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Candida and Complement: New Aspects in an Old Battle.

ABSTRACT: Candida is a dominant fungal pathogen in immunocompromised hosts, leading to opportunistic infections. Complement with its multifaceted functions is involved in the immune defense against this yeast, and recently several novel aspects have emerged in this old battle. It is clear that Candida can adopt both roles as a colonizer or as a pathogen. In our article, we focus on the molecular mechanisms of the Candida-complement interplay, which occur in disseminated disease as well as locally on skin or on mucous membranes in mouth and vagina; the mechanisms can be supposed to be the same. Activation of the complement system by Candida is facilitated by directly triggering the three dominant pathways, but also indirectly via the coagulation and fibrinolysis systems. The complement-mediated anti-Candida effects induced thereby clearly extend chemotaxis, opsonization, and phagocytosis, and even the membrane attack complex formed on the fungal surface plays a modulatory role, although lysis of the yeast per se cannot be induced due to the thick fungal cell wall. In order to avoid the hostile action of complement, several evasion mechanisms have evolved during co-evolution, comprising the avoidance of recognition, and destruction. The latter comes in many flavors, in particular the cleavage of complement proteins by yeast enzymes and the exploitation of regulatory proteins by recruiting them on the cell wall, such as factor H. The rationale behind that is that the fluid phase regulators on the fungal cell surface down-regulate complement locally. Interestingly, however, evasion protein knockout strains do not necessarily lead to an attenuated disease, so it is likely more complex in vivo than initially thought. The interactions between complement and non-albicans species also deserve attention, especially Candida auris, a recently identified drug-resistant species of medical importance. This is in particular worth investigating, as deciphering of these interactions may lead to alternative anti-fungal therapies directly targeting the molecular mechanisms.

SUBMITTER: Harpf V

PROVIDER: S-EPMC7381207 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Candida and Complement: New Aspects in an Old Battle.

Harpf Verena V Rambach Günter G Würzner Reinhard R Lass-Flörl Cornelia C Speth Cornelia C

Frontiers in immunology 20200714

Candida is a dominant fungal pathogen in immunocompromised hosts, leading to opportunistic infections. Complement with its multifaceted functions is involved in the immune defense against this yeast, and recently several novel aspects have emerged in this old battle. It is clear that Candida can adopt both roles as a colonizer or as a pathogen. In our article, we focus on the molecular mechanisms of the Candida-complement interplay, which occur in disseminated disease as wel ...[more]

PMID: 32765510

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Project description:Classical old-field succession studies focused on vegetation changes after the abandonment of annual croplands or on succession after the elimination of cultivated crops. Perennial-crop-mediated succession, where fields are initially covered by perennial crops, reveals alternative aspects of old-field succession theories. We tested the validity of classical theories of old-field succession for perennial-crop-mediated succession. We formulated the following hypotheses: (1) functional diversity increases with increasing field age; (2) resource acquisition versus conservation trade-off shifts toward conservation at community level during the succession; (3) the importance of spatial and temporal seed dispersal decreases during the succession; and (4) competitiveness and stress-tolerance increases and ruderality decreases at community level during the succession. We studied functional diversity, trait distributions and plant strategies in differently aged old-fields using chronosequence method. We found increasing functional richness and functional divergence, but also unchanged or decreasing functional evenness. We detected a shift from resource acquisition to resource conservation strategy of communities during the succession. The role of spatial and temporal seed dispersal was found to be important not only at the initial but also at latter successional stages. We found an increasing stress-tolerance and a decreasing ruderality during succession, while the competitiveness remained unchanged at the community level. Despite the markedly different starting conditions, we found that classical and perennial-crop-mediated old-field successions have some similarities regarding the changes of functional diversity, resource acquisition versus conservation trade-off, and seed dispersal strategies. However, we revealed also the subsequent differences. The competitive character of communities remained stable during the succession; hence, the initial stages of perennial-crop-mediated succession can be similar to the middle stages of classical old-field succession. Moreover, the occupied functional niche space and differentiation were larger in the older stages, but resources were not effectively utilized within this space, suggesting that the stabilization of the vegetation requires more time.

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Candida and Complement: New Aspects in an Old Battle.

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<i>Candida</i> and Complement: New Aspects in an Old Battle.

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