Participation of Candida albicans transcription factor RLM1 in cell wall biogenesis and virulence.
Candida albicans cell wall is important for growth and interaction with the environment. RLM1 is one of the putative transcription factors involved in the cell wall integrity pathway, which plays an important role in the maintenance of the cell wall integrity. In this work we investigated the involvement of RLM1 in the cell wall biogenesis and in virulence. Newly constructed C. albicans Δ/Δrlm1 mutants showed typical cell wall weakening phenotypes, such as hypersensitivity to Congo Red, Calcofluor White, and caspofungin (phenotype reverted in the presence of sorbitol), confirming the involvement of RLM1 in the cell wall integrity. Additionally, the cell wall of C. albicans Δ/Δrlm1 showed a significant increase in chitin (213%) and reduction in mannans (60%), in comparison with the wild-type, results that are consistent with cell wall remodelling. Microarray analysis in the absence of any stress showed that deletion of RLM1 in C. albicans significantly down-regulated genes involved in carbohydrate catabolism such as DAK2, GLK4, NHT1 and TPS1, up-regulated genes involved in the utilization of alternative carbon sources, like AGP2, SOU1, SAP6, CIT1 or GAL4, and genes involved in cell adhesion like ECE1, ALS1, ALS3, HWP1 or RBT1. In agreement with the microarray results adhesion assays showed an increased amount of adhering cells and total biomass in the mutant strain, in comparison with the wild-type. C. albicans mutant Δ/Δrlm1 strain was also found to be less virulent than the wild-type and complemented strains in the murine model of disseminated candidiasis. Overall, we showed that in the absence of RLM1 the modifications in the cell wall composition alter yeast interaction with the environment, with consequences in adhesion ability and virulence. The gene expression findings suggest that this gene participates in the cell wall biogenesis, with the mutant rearranging its metabolic pathways to allow the use of alternative carbon sources.
Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, Braga, Portugal.
Yolanda
Y
Delgado-Silva
Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, Braga, Portugal.
Catarina
C
Vaz
Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, Braga, Portugal.
Joana
J
Carvalho-Pereira
Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, Braga, Portugal.
Catarina
C
Carneiro
Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, Braga, Portugal.
Eugénia
E
Nogueira
Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, Braga, Portugal ; Departamento de Imuno- Fisiologia e Farmacologia, ICBAS-UP - Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Porto, Portugal.
Alexandra
A
Correia
RNA Biology Laboratory, Department of Biology and CESAM, University of Aveiro, Portugal.
Laura
L
Carreto
Institute for Biotechnology and Bioengineering, Centre of Biological Engineering, University of Minho, Braga, Portugal.
Sónia
S
Silva
Departamento de Imuno- Fisiologia e Farmacologia, ICBAS-UP - Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Porto, Portugal ; Departamento de Patologia e Imunologia Molecular, ICBAS- UP, Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Porto, Portugal.
Augusto
A
Faustino
Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, Braga, Portugal.
Célia
C
Pais
Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, Braga, Portugal.
Rui
R
Oliveira
Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, Braga, Portugal.
Paula
P
Sampaio
D000818:Animals; D002176:Candida albicans / Q000378:metabolism* / Q000472:pathogenicity; D058387:Candidemia / Q000382:microbiology*; D002473:Cell Wall / Q000378:metabolism*; D005260:Female; D005656:Fungal Proteins / Q000502:physiology*; D015966:Gene Expression Regulation, Fungal; D007668:Kidney / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D014157:Transcription Factors / Q000502:physiology*; D059467:Transcriptome; D014774:Virulence
D005656:Fungal Proteins; D014157:Transcription Factors