Associate Researcher CONICET
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.
- 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.
- 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.
- 2014-2016. National Agency for Scientific and Technological Promotion (ANPCYT) – PICT-2013-3180
- 2014-2016. National Council of Scientific and Technical Research (CONICET) – PIP
- 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 Career member of CONICET at CIQUIBIC – CONICET; Dept. of Biological Chemistry – College of Chemical Sciences, National Univeristy of Cordoba.
- 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 stuff with more than 13 years of experience at the Dept. Biological Chemistry, College of Chemical Sciences, National Univeristy of Cordoba.
- Biotechnology, Biological Chemistry, Molecular and Cell Biology, Macromolecule Biochemistry.