Jesus Pla

Director:

Jesús Pla, Ph.D., Professor of Microbiology

E-mail: jesuspla@farm.ucm.es
 Tel: (+34) 91 394 1617

Lab Members:

Rebeca Alonso Monge, Ph.D. Assistant Professor (realonso@farm.ucm.es)

Elvira Román, Ph.D. (elvirarg@farm.ucm.es)

Daniel Prieto, Ph.D. Student

(adprietorg@farm.ucm.es)

Carmen Herrero, Ph.D. Student

(cmherrero@gmail.com)

Inés Correia, Ph.D. Student

(ainescorreia351@gmail.com)

Blanca Huertas, Ph.D. Student (blanca.huertas86@gmail.com)

Carla Dias, ERASMUS Student. U. Coimbra, Portugal

National Institutes of HealthNational Institute of Health, 2005-2011.
Community of Madrid Comunidad Autónoma de Madrid (C.A.M.), 2004-2010.

Phagocyted C. albicans cellsResearch Line:

Signal Transduction and Immune Response in Human Pathogenic Fungi

Our group is involved in the analysis of host-pathogen interactions during fungal infection. We mainly use Candida albicans as model organism to explore fungal pathogenesis. C. albicans is a dimorphic yeast that frequently inhabits the gastrointestinal and vaginal tract in humans; however, under circumstances that result in impaired host immunological responses (such as those that result from HIV infection or treatment with immune suppressors) it is able to gain access to different target organs and generate diseases collectively called candisiasis. It is therefore, an opportunistic fungal pathogen and probably the best established model of fungal pathogenesis.

Our work mainly focuses on the role that MAP kinase signal transduction pathways play in this microbe; these cascades rely on phosphorylation for the transmission of an environmental-generated signal to the nucleus where a transcriptional response is developed allowing adaptation to the new conditions.  We are interested determining the specificity of the stimuli, theresponses generated and the interactions among these routes. We want to determine the consequences of their activation, with special emphasis in their role in cell wall biosynthesis and dimorphism, as both processes are essential to the cell. A better understanding of this complex system may be exploited for the design of new and novel antifungals.

Experimental approaches and methodologies used in our research comprise molecular genetics, biochemistry, cell biology, genome wide strategies (transcriptomal and proteomic) and experimental infection in mice.

Recently, we are using genetically modified strains disrupted in genes essential to pathogenesis to understand the mechanisms used by the immune system to control Candida infections. We are determining the key components (receptors and/or cytokines) that influence the decision of the host towards control (commensalism) or susceptibility to invasion (disease). In particular, we are paying attention to the role of dendritic cells and neutrophils as key cells that determine influence antigen presentation and cell killing (respectively) and therefore progression or control of the disease. We are also using model of commensalism in mice to define the role of certain host specific genes in susceptiblity to infection.

An envisioned short term goal of our group in to develop tools, strategies and methodologies to image in vivo a fungal infection.

Recent publications

  1. Ernst,J.F. and Pla,J. (2011) Signaling the glycoshield: maintenance of the Candida albicans cell wall. Int. J. Med. Microbiol. 301, 378-383.
  2. R. Alonso-Monge et al.,The Sko1 protein represses the yeast-to-hypha transition and regulates the oxidative stress response in Candida albicans Fungal. Genet. Biol. 47, 587 (2010).
  3. D. M. Arana, C. Nombela, J. Pla,Fluconazole at subinhibitory concentrations induces the oxidative- and nitrosative-responsive genes TRR1, GRE2 and YHB1, and enhances the resistance of Candida albicans to phagocytes J. Antimicrob. Chemother. 65, 54 (2010).
  4. I. Correia, R. Alonso-Monge, J. Pla,MAPK cell-cycle regulation in Saccharomyces cerevisiae and Candida albicans Future. Microbiol. 5, 1125 (2010).
  5. C. H. de Dios, E. Roman, R. A. Monge, J. Pla,The role of MAPK signal transduction pathways in the response to oxidative stress in the fungal pathogen Candida albicans: implications in virulence Curr. Protein Pept. Sci. 11, 693 (2010).
  6. M. Galan-Diez et al.,Candida albicans beta-glucan exposure is controlled by the fungal CEK1-mediated mitogen-activated protein kinase pathway that modulates immune responses triggered through dectin-1 Infect. Immun. 78, 1426 (2010).
  7. P. Gonzalez-Parraga, R. Alonso-Monge, J. Pla, J. C. Arguelles,Adaptive tolerance to oxidative stress and the induction of antioxidant enzymatic activities in Candida albicans are independent of the Hog1 and Cap1-mediated pathways FEMS Yeast Res.  10, 747 (2010).
  8. R. Alonso-Monge, S. Carvaihlo, C. Nombela, E. Rial, J. Pla,The Hog1 MAP kinase controls respiratory metabolism in the fungal pathogen Candida albicans Microbiol. 155, 413 (2009).
  9. R. Alonso-Monge, E. Román, D. M. Arana, J. Pla, C. Nombela,Fungi sensing environmental stress Clin. Microbiol. Infect. 15 Suppl 1, 17 (2009).
  10. Alonso-Monge, E. Román, J. Pla, C. Nombela, in Evolutionary biology of bacterial and fungal pathogens, F. Baquero Mochales, C. Nombela, G. H. Cassel, J. A. Gutiérrez-Fuentes, Eds. (ASM Press, Washington, D.C., 2009) ,chap. 11, pp. 105-115.
  11. D. M. Arana et al.,The role of the cell wall in fungal pathogenesis Microb. Biotechnol. 2, 308 (2009).
  12. Fungi sensing environmental stress., Alonso-Monge R, Román E, Arana DM, Pla J, Nombela C., Clin Microbiol Infect.2009 Jan;15 Suppl 1:17-9. Review. PMID: 19220347
  13. The Hog1 MAP kinase controls respiratory metabolism in the fungal pathogen Candida albicans. Alonso-Monge R, Carvaihlo S, Nombela C, Rial E, Pla J. Microbiology. 2009 Feb;155(Pt 2):413-23. PMID: 19202089
  14. Transcriptional and physiological adaptation to defective protein-O-mannosylation in Candida albicans. Cantero PD, Lengsfeld C, Prill SK, Subanović M, Román E, Pla J, Ernst JF. Mol Microbiol. 2007 May;64(4):1115-28. PMID: 17501932
  15. Differential susceptibility of mitogen-activated protein kinase pathway mutants to oxidative-mediated killing by phagocytes in the fungal pathogen Candida albicans. Arana DM, Alonso-Monge R, Du C, Calderone R, Pla J. Cell Microbiol. 2007 Jul;9(7):1647-59. Epub 2007 May 8. PMID: 17346314
  16. MAP kinase pathways as regulators of fungal virulence. Román E, Arana DM, Nombela C, Alonso-Monge R, Pla J. Trends Microbiol. 2007 Apr;15(4):181-90. Epub 2007 Feb 23. Review. PMID: 17321137
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