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      Divergent Approaches to Virulence in C. albicans and C. glabrata: Two Sides of the Same Coin

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          Abstract

          Candida albicans and Candida glabrata are the two most prevalent etiologic agents of candidiasis worldwide. Although both are recognized as pathogenic, their choice of virulence traits is highly divergent. Indeed, it appears that these different approaches to fungal virulence may be equally successful in causing human candidiasis. In this review, the virulence mechanisms employed by C. albicans and C. glabrata are analyzed, with emphasis on the differences between the two systems. Pathogenesis features considered in this paper include dimorphic growth, secreted enzymes and signaling molecules, and stress resistance mechanisms. The consequences of these traits in tissue invasion, biofilm formation, immune system evasion, and macrophage escape, in a species dependent manner, are discussed. This review highlights the observation that C. albicans and C. glabrata follow different paths leading to a similar outcome. It also highlights the lack of knowledge on some of the specific mechanisms underlying C. glabrata pathogenesis, which deserve future scrutiny.

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          Most cited references188

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          Recognition of microorganisms and activation of the immune response.

          The mammalian immune system has innate and adaptive components, which cooperate to protect the host against microbial infections. The innate immune system consists of functionally distinct 'modules' that evolved to provide different forms of protection against pathogens. It senses pathogens through pattern-recognition receptors, which trigger the activation of antimicrobial defences and stimulate the adaptive immune response. The adaptive immune system, in turn, activates innate effector mechanisms in an antigen-specific manner. The connections between the various immune components are not fully understood, but recent progress brings us closer to an integrated view of the immune system and its function in host defence.
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            Nonfilamentous C. albicans mutants are avirulent.

            Candida albicans and Saccharomyces cerevisiae switch from a yeast to a filamentous form. In Saccharomyces, this switch is controlled by two regulatory proteins, Ste12p and Phd1p. Single-mutant strains, ste12/ste12 or phd1/phd1, are partially defective, whereas the ste12/ste12 phd1/phd1 double mutant is completely defective in filamentous growth and is noninvasive. The equivalent cph1/cph1 efg1/efg1 double mutant in Candida (Cph1p is the Ste12p homolog and Efg1p is the Phd1p homolog) is also defective in filamentous growth, unable to form hyphae or pseudohyphae in response to many stimuli, including serum or macrophages. This Candida cph1/cph1 efg1/efg1 double mutant, locked in the yeast form, is avirulent in a mouse model.
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              Immune recognition. A new receptor for beta-glucans.

              The carbohydrate polymers known as beta-1,3-d-glucans exert potent effects on the immune system - stimulating antitumour and antimicrobial activity, for example - by binding to receptors on macrophages and other white blood cells and activating them. Although beta-glucans are known to bind to receptors, such as complement receptor 3 (ref. 1), there is evidence that another beta-glucan receptor is present on macrophages. Here we identify this unknown receptor as dectin-1 (ref. 2), a finding that provides new insights into the innate immune recognition of beta-glucans.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                11 May 2019
                May 2019
                : 20
                : 9
                : 2345
                Affiliations
                [1 ]Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal; monicagalocha@ 123456gmail.com (M.G.); pedrohpais@ 123456tecnico.ulisboa.pt (P.P.); mafalda.cavalheiro@ 123456tecnico.ulisboa.pt (M.C.); diana.pereira@ 123456tecnico.ulisboa.pt (D.P.); romeuviana@ 123456outlook.com (R.V.)
                [2 ]iBB-Institute for Bioengineering and Biosciences, Biological Sciences Research Group, Instituto Superior Técnico, University of Lisbon, Av. Rovisco Pais, 1049-001 Lisboa, Portugal
                Author notes
                [* ]Correspondence: mnpct@ 123456tecnico.ulisboa.pt ; Tel.: +351-218417772; Fax: +351-218419199
                Author information
                https://orcid.org/0000-0002-4090-7016
                https://orcid.org/0000-0001-5628-416X
                https://orcid.org/0000-0002-9644-5906
                https://orcid.org/0000-0002-5676-6174
                Article
                ijms-20-02345
                10.3390/ijms20092345
                6539081
                31083555
                02b36552-8378-4e48-8271-4175ae4804cb
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 10 April 2019
                : 08 May 2019
                Categories
                Review

                Molecular biology
                candida,host-pathogen interaction,virulence,biofilm formation,morphology,immune evasion

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