SMANIA, Andrea

Independent Researcher CONICET / Associate Professor UNC
Phone: +54 351 5353855 int 3452
E-mail: andream.smania@gmail.com; asmania@fcq.unc.edu.ar

Research Topic

Mutating for survival: Adaptive mutagenic mechanisms of adaptive in the opportunistic pathogen Pseudomonas aeruginosa

Pseudomonas aeruginosa, is a bacterial species with a remarkable genetic and metabolic versatility that allow it to proliferate in many different and diverse habitats, including the human body, where it constitutes an important opportunistic pathogen as the etiologic agent of a wide variety of infections and the main cause of chronic airway infections and mortality in patients with cystic fibrosis (CF).
Our interest focuses on understanding the molecular basis underlying the great adaptive capability of P. aeruginosa, and this prompted us to the study of different systems or factors by which cells can increase the mutation rate and acquire hypermutator states. The mechanisms that bacteria use to increase the mutation rate are those that we refer to as mutagenic mechanisms, and include: (i) stable hypermutability, which involves those systems that are responsible for preventing or repairing DNA lesions, being the Mismatch Repair System the paradigm; (ii) transient hypermutability, which involves stress response systems that regulate the action of different error prone DNA polymerases, such as PolIV; (iii) and localized hypermutability, in which intrinsic properties of the DNA sequence cause the raise of mutation rate particularly in this sequence, thus localizing the mutability only in a region of the genome that becomes a hot spot for mutation. During our investigations, we have been trying mainly to unravel the question of how does P. aeruginosa acquire those mutations that lead to particular phenotypic switches, focusing on adaptive ones, such as mucoid conversion, the emergence of quorum sensing altered variants and small colony variants, all hallmarks of P. aeruginosa infections in CF. These investigations have led us to lately inquire about the involvement of hypermutability on more complex phenotypic diversification processes, such as biofilm formation, or those that P. aeruginosa suffers during chronic airway infections.

Selected publications

• Coexistence and within-host evolution of diversified lineages of hypermutable Pseudomonas aeruginosa in long-term cystic fibrosis infections. Feliziani S, Marvig RL, Luján AM, AJ Moyano, Di Rienzo JA, Krogh Johansen H, Molin S, Smania AM. PLoS Genet. 2014 Oct 16;10(10):e1004651.
• A long-chain flavodoxin protects Pseudomonas aeruginosa from oxidative stress and host bacterial clearance. AJ Moyano, Tobares RA, Rizzi YS, Krapp AR, He said JA, JL Bocco, Saleh MC, Carrillo N, Smania AM. PLoS Genet. 2014 Feb 13;10(2):e1004163.
• Evolution and adaptation in Pseudomonas aeruginosa biofilms driven by mismatch repair system-deficient mutators. Luján AM, Maciá MD, Yang L, Molin S, Oliver A, Smania AM. PLoS One. 2011;6(11):e27842.
• Mucoidy, quorum sensing, mismatch repair and antibiotic resistance in Pseudomonas aeruginosa from cystic fibrosis chronic airways infections. Feliziani S, Luján AM, AJ Moyano, Sola C, JL Bocco, Montanaro P, Canigia LF, EC Argaraña, Smania AM. PLoS One. 2010 Sep 10;5(9). pii: e12669.
• 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. AJ Moyano, Luján AM, EC Argaraña, Smania AM. Mol Microbiol. 2007 Apr;64(2):547-59.

(See more publications-CONICET)

Researchers members of the group

• Alejandro Moyano – Adjunct Researcher-National Council of Scientific and Technological Research (CONICET)

Fellows

• Adela Lujan -Marie Curie Postdoctoral Fellow (Return Phase)
• Antonella Colque-CONICET Fellow
• Laura Hedeman-CONICET Fellow

Current Grants

• Mutating for survival: adaptive mutagenic mechanisms of mutagenesis in the opportunistic pathogen P. aeruginosa”” granted by the National Agency for Scientific and Technological Promotion. PICT2012-2088, from 2013 to 2016. Awarded amount: $ 322,200.
• Comparative analysis of the adaptability of bacteria from Pseudomonas genus: microaerobic and oxidative stress granted by the National Council of Scientific and Technological Research (CONICET) PIP-2013, from 2015 to 2017. Awarded amount: $ 295,000

Brief CV

Academic Formation

• Doctorate of Philosophy – Biological Sciences (1990-1995). Center of Research in Biological Chemistry of Cordoba (CIQUIBIC-CONICET) and Department of Biological Chemistry, Chemistry Sciences School, National University of Córdoba, Argentina. Outstanding (10/10)
• Biologist (1985-1990), Natural Sciences School, National University of Cordoba. Outstanding (9.14/10)
  Research Background

