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Molecular Genetics

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The long-range interest of the laboratory is in the epidemiology, genetics, evolutionary and biochemical mechanisms of antibiotic resistant pathogens, specifically, staphylococci, Streptococcus pneumoniae, and enterococci..

 

 


Hermínia de Lencastre
Professor Catedrático
PhD in Biology 1981 Universidade Nova de Lisboa 

Phone (+351) 214469860
hml@itqb.unl.pt

  

Research Interests

The emergence and spread of antibiotic resistant clones of Staphylococcus spp., and Streptococcus pneumoniae pose a public health threat worldwide. The phenomenon also presents fascinating problems of basic science, such as the evolutionary origin of resistance genes; the mechanism of antibiotic resistance and the question of what combination of determinants provides the epidemic “success” of these pathogens. Our laboratory is actively involved both in the public health related and also in the biological aspects of this problem.

Methicillin-resistant Staphylococcus aureus (MRSA) are a major cause of nosocomial infections worldwide and have emerged recently in the healthy community, posing a public health concern. We aim to characterize the molecular epidemiology of MRSA in hospitals and in the community and to track the evolutionary origin and spread of the ß-lactam resistance gene. Other staphylococcal species are also under study as they are thought to be important reservoirs and key players in the evolution of ß-lactam resistance determinants.

Moreover, we investigate the molecular mechanisms leading to ß -lactam resistance in MRSA, namely through the study of the biosynthetic steps of peptidoglycan, a major cell wall component and target of these antibiotics. Several approaches are used, including the biochemical characterization of cell wall mutants, studies on gene expression regulation and protein interactions.

S. pneumoniae remains a leading cause of morbidity and mortality worldwide causing a wide range of infectious diseases. Its sole ecological niche is the human nasopharynx and children of preschool age their major reservoir. Our laboratory has been engaged since 1996 in extensive studies aimed to better understand the nasopharyngeal ecosystem and how it is affected by interventions such as antibiotic use and vaccines. Since 2011 our work on Pneumo has been carried out in collaboration with Dr. Raquel Sá-Leão Laboratory.

Our research is done in collaboration with Portuguese and foreign scientists worldwide through CEM/NET and other initiatives and is supported by the European Community, Fundação Para a Ciência e Tecnologia and Fundação Calouste Gulbenkian.

 

Group Members

  • Alexander Tomasz, Ph.D Adjunct Full Professor
  • Ana Ludovice, Assist. Prof. FCT/UNL
  • Rita G. Sobral, Auxiliary Investigator, CREM;/FCT/UNL
  • Susana Gardete, Ph.D.*, Post-Doc
  • Catarina Milheiriço, Ph.D., Post-Doc
  • Teresa Conceição, Ph.D., Post-Doc
  • Nelson Frazão, Ph.D., Post-Doc
  • Teresa Figueiredo, PhD student
  • Ana Tavares, PhD student
  • Inês Grilo, PhD student
  • Celine Coelho, Research student
  • Raquel Portela, Graduate student
  • Isilda Gueifão, Technician
  • Anastásiya Havrysh, Technician Trainee
  • Manuela Nogueira, Administrative Assistant

*currently at The Rockefeller University
 

Selected Publications

  1. Arêde, P., C. Milheiriço , H. de Lencastre, and D. C. Oliveira. 2012. The anti-repressor MecR2 promotes the proteolysis of the mecA repressor and enables optimal expression of -lactam resistance in MRSA. PLoS Pathogens 8:e1002816.
  2. Figueiredo, T.A., R. G. Sobral, A. M. Ludovice, J. M. F. de Almeida, N. K. Bui, W. Vollmer, H. de Lencastre and A. Tomasz. 2012. Identification of genetic determinants and enzymes involved with the amidation of glutamic acid residues in the peptidoglycan of Staphylococcus aureus. PLoS Pathogens. 8:e1002508.
  3. Harris, S., E. J. Feil, M. T.G. Holden, M. A. Quail, E. K. Nickerson, N. Chantratita, S. Gardete, A. Tavares, N. Day, J. Lindsay, J. Edgeworth, H. de Lencastre, J. Parkhill, S. J. Peacock, and S. D. Bentley. 2010. Evolution of MRSA during hospital transmission and intercontinental spread. Science 327:469-74.

 

Laboratory's Website

For further information visit the laboratory's website

 

Genética Molecular (PT)

Um dos principais objectivos do nosso laboratório foca o estudo do mecanismo de resistência aos antibióticos ß-lactâmicos em Staphylococcus aureus, cujo elemento central é o gene exógeno mecA. Pretendemos responder a duas questões importantes em biologia evolutiva, nomeadamente o(s) mecanismos(s) de aquisição do gene mecA pela bactéria hospedeira e como é que este gene proporciona um fenótipo de resistência.

Outro objectivo é caracterizar, por métodos de epidemiologia molecular e por sequenciação completa do genoma, a estrutura populacional de bactérias patogénicas - Staphylococcus aureus, e os estafilococos coagulase negativos, responsáveis por um elevado número de infecções em hospitais e na comunidade em todo o mundo, constituindo uma causa importante de morbilidade e mortalidade. Pretendemos ainda, pela caracterização molecular de estirpes provenientes destes dois ambientes, estabelecer ligações epidemiológicas entre eles e compreender os mecanismos moleculares da sua evolução.

 

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