The role of the cell wall in fungal pathogenesis

Arana, David M.; Prieto, Daniel; Román, Elvira; Nombela, César; Alonso-Monge, Rebeca; Pla, Jesús

doi:10.1111/j.1751-7915.2008.00070.x

Cited by 67 publications

(62 citation statements)

References 128 publications

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“…hog1 and pbs2 mutants are sensitive to both ionic and nonionic osmotic stresses (San José et al, 1996;Arana et al, 2005). Upon addition of sodium chloride, Hog1 becomes phosphorylated in a Pbs2-dependent manner and translocates to the nucleus of the cell (Alonso- Monge et al, 2003;Smith et al, 2004;Arana et al, 2005).…”

Section: The Hog Pathwaymentioning

confidence: 99%

“…hog1 and pbs2 mutants display enhanced true hyphal formation as evidenced under non-inducing conditions such as low temperature, low pH on certain media or even liquid media with limited serum concentration (Alonso-Monge et al, 1999; Arana et al, 2005). In contrast, ssk1 mutants also have a reduced ability to form hyphae on serum and these phenotypes are not suppressed by Hog1 overexpression (Alex et al, 1998;Calera et al, 2000).…”

Section: The Hog Pathwaymentioning

confidence: 99%

“…Recent studies also indicate that the pattern of Mkc1 activation (despite the fact of the existence of the TEY motif, characteristic of cell growth MAPKs, instead of the TGY motif, characteristic of stress MAPKs: Kultz & Burg, 1998) closely resembles that of the general stress-activated kinases. In fact, Mkc1 is phosphorylated in response to oxidative stress, osmotic stress, antifungal drugs, calcium ions and low-temperature shocks among others (Navarro-García et al 2005) and its oxidativestress-mediated phosphorylation is partially dependent on an intact HOG pathway (Arana et al, 2005;Navarro-Garcia et al, 2005). Mkc1 therefore behaves similarly to Mkp1, an Slt2 homologue in Pneumocystis carinii (Fox & Smulian, 1999) and to S. cerevisiae Slt2 (Vilella et al, 2005), in both cases being also activated by oxidative stress.…”

Section: The Cell Integrity Pathwaymentioning

confidence: 99%

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The MAP kinase signal transduction network in Candida albicans

et al. 2006

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MAP (mitogen-activated protein) kinase-mediated pathways are key elements in sensing and transmitting the response of cells to environmental conditions by the sequential action of phosphorylation events. In the fungal pathogen Candida albicans, different routes have been identified by genetic analysis, and especially by the phenotypic characterization of mutants altered in the Mkc1, Cek1/2 and Hog1 MAP kinases. The cell integrity (or MKC1-mediated) pathway is primarily involved in the biogenesis of the cell wall. The HOG pathway participates in the response to osmotic stress while the Cek1 pathway mediates mating and filamentation. Their actual functions are, however, much broader and Mkc1 senses several types of stress, while Hog1 is also responsive to other stress conditions and participates in two morphogenetic programmes: filamentation and chlamydospore formation. Furthermore, it has been recently shown that Cek1 participates in a putative pathway involved in the construction of the cell wall and which seems to be operative under basal conditions. As these stimuli are frequently encountered in the human host, they provide a reasonable explanation for the significant reduction in pathogenicity that several signal transduction mutants show in certain animal models of virulence. MAPK pathways therefore represent an attractive multienzymic system for which novel antifungal therapy could be designed.

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Section: The Hog Pathwaymentioning

confidence: 99%

Section: The Hog Pathwaymentioning

confidence: 99%

Section: The Cell Integrity Pathwaymentioning

confidence: 99%

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The MAP kinase signal transduction network in Candida albicans

et al. 2006

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“…Most receptoreligand interactions between Mf's and microorganisms lead to the destruction of the pathogen, although certain interactions allow for a permissive environment in which the pathogen can survive and proliferate [8]. Some receptors such as the mannose receptor (MR), scavenger receptors, and b-glucan receptors may identify specific pathogen-associated motifs, generally carbohydrates, and mediate non-opsonic phagocytosis [9]. Some molecules of the host, like opsonins [10], bind to the surface of microorganisms and promote microbial clearance through activation of phagocytosis.…”

