The NDR/LATS Kinase Cbk1 Controls the Activity of the Transcriptional Regulator Bcr1 during Biofilm Formation in Candida albicans

In nature, many microorganisms form specialized complex, multicellular, surface-attached communities called biofilms. These communities play critical roles in microbial pathogenesis. The fungal pathogen Candida albicans is associated with catheter-based infections due to its ability to establish biofilms. The transcription factor Bcr1 is a master regulator of C. albicans biofilm development, although the full extent of its regulation remains unknown. Here, we report that Bcr1 is a phosphoprotein that physically interacts with the NDR kinase Cbk1 and undergoes Cbk1-dependent phosphorylation. Mutating the two putative Cbk1 phosphoacceptor residues in Bcr1 to alanine markedly impaired Bcr1 function during biofilm formation and virulence in a mouse model of disseminated candidiasis. Cells lacking Cbk1, or any of its upstream activators, also had reduced biofilm development. Notably, mutating the two putative Cbk1 phosphoacceptor residues in Bcr1 to glutamate in cbk1Δ cells upregulated the transcription of Bcr1-dependent genes and partially rescued the biofilm defects of a cbk1Δ strain. Therefore, our data uncovered a novel role of the NDR/LATS kinase Cbk1 in the regulation of biofilm development through the control of Bcr1

Dinámica de septinas y regulación de la separación celular durante el crecimiento hifal de Candida albicans ¿una diana de antifúngicos?

Resumen del trabajo presentado al "IV Congreso GEBMP: Simposio Hongos Patógenos" celebrado en Badajoz el 6 de julio del 2012.Peer Reviewe

A membrane-associated form of the transcription factor Ace2 controls septin ring dynamics during Candida albicans hyphal growth

Resumen del trabajo presentado a la Vth International Conference on Molecular Mechanisms of Fungal Cell Wall Biogenesis celebrada en Primosten (Croacia) del 6 al 9 de Junio de 2012.Peer Reviewe

Integrating Cdk signaling in Candida albicans environmental sensing networks

El pdf del capítulo es la versión de autor.Cyclin-dependent protein kinases (Cdks) control cell cycle progression and morphological switches in eukaryotic cells. Based on recent findings concerning the evolution of Cdk phosphorylation sites in the Ascomycete linage, we shall analyze the density of Cdk motifs in the Candida proteome using the S LR algorithm, focusing on protein sequences of regulatory modules that play important roles in the environmental sensing of Candida albicans. Since Cdks are also involved in morphogenesis and environmental signaling, this search could help us to speculate about how Cdk signaling might be integrated in these regulatory networks that control C. albicans morphopathogenic determinants. © 2012 Springer-Verlag Berlin Heidelberg.This work was supported by grants from the Spanish Ministry of Science and Innovation to JCB (BFU2009-11251) and to CRV (BFU2010-15884) and the Regional Government of Extremadura (PRI08A017 and GRU09001) to JCB. The IBFG is institutionally supported by Fundación Ramón Areces.Peer Reviewe

Regulation of the cell cycle timing of Start in fission yeast by the rum1+ gene

We have identified the rum1+ gene as a new regulator of the G1-phase of the fission yeast cell cycle. rum1+ determines the cell cycle timing of Start, by maintaining cells in a pre-Start state until they have attained a minimal critical mass. Cells lacking rum1+ are unable to arrest in pre-Start G1 in response to nitrogen starvation and are subsequently sterile. In addition, rum1+ prevents entry into mitosis from pre-Start G1, as shown by the fact that cdc10 mutants in the absence of rum1+ undergo lethal mitosis without entering S-phase.Peer Reviewe

The Cdc14p phosphatase affects late cell-cycle events and morphogenesis in Candida albicans

