Control of Filament Formation in Candida albicans by Polyamine Levels

Abstract

Candida albicans, the most common fungal pathogen, regulates its cellular morphology in response to environmental conditions. The ODC gene, which encodes ornithine decarboxylase, a key enzyme in polyamine biosynthesis, was isolated and disrupted. Homozygous null Candida mutants behaved as polyamine auxotrophs and grew exclusively in the yeast form at low polyamine levels (0.01 mM putrescine) under all conditions tested. An increase in the polyamine concentration (10 mM putrescine) restored the capacity to switch from the yeast to the filamentous form. The strain with a deletion mutation also showed increased sensitivity to salts and calcofluor white. This Candida odc/odc mutant was virulent in a mouse model. The results suggest a model in which polyamine levels exert a pleiotrophic effect on transcriptional activity.

Ustilago maydis spermidine synthase is encoded by a chimeric gene, required for morphogenesis, and indispensable for survival in the host

“…Moreover, dimorphic transition of Dodc mutants required putrescine concentrations higher than those necessary to support fungal growth (Guevara-Olvera et al, 1997), suggesting a specific role of polyamines in dimorphism. Similar results were obtained with Dodc mutants of Candida albicans (Herrero et al, 1999) and Yarrowia lipolytica (Jiménez-Bremont et al, 2001). Nevertheless, it was not possible to demonstrate as to loss of which of the several polyamines was responsible for the resulting phenotype.…”

“…As observed in spe mutants from other fungi, U. maydis single (spe-sdh) mutants were auxotrophic to spermidine, but were able to grow in the absence of spermidine for three cycles, as described for S. cerevisiae (Balasundaram et al, 1991) and C. albicans (Herrero et al, 1999), probably because they accumulate polyamine pools in the vacuole , cytosol, and/or nuclei (Davis et al, 1992). Of particular importance was the observation that double mutants did not accumulate high concentrations of putrescine, suggesting the existence of a mechanism that controlled its cellular levels under conditions that avoided its transformation into spermidine.…”

Methionine is required for cAMP‐PKA‐mediated morphogenesis and virulence of Candida albicans

“…Polyamines are synthesized by decarboxylation of ornithine, forming putrescine. Inhibition or deletion of ornithine decarboxylase (ODC) strongly affects hyphae induction in vitro (Herrero et al, 1999;Ueno et al, 2004). Inhibition of this gene reduces basal cAMP levels, as well as CYR1 mRNA expression, linking polyamine-induced filamentation to the PKA pathway (Ueno et al, 2004).…”

In vivoinfluence ofin vitroup-regulated genes in the virulence of an APEC strain associated with swollen head syndrome

“…An attenuation of the mutants in polyamine transporters was also verified in the work of Ware et al (2006) where the inactivation of the potD gene in pneumococcus greatly decreased the pathogenesis of the bacteria within the host, regardless of the inoculation route or whether the infection was septicaemia or pneumonia (Ware et al, 2006). The polyamine putrescine has been shown to restore virulence gene expression in Shigella flexneri (Durand & Bjork, 2003), to influence the formation of filaments that are necessary for virulence in Candida albicans (Herrero et al, 1999) and to be involved in host cell adherence by Trichomonas vaginalis (Garcia et al, 2005), as presented in this work. Polyamines in general also play a central role in the virulence of other intracellular pathogens, including Francisella tularensis and Legionella pneumophila (Carlson et al, 2009;Nasrallah et al, 2011;Russo et al, 2011).…”