inflammatory response.

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Section: Fungal Proteases Contribute To Par Activationmentioning

confidence: 99%

The contribution of PARs to inflammation and immunity to fungi

et al. 2008

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“…These enzymes play a role in nutrition, tissue damage, fungal dissemination within the human body, iron acquisition and overcoming the host immune system, all of which strongly affect fungal pathogenicity [53]. Secretion of enzymes into extracellular environments might be an important adaptive mechanism during the fungal life cycle [54]. It is logical to suppose that these enzymes act by facilitating tissue invasion, but they can also participate in causing infection by impairing some mechanisms of the immune system and/or assisting in obtaining nutrients, thus causing injury to the host [55,56].…”

Section: Extracellular Enzyme Pathogenicitymentioning

confidence: 99%

Targeted Inspection of Environmental Mycological Load for Mitigation of Indoor Mold toward Improved Public Health

Masaphy¹,

Ezr²

2016

J Microb Biochem Technol

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“…Collectively, proteases participate in different steps of the multifaceted interaction events between microorganism and host structures, being considered as virulent attributes. Consequently, the biochemical characterization of these proteolytic enzymes is of interest not only for understanding proteases in general but also for understanding their roles in microbial infections and thus their exploitation as targets for rational chemotherapy of microbial diseases [3,6,10,[18][19][20][21][22][23][24] .…”

Section: Proteases Produced By Microorganisms: Global Functionsmentioning

confidence: 99%

“…Due to the emergence of pathogens resistant to conventional antifungals and the toxicity of some antimycotics, intense efforts have been made to develop more effective antifungal agents for clinical use [44][45][46][47][48] . The pathogenesis of C. albicans is multifactorial and different virulence attributes are important during the various stages of infection [20,21,[49][50][51][52][53][54][55] . Secreted aspartic proteases (Saps) play a role in several infection stages of C. albicans, being the most important virulence factors expressed by this opportunistic fungus.…”

Section: Tripeptidyl Peptidases Dipeptidyl Peptidasesmentioning

confidence: 99%

Protease expression by microorganisms and its relevance to crucial physiological/pathological events

Santos¹

2011

WJBC

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The treatment of infections caused by fungi and trypanosomatids is difficult due to the eukaryotic nature of these microbial cells, which are similar in several biochemical and genetic aspects to host cells. Aggravating this scenario, very few antifungal and anti-trypanosomatidal agents are in clinical use and, therefore, therapy is limited by drug safety considerations and their narrow spectrum of activity, efficacy and resistance. The search for new bioactive agents against fungi and trypanosomatids has been expanded because progress in biochemistry and molecular biology has led to a better understanding of important and essential pathways in these microorganisms including nutrition, growth, proliferation, signaling, differentiation and death. In this context, proteolytic enzymes produced by these eukaryotic microorganisms are appointed and, in some cases, proven to be excellent targets for searching novel natural and/or synthetic pharmacological compounds, in order to cure or prevent invasive fungal/trypanosomatid diseases. With this task in mind, our research group and others have focused on aspartic-type proteases, since the activity of this class of hydrolytic enzymes is directly implicated in several facets of basic biological processes of both fungal and trypanosomatid cells as well as due to the participation in numerous events of interaction between these microorganisms and host structures. In the present paper, a concise revision of the beneficial effects of aspartic protease inhibitors, with emphasis on the aspartic protease inhibitors used in the anti-human immunodeficiency virus therapy, will be presented and discussed using our experience with the following microbial models: the yeast Candida albicans , the filamentous fungus Fonsecaea pedrosoi and the protozoan trypanosomatid Leishmania amazonensis .

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Secreted proteases from pathogenic fungi

Cited by 324 publications

References 149 publications

The contribution of PARs to inflammation and immunity to fungi

The contribution of PARs to inflammation and immunity to fungi

Targeted Inspection of Environmental Mycological Load for Mitigation of Indoor Mold toward Improved Public Health

Protease expression by microorganisms and its relevance to crucial physiological/pathological events

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