14 pages, 10 figures.-- et al.We have characterized the CDC14 gene, which encodes a dual-specificity protein phosphatase in Candida albicans, and demonstrated that its deletion results in defects in cell separation, mitotic exit and morphogenesis. The C. albicans cdc14Δ mutants formed large aggregates of cells that resembled those found in ace2-null strains. In cdc14Δ cells, expression of Ace2p target genes was reduced and Ace2p did not accumulate specifically in daughter nuclei. Taken together, these results imply that Cdc14p is required for the activation and daughter-specific nuclear accumulation of Ace2p. Consistent with a role in cell separation, Cdc14p was targeted to the septum region during the M-G1 transition in yeast-form cells. Interestingly, hypha-inducing signals abolished the translocation of Cdc14p to the division plate, and this regulation depended on the cyclin Hgc1p, since hgc1Δ mutants were able to accumulate Cdc14p in the septum region of the germ tubes. In addition to its role in cytokinesis, Cdc14p regulated mitotic exit, since synchronous cultures of cdc14Δ cells exhibited a severe delay in the destruction of the mitotic cyclin Clb2p. Finally, deletion of CDC14 resulted in decreased invasion of solid agar medium and impaired true hyphal growth.M.S. and J.J. were supported by grants from the Junta de Castilla y León (SA013B05) and Ministerio de Ciencia y Tecnología (BIO2001-1345-C02-02). J.C.-B. was supported by grants from Ministerio de Ciencia y Tecnología (PM99-0182 and BMC2003-05758). A.C.-B. holds a fellowship from the Junta de Extremadura, and A.G.-N. and D.C.-L. from the Ministerio de Ciencia y Tecnología.Peer reviewe

Phosphoregulation of Nrg1 in Candida albicans

Trabajo presentado al Workshops Current Trends in Biomedicine: "Comparative and Functional Genomics on Fungal Pathogens" celebrado en la Universidad Internacional de Andalucía (Baeza, España) del 17 al 19 de Noviembbre de 2014.This work was supported by grants from the Spanish Ministry of Science and Innovation (BFU2012-39910) to J. C.-B and the Regional Government of Extremadura (GRU10008) to J. C.-B. All Spanish funding was co-sponsored by the European Union FEDER program.Peer reviewe

The Mitotic Cyclins Clb2p and Clb4p Affect Morphogenesis in Candida albicans

The ability of Candida albicans to switch cellular morphologies is crucial for its ability to cause infection. Because the cell cycle machinery participates in Saccharomyces cerevisiae filamentous growth, we characterized in detail the two C. albicans B-type cyclins, CLB2 and CLB4, to better understand the molecular mechanisms that underlie the C. albicans morphogenic switch. Both Clb2p and Clb4p levels are cell cycle regulated, peaking at G2/M and declining before mitotic exit. On hyphal induction, the accumulation of the G1 cyclin Cln1p was prolonged, whereas the accumulation of both Clb proteins was delayed when compared with yeast form cells, indicating that CLB2 and CLB4 are differentially regulated in the two morphologies and that the dynamics of cyclin appearance differs between yeast and hyphal forms of growth. Clb2p-depleted cells were inviable and arrested with hyper-elongated projections containing two nuclei, suggesting that Clb2p is not required for entry into mitosis. Unlike Clb2p-depleted cells, Clb4p-depleted cells were viable and formed constitutive pseudohyphae. Clb proteins lacking destruction box domains blocked cell cycle progression resulting in the formation of long projections, indicating that both Clb2p and Clb4p must be degraded before mitotic exit. In addition, overexpression of either B-type cyclin reduced the extent of filamentous growth. Taken together, these data indicate that Clb2p and Clb4p regulate C. albicans morphogenesis by negatively regulating polarized growth

The Rts1 regulatory subunit of PP2A is essential for septin organization in Candida albicans

Trabajo presentado en el Simposio Internacional: Las levaduras: en la intersección de la biología de sistemas y la biomedicina/ Yeasts: at the cross-roads of Systems biology and Biomedicine, en memoria del Profesor Julio Rodríguez Villanueva, celebrado en Madrid (España), los días 23 y 24 de enero de 2020Rts1 is the regulatory subunit of protein phosphatase 2A, sharing an overall identity of 47% with S. cerevisiae Rts1, although it contains an insert of around 100 amino acids located within the B56 regulatory domain, not present in ScRts1 was common in other fungal homologs, suggesting that they might have diverged from its S. cerevisiae counterpart to fulfil specific functions in the regulation of the PP2A phosphatase

Nucleotide sequence of a 1, 3–1, 4-β-glucanase-encoding gene in Bacillus circulans WL-12

This research was supported by a grant from CAICYT (project A-121).Peer reviewe