Relevant Positions

• Independent Researcher of the National Council for Scientific and Technical Research (CONICET, Argentina) (2012-today). Center of Research in Biological Chemistry of Cordoba (CIQUIBIC-CONICET) and Department of Biological Chemistry, Chemistry Sciences School, National University of Córdoba, Argentina.
• Adjunct Researcher of CONICET, Argentina) (2005-2012). Center of Research in Biological Chemistry of Cordoba (CIQUIBIC-CONICET) and Department of Biological Chemistry, Chemistry Sciences School, National University of Córdoba, Argentina.
• Assistant Researcher of CONICET (2000-2005). Center of Research in Biological Chemistry of Cordoba (CIQUIBIC-CONICET) and Department of Biological Chemistry, Chemistry Sciences School, National University of Córdoba, Argentina.
• Post-doctoral Researcher (1999) Laboratory of Molecular and Environmental Microbiology, Systems and Synthetic Biology Program, National Center for Biotechnology, Superior Council of Scientific Investigations (CNB-CSIC), Madrid, Spain. Under the supervision of Prof. Victor de Lorenzo.

Relevant Awards

• Award for Basic Sciences Research of the national Academy of Medicine (2010) “Implications of the mechanisms of mutagenesis in the emergence of adaptive phenotypes of P. aeruginosa.”
  Cystic Fibrosis Foundation Award 2006 “P. aeruginosa leading cause of chronic lung infections in patients with Cystic Fibrosis. Studies of the relationship between hypermutability and mucoid conversion”

Scientific meetings and conferences

• International: 15
• Domestic: 43
• Invited speaker in 8 international meetings and seminars
• Invited speaker in 12 domestic meetings, conferences and seminars

Collaborators

• Nestor Carrillo, Institute of Molecular and Cell Biology of Rosario (IBR-CONICET), Argentina
• Soren Molin, Department of System Biology Technical University of Denmark (DTU), Denmark

Affiliations

• Member of the Society for Research in Biochemistry and Molecular Biology (REVIEW, Argentina), Society for General Microbiology (SAMIGE, Argentina), American Society for Microbiology (ASM, USA) and the International Society for Microbial Ecology (ISMA).

Teaching Background
Relevant positions

• Associate Professor (2014-today). Department of Biological Chemistry, Chemistry Sciences School, UNC, Argentina.
• Adjunct Professor (2008-2014). Department of Biological Chemistry, Chemistry Sciences School, UNC, Argentina.
• Assistant Professor (1990-2008). Department of Biological Chemistry, Chemistry Sciences School, UNC, Argentina.

Teaching experience

• Professor in advanced undergraduate courses and graduate courses in the Chemical Sciences School, UNC.
• Invited Professor in graduate courses in different national Universities, Argentina

Institutional Management Background

• Vice Director of the Department of Biological Chemistry, Chemistry Sciences School, National University of Córdoba, (2015-today)
• Member of the Board of CIQUIBIC-CONICET, Chemistry Sciences School, National University of Córdoba. (2013-today)
• Member of the Board of the Department of Biological Chemistry, Chemistry Sciences School, National University of Córdoba (2013-2015)
• Member of different Committees in the Chemistry Sciences School, National University of Córdoba (1998-2014)
• Member of the Board of the Chemistry Sciences School, National University of Córdoba. (1998-2000)
• Member of the Board of the Department of Biological Chemistry, Chemistry Sciences School, National University of Córdoba (1994-1996)

Background on Science outreach and extension

• General coordinator in the Week of Science and Technology, organized by the National Ministry of Science and Technology and the FCQ, UNC (2003-2012)
• Director of extension project “Hypermutability as adaptive strategy in P. aeruginosa. Study of hypermutable strains in a Cordoba CF population“ Collaborator: Children’s Hospital of Cordoba. Code 1505B07 Awarded amount: 4400$ (2008)

Invited speaker in Popular Science Events

• “Chemistry Research” organized by the Center of Students of the FCQ, UNC. May 2014
• “Chemistry between us” organized by the FCQ, UNC in the International Year of Chemistry. November 2011
• Interdisciplinary Congress of Health Sciences Students, organized by the Ministry of Education and the UNC, on occasion of the visit of the Nobel Prize in Chemistry 2009 Thomas STEITZ. October 2011
• Conference on Education, Informative Care and Treatment of Cystic Fibrosis, organized by the Foundation for Child Welfare Assistance Program in Cystic Fibrosis. November 2010

Directed Ph.D. Theses

• Alejandro Moyano. PhD in Chemistry, Chemical Sciences School, National University of Cordoba. “Role of the mechanisms of mutagenesis in mucoid conversion in Pseudomonas aeruginosa” December 2009.
• Adela Lujan, PhD in Chemistry, Chemical Sciences School, National University of Cordoba. “Mechanisms of mutagenesis, lasR phenotype conversion and biofilm formation in Pseudomonas aeruginosa” October 2011.
• Sofia Feliziani, PhD in Chemistry, Chemical Sciences School, National University of Cordoba. “Genomic evolution of hypermutable Pseudomonas aeruginosa populations in chronic lung infections in patients with cystic fibrosis” March 2014.