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MOYANO, Alejandro

Associate Researcher CONICET
E-mail: amoyano@fcq.unc.edu.ar

Research topic

Role of the different allelic variants MucA global regulator in the opportunistic pathogen Pseudomonas aeruginosa

During the establishment of chronic infection, Pseudomonas aeruginosa undergoes a transformative process based on the acquisition of mutations in specific genes and consequent diversification allows the emergence of phenotypes suitable for different micro-niche generated in the heterogeneous environment lung cystic fibrosis patients. Of all phenotypes that can be found in these chronic infections, no doubt that concentrated most attention is clinically mucoid phenotype (overproducer variant exopolysaccharide alginate), since the appearance of these variants is a sign of irreversibility of infection and has a poor prognosis for the patient fibrocystic. Because of this, mucoid phenotype for decades was a primary subject of study in an attempt to understand and combat chronic infections caused by P. aeruginosa. Without a doubt, over the years great strides aimed at the characterization and elucidation of metabolic pathways were conducted, as well as genetic and regulatory aspects related to this phenotype. Numerous studies showed that the most frequent cause of conversion to the mucoid phenotype, are mutations that cause loss of function in the mucA gene, a major negative regulators of alginate production. Under normal physiological conditions, MucA fulfills its function as a negative regulator of alginate synthesis abduct alternative sigma factor σ22, encoded by the gene ALGT, and suppress its activity. ALGT exerts its positive regulation by binding to the promoter region of algD, the first gene biosynthetic operon, which catalyzes the first step in the synthesis of alginate. In this way, for decades the role of mutations in mucA was inexorably associated with the effect that they conferred on their ability to regulate ALGT. Therefore, The overall objective of this project is to explore the effect of mutations in the global regulator MucA of opportunistic pathogenic species P. aeruginosa regarding the alteration of the transcriptional regulatory properties and, and contribute to the understanding of the molecular mechanisms involved in versatility P. aeruginosa the adaptation processes to different environmental conditions, such as those occurring in the setting of chronic lung infections in patients with cystic fibrosis.

Selected Publications

Brief Curriculum Vitae

  • Doctor in Chemistry - Faculty of Chemistry, Universidad Nacional de Córdoba. 17 December 2009. Qualification: Outstanding.
  • Biologist - Faculty of Sciences, Physical and Natural; Universidad Nacional de Córdoba. 5 March 2002. Average c / aplazos: 8.15 Average s / aplazos: 8.32

  • Moyano. J., Tobares R. A., Rizzi Y. S., Krapp A., he said J. A., Bocco J. L., Saleh M-C., Carrillo N. & A. M. Craving. 2014. “A long-chain flavodoxin protects Pseudomonas aeruginosa from oxidative stress and host bacterial clearance”. PLoS Genet. 10: e1004163.
  • Feliziani S., Marvig R. L., Lujan. M., Moyano. J., Di Rienzo J. A., Johansen H. K., Molin S. & A. M. Craving. 2014. “Coexistence and within-host evolution of diversified linages of hypermutable Pseudomonas aeruginosa in long-term cystic fibrosis infections”. PLoS Genet. 10: e1004651.
  • Moyano. J., Feliziani S., Di Rienzo J. A. & A. M. Craving. 2013. “Simple sequence repeats together with mismatch repair deficiency can bias mutagenic pathways in Pseudomonas aerugiosa during chronic lung infection”. PLoS ONE 8: e80514.
  • Sola C., Paganini H., Egea. L., Moyano. J., Garnero A., Kevric I., Culasso C., Vindel A., Study Group of CA-MRSA in Children, Argentina-2007, Lopardo H. & J. L. Bocco. 2012. “Spread of epidemic MRSA-ST5-IV clone encoding PVL as a major cause of community onset staphylococcal infections in Argentinean children”. PLoS ONE 7: e30487.
  • Feliziani S., Lujan. M. *, Moyano. J. *, Sola C., Bocco J. L., Montanaro P., Caniggia L. Fernández, Argarana C. E. & A. M. Craving. 2010. “Mucoidy, quorum sensing, mismatch repair and antibiotic resistance in Pseudomonas aeruginosa from cystic fibrosis chronic airways infections”. PLoS ONE 5: e12669. * equivalent contribution.
  • Moyano. J. & A. M. Craving. 2009. “Simple sequence repeats and mucoid conversion: biased mucA mutagenesis in mismatch repair-deficient Pseudomonas aeruginosa”. PLoS ONE 4: e8203.
  • Moyano. J., Lujan. M., Argarana C. E. & A. M. Craving. 2007. “MutS deficiency and activity of the error-prone DNA Polymerase IV are crucial for determining mucA as the main target for mucoid conversion in Pseudomonas aeruginosa”. Mol. Microbiol. 64: 547-559.
  • Lujan. M., Moyano. J., Safe I., Argarana C. E. & A. M. Craving. 2007. “Quorum sensing deficient (LASR) mutants emerge at high frecuency from a Pseudomonas aeruginosa mutS strain”. Microbiology (SGM) 153: 225-237.
  • Moyano. J. & G. M. Daniele. 2003. "New record Psilocybe (Fungi, Basidiomycotina, Agaricales) in Argentina". Acta Bot. Mex. 64: 25-29.

