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Genética Molecular de la Patogénesis Fúngica Genética Molecular de la Patogénesis Fúngica
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M. Isabel González Roncero
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Antonio Di Pietro
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Signalling and pathogenesis in fungi
Responsible: Antonio Di Pietro

Fungal pathogens use chemical and physical signals to sense nutrient status, surface contact and presence of the host. This information is processed by a network of conserved cellular pathways and leads to the activation of the genetic infection program. One of the key pathways is the so-called Pathogenicity MAPK (Mitogen-Activated Protein Kinase) cascade, which is orthologous to the mating and filamentation MAPK cascade in Saccharomyces cerevisiae, and is strictly requited for virulence in a wide range of plant pathogenic fungi. Our group was the first to characterize the Pathogenicity MAPK (named Fmk1 for Fusarium MAP Kinase 1) in a soilborne plant pathogen. Mutants of F. oxysporum lacking Fmk1 are deficient in penetration of tomato roots and fail to cause disease on plants, but show normal growth on rich media. A major effort in our lab is directed towards understanding the specific role of this conserved MAPK cascade in fungal pathogenicity. Previous work established that Fmk1 controls multiple virulence-related processes such as adhesion to host surfaces, production of cell wall-degrading enzymes, invasive growth on the host tissue and vegetative hyphal fusion.

Extracellular signals and chemotropic response in F. oxysporum
 

In spite of the highly conserved role of the Pathogenicity MAPK cascade, virtually nothing is known about the signals and receptors that regulate this pathway. One of the earliest responses of fungal pathogens during infection is the perception of extracellular cues from the host, followed by chemotropic hyphal growth towards the stimulus. To unravel the molecular mechanisms of chemotropism in F. oxysporum, we have developed a rapid and reproducible assay for quantification of chemotropic growth in fungal germlings. Our results indicate that F. oxysporum can sense and grow towards a variety of chemical stimuli such as nutrients, pheromones or host signals. We have recently initiated the characterization of the receptors and cellular pathways that are involved in perception of the extracellular signals and in their transduction to activate the chemotropic response. We are working on the characterization of the signals and their cognate receptors, as well as the cellular pathways involved in their perception and transduction to activate the chemotropic response.

Role of the transmembrane mucin Msb2 in MAPK signalling and virulence
 

In S. cerevisiae, the transmembrane protein Msb2 functions upstream of Kss1, the MAPK orthologous to Fmk1. We have identified the msb2 gene encoding an integral membrane protein of F. oxysporum with similar domain architecture to yeast Msb2, including a highly O-glycosylated extracellular domain characteristic of the mucin protein family and a short cytoplasmic tail. Deletion of msb2 leads to reduced levels of phosphorylation of Fmk1, suggesting that Msb2 functions upstream of the Pathogenicity MAPK. Msb2 is expressed during tomato root infection, and Δmsb2 mutants are reduced in invasive growth and virulence on tomato plants. A second membrane protein, Sho1, regulates the same downstream processes in combination with Msb2. Our current research addresses two key questions regarding the role of Msb2 and Sho1 in signalling and virulence: what are the signals and mechanisms for their activation and what are the interaction partners that mediate the downstream responses?

Identification of a conserved nitrogen response pathway regulating fungal virulence
 

Nitrogen limitation appears to act as a key signal for the activation of virulence functions in plant pathogens. We set out to explore a possible crosstalk between nitrogen response signalling and the Fmk1 MAPK cascade in the control of pathogenicity of F. oxysporum. The preferred nitrogen source ammonium was found to repress virulence-related functions that depend on the Fmk1 MAPK such as cellophane penetration, vegetative hyphal fusion and root adhesion. Tomato plants supplied with ammonium rather than nitrate showed a significant delay in the development of vascular wilt disease caused by F. oxysporum. Ammonium repression could be reversed by rapamycin, a specific inhibitor of the TOR kinase that orchestrates eukaryotic cell growth in response to nutrient availability. We also discovered that MeaB, a bZIP protein known to mediate nitrogen catabolite repression in Aspergillus, is required for ammonium-mediated repression of virulence functions. Intriguingly, the repressing effect of ammonium on invasive growth is also functional in the rice blast fungus M. oryzae and the wheat head blight fungus F. graminearum, suggesting that it may be broadly conserved in plant pathogens. Our next goals are to identify additional components of the nitrogen response pathway and to understand, how it interacts with the pathogenicity MAPK cascade to regulate virulence in plant pathogenic fungi.

Transcriptional programs regulating fungal infection on plants and mammals
 

F. oxysporum causes disease both on plants and mammals. Today, it is the only model reported in fungi that allows to compare infection mechanisms on the two classes of hosts. Using forward and reverse genetics we have identified a number of genes required for virulence of F. oxysporum on tomato and/or on immunodepressed mice. We are applying massive sequencing (RNAseq) to elucidate the transcriptional programs that are triggered during the process of infection on plant and mammalian hosts.

  Señalización y patogénesis en hongos
 
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