Section: Introductionmentioning

confidence: 99%

Phagocytic receptors on macrophages distinguish between different Sporothrix schenckii morphotypes

Guzmán-Beltrán

Pérez‐Torres

Coronel-Cruz

et al. 2012

Microbes and Infection

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“…Furthermore, shuttling of conidia was conserved between two opportunistic fungal pathogen species, but the kinetics of shuttling was pathogen-specific. This suggested that shuttling was driven by a component common to the conidial cell wall of both species, but one present at different levels or exposed to phagocytes to different degrees [30]. Shuttling of zymosan particles provided further evidence locating a shuttling trigger to the cell wall (Fig 5A,C), leading β-glucan to be identified as a fungal-derived signal sufficient to drive shuttling of plastic beads (Fig 5B,D).…”

Section: Discussionmentioning

confidence: 99%

β-glucan dependent shuttling of conidia from neutrophils to macrophages occurs during fungal infection establishment

Pazhakh

Ellett

O’Donnell

et al. 2019

Preprint

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41The initial host response to fungal pathogen invasion is critical to infection 42 establishment and outcome. However, the diversity of leukocyte-pathogen 43 interactions is only recently being appreciated. We describe a new form of inter-44 leukocyte conidial exchange called "shuttling". In Talaromyces marneffei and 45 Aspergillus fumigatus zebrafish in vivo infections, live imaging demonstrated 46 conidia initially phagocytosed by neutrophils were transferred to macrophages.47 Shuttling is unidirectional, not a chance event, involves alterations of phagocyte 48 mobility, inter-cellular tethering, and phagosome transfer. Shuttling kinetics 49 were fungal species-specific, implicating a fungal determinant. β-glucan serves as 50 a fungal-derived signal sufficient for shuttling. Murine phagocytes also shuttled 51 in vitro. The impact of shuttling for microbiological outcomes of in vivo infections 52 is difficult to specifically assess experimentally, but for these two pathogens, 53 shuttling augments initial conidial redistribution away from fungicidal 54 neutrophils into the favourable macrophage intracellular niche. Shuttling is a 55 frequent host/pathogen interaction contributing to fungal infection 56 establishment patterns. 57 58 59 150 words / 150 words allowed 60 61 Pazhakh et al: Fungal spore shuttling between phagocytes Page 3/58 62 Introduction63 In vertebrates, two phagocytic cell types have long been recognized as key 64 players in the initial host defense response to infection: neutrophil granulocytes 65 and macrophages [1]. Neutrophils and macrophages share many features: they 66 are both migratory cells, they phagocytose microorganisms on encountering 67 them, and they have intracellular mechanisms for killing microorganisms.68 However, although both phagocyte types engulf microorganisms, individual 69 microorganisms interact with neutrophils and macrophages with different 70 species-specific preferences, in different ways, and using different molecular 71 mechanisms [2]. Conversely, the host has evolved diverse cellular strategies for 72 these two different phagocytes to protect against the panoply of potentially 73 pathogenic microorganisms. 74 75 The exchange of cytoplasmic material through contact-dependent mechanisms 76 between adjacent cells is currently a topical field in cell biology. An example is 77 the contact-dependent exchange of cytoplasm from macrophage to tumor cells as 78 a metastasis-promoting mechanism [3], distinct from the cytoplasmic exchange 79 between macrophages and tumor cells that occur via extracellular vesicles and 80 nanotubes [4-6].81 82 During infections, neutrophils and macrophages also engage in intercellular 83 exchanges. Some microorganisms have evolved mechanisms that exploit these to 84 enhance their pathogenicity and promote their spread between phagocytes. For 85 example, Yersinia pestis and Leishmania promastigotes induce apoptosis in host 86 neutrophils to then exploit efferocytosis, whereby clearance of dead neutrophils Pazhakh et al: Fungal spore shuttling...

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The role of the cell wall in fungal pathogenesis

Cited by 67 publications

References 128 publications

The MAP kinase signal transduction network in Candida albicans

The MAP kinase signal transduction network in Candida albicans

Phagocytic receptors on macrophages distinguish between different Sporothrix schenckii morphotypes

β-glucan dependent shuttling of conidia from neutrophils to macrophages occurs during fungal infection establishment

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