  • 2010. "Basic Research 2010" the best research "Mechanisms of Mutagenesis Implication in the emergence of Phenotypes Adaptive Award Pseudomonas aeruginosa". Moyano. J., Lujan. M., Feliziani S., Argarana C. E. & A. M. Craving. Awarded by the Academy of Medical Sciences.
  • 2006. "FOUNDATION-F.Q." The second best research "awardPseudomonas aeruginosa, leading cause of chronic lung infections in patients with CF.: Studies of the relationship between hypermutability and conversion to mucoid phenotype ". Moyano. J., Lujan. M., Argarana C. E. & A. M. Craving. Awarded by the Foundation for Child Welfare - Assistance Program Cystic Fibrosis.

Research Topic

Role of the different allelic variants of MucA in the opportunistic pathogen Pseudomonas aeruginosa

During the establishment of chronic infection, Pseudomonas aeruginosa undergoes a transformative process based on the acquisition of mutations in specific genes. This allows the emergence of phenotypes suitable for different micro-niches generated in the heterogeneous environment of the lung of patients with cystic fibrosis. Of all phenotypes, undoubtedly, the mucoid phenotype (overproducer of the exopolysaccharide alginate) concentrated most of the clinical attention, since the appearance of these variants constitutes a sign of irreversibility of the infection and poor prognosis for the patient. Because of this, for decades the mucoid phenotype was a primary object of study in the attempt to understand and combat chronic infections caused by P. aeruginosa. Over the last years, great steps were achieved towards the characterization and elucidation of metabolic pathways, as well as genetic and regulatory aspects related to this phenotype. Numerous studies showed that the most frequent source of mucoid conversion, are mutations that cause loss of function in the mucA gene, one of the major negative regulators of alginate production. Under normal physiological conditions, MucA fulfills its function by kidnaping the alternative sigma factor σ22 (encoded by algT), thereby suppressing its positive regulation. When AlgT is released, it binds to the promoter region of algD, the first gene of the biosynthetic operon, which catalyzes the first step in the synthesis of alginate. In this context, the overall objective of this project is to explore the effect of different mucA mutations on the alteration of transcriptional and regulatory properties of opportunistic pathogen P. aeruginosa. Findings in this area will help to understand the molecular mechanisms involved in the versatility of P. aeruginosa in the adaptive processes to different environmental conditions, such as those occurring in the establishment of chronic lung infections in patients with cystic fibrosis.

Selected Publications

(See more publications-CONICET)

Current Grants

  • 2014-2016. National Agency for Scientific and Technological Promotion (ANPCYT) – PICT-2013-3180
  • 2014-2016. National Council of Scientific and Technical Research (CONICET) – PIP

Brief CV

Academic Formation

  • 2009-Ph.D. in Chemical Sciences – College of Chemical Sciences – National Univeristy of Cordoba.
  • 2002-Biologist – College of Natural Sciences – National University of Córdoba.

Research Background

Present position

  • Research Career member of CONICET at CIQUIBIC – CONICET; Dept. of Biological Chemistry – College of Chemical Sciences, National Univeristy of Cordoba.

Past positions

  • 2010 – 2013. Postdoctoral position at CIBICI – CONICET, Dept. of Clinical Biochemistry – College of Chemical Sciences, National Univeristy of Cordoba, under the supervision of Dr. José L. Bocco.

Teaching Background

  • Teaching stuff with more than 13 years of experience at the Dept. Biological Chemistry, College of Chemical Sciences, National Univeristy of Cordoba.

Undergraduate courses

  • Biotechnology, Biological Chemistry, Molecular and Cell Biology, Macromolecule Biochemistry.