1990–1995: BSc/MSc in Applied Chemistry/Biotechnology, FCT/UNL, Monte da Caparica, Portugal.
1997–2002: Graduate student, Laboratory of Molecular Genetics, ITQB/UNL, Oeiras, Portugal, and Laboratory of Microbiology, The Rockefeller University, New York, NY, USA.
2002–2007: Post-doc fellow, Laboratory of Molecular Genetics, ITQB/