Interaction of pathogenic fungi with host cells: Molecular and cellular approaches

Abstract

This review provides an overview of several molecular and cellular approaches that are likely to supply insights into the host-fungus interaction. Fungi present intra- and/or extracellular host-parasite interfaces, the parasitism phenomenon being dependent on complementary surface molecules. The entry of the pathogen into the host cell is initiated by the fungus adhering to the cell surface, which generates an uptake signal that may induce its cytoplasmatic internalization. Furthermore, microbial pathogens use a variety of their surface molecules to bind to host extracellular matrix (ECM) components to establish an effective infection. On the other hand, integrins mediate the tight adhesion of cells to the ECM at sites referred to as focal adhesions and also play a role in cell signaling. The phosphorylation process is an important mechanism of cell signaling and regulation; it has been implicated recently in defense strategies against a variety of pathogens that alter host-signaling pathways in order to facilitate their invasion and survival within host cells. The study of signal transduction pathways in virulent fungi is especially important in view of their putative role in the regulation of pathogenicity. This review discusses fungal adherence, changes in cytoskeletal organization and signal transduction in relation to host-fungus interaction.

Innovation of the Parasitic Cycle of Coccidioides spp.

“…Histidine kinase functions as a global regulator of dimorphism and virulence in pathogenic fungi. Protein phosphorylation is generally accepted as playing a key role in transducing the signals involved in several processes such as cell adhesion, internalization, and killing of pathogens (Johannesson et al, 2006;Mendes-Giannini et al, 2005;Nemecek et al, 2006Nemecek et al, , 2007. We suggest that histidine kinases sense environmental signals such as temperature, CO 2 concentration, and pH and that they play key roles regulating Coccidioides spp.…”

“…In addition, this glycoprotein is an immunodominant antigen that is capable of eliciting both humoral and cellular responses in infected patients. Thus, SOWgp acts as an adhesin and modulates the host immune response (Hung et al, 2002;Klein & Tebbets 2007;Mendes-Giannini et al, 2005).…”

“…At maturity, the spherule ruptures, releasing the endospores (Figure 4), which measure 2-4 µm in diameter. The high fecundity of C. immitis is a feature that contributes to the aggressive nature of this primary human fungal pathogen (Mendes-Giannini et al, 2005). Thus, at any given point, the infected host is exposed to immature, mature, and rupturing spherules, newly released endospores, arthroconidia, and mycelial forms ( Figure 5).…”

Interactions of Paracoccidioides brasiliensis with host cells: recent advances

“…Many fungal pathogens, such as P. brasiliensis, have multiple virulence factors that can damage host defenses, and thus, contribute to an overall virulence phenotype for that organism. At the moment, the attachment, colonization, and dissemination of the etiological agent are considered to be the crucial stages in the onset of disseminated mycosis [10,11].…”

Kinetic modeling of Toxoplasma gondii invasion

“…The rewards of this lifestyle include access to host cell machinery, evasion of the immune system, and scavenging of nutrients and energy. Organisms that exploit this lifestyle are found among all major groups of pathogens, including viruses, bacteria, protozoa, fungi and helminthes (Andrade & Andrews, 2005, Despommier, 1998, Mendes-Giannini et al, 2005, Pizarro-Cerda & Cossart, 2006, Sibley, 2004, Sieczkarski & Whittaker, 2005. To gain access to intracellular resources obligate intracellular pathogens cross their host cell's plasma membrane using a variety of pathogenspecific mechanisms (Andrade & Andrews, 2005, Carruthers & Boothroyd, 2007, PizarroCerda & Cossart, 2006, Sieczkarski & Whittaker, 2005, Sieczkarski & Whittaker, 2005, Soldati et al, 2004.…”