Contributions of hyphae and hypha-co-regulated genes to Candida albicans virulence

Abstract

SummaryThe fascinating ability of Candida albicans to undergo dramatic changes in cellular morphology has invited speculation that this plasticity in form contributes to the virulence of the organism. Molecular genetic analyses have confirmed this hypothesis and further demonstrated that genes that govern cellular morphology are co-regulated with genes encoding conventional virulence factors such as proteases and adhesins. The transcriptional regulatory networks of C. albicans thus ensure that hyphae are produced concomitantly with virulence factors, resulting in cells that are adapted for invading the tissues of an immunocompromised host. Hyphae are able to exert mechanical force, aiding penetration of epithelial surfaces, and hyphae damage endothelial cells, aiding escape of C. albicans from the host bloodstream into deeper tissue. Hyphal morphogenesis is thus an integral part of the overall virulence strategy of C. albicans .Unlike highly specialized pathogens that express a single major virulence factor (e.g. Clostridium tetani ), the opportunistic fungal pathogen Candida albicans expresses a repertoire of activities that contribute to virulence. The sum of the effects of many Candida factors leads to the establishment of infection in a suitably compromised host. In some host niches, particular fungal proteins (e.g. adhesins) are important, while in other niches, these proteins are less important and other factors play a dominant role. By being adapted for growth in many possible host niches, C. albicans is able to cause the wide spectrum of clinical manifestations for which is it known.Discussions of C. albicans virulence factors usually include dimorphism, the ability to grow in more than one morphological form. C. albicans grows either as budding yeast cells or as filamentous hyphae (chains of elongated, parallel-sided cells lacking constrictions at the septa) or pseudohyphae (chains of variably elongated cells with constrictions at the septa). Because of their similar elongated shapes and the many conditions and regulators that are shared in common, the hyphal and pseudohyphal forms are often not distinguished in the literature; the more general term, 'filamentous forms', is used to refer to both. The two morphologies, however, are fundamentally different and can be distinguished by a number of characteristics. The distinctions between the two forms have been elegantly reviewed by Sudbery et al . (2004).Filamentation is believed to be important for virulence and thus, morphogenesis in this fungus has been a subject of considerable study. The potential roles of the hyphal form, in particular, in virulence have also been discussed frequently in the literature. While most mutants that fail to produce hyphae are compromised in virulence, several authors have pointed out that co-regulation of genes controlling hyphal morphogenesis with genes encoding virulence factors confounds the analysis (Kobayashi and Cutler, 1998;Brown, 2002;Gow et al ., 2002;Liu, 2002). Thus, it has been difficult to determine unequivoc...

Identification of anN-Acetylglucosamine Transporter That Mediates Hyphal Induction inCandida albicans

“…In C. albicans, GlcNAc induces the formation of hyphal cells, which is an underlying virulence trait as budding and hyphal cells are thought to carry out unique roles during infection. In addition to different morphologies, budding and hyphal cells differ in the expression of virulence factors (Nantel et al, 2002;Lorenz et al, 2004), such as adhesin proteins, secreted hydrolytic enzymes, and antioxidant enzymes (Hube, 2004;Whiteway and Oberholzer, 2004;Kumamoto and Vinces, 2005). Therefore, in this study we used mass spectrometry to identify plasma membrane proteins in budding cells and GlcNAc-stimulated hyphae, which have the potential to mediate interaction with the host environment and contribute to the infectious process.…”

“…For example, small buds are more likely to disseminate in the bloodstream and hyphal cells may be better suited for invasive growth into tissues. The distinct cell types also differ in their production of virulence factors, such as the adhesin proteins that mediate attachment to host cells and secreted hydrolytic enzymes that facilitate invasive growth (Whiteway and Oberholzer, 2004;Kumamoto and Vinces, 2005).…”

Ocorrência e Perfil de Suscetibilidade de Candida sp em hemoculturas de um hospital universitário

“…13 A explicação para o fato de C. albicans apresentar os maiores percentuais de recuperação pode estar relacionada à sua grande adaptabilidade e versatilidade patogênica. 14 Ainda em nosso estudo, conduzido em Pouso Alegre, sul de Minas Gerais, foi possível observar que o número de amostras de hemocultura que o Laboratório de Microbiologia recebe, é homogêneo, sofrendo pouca variação no decorrer da pesquisa.…”

Amino acids mediate colony and cell differentiation in the fungal pathogen Candida parapsilosis

“…However, the molecular determinants of this differentiation have not yet been identified, mostly due to the lack of genetic tools for targeted disruption. Serum is also the most effective inducer of filamentous growth in C. albicans, and the signal transduction pathways activated by serum have been well characterized in this organism (for a review see Kumamoto & Vinces, 2005). Early investigations in C. albicans suggested that the serum inducing factor(s) was heat stable and nondialysable, and that the peak of serum induction activity co-migrated with the serum albumin fraction in gel filtration purification assays (Barlow et al, 1974;Buckley & Van Uden, 1963;Reynolds & Braude, 1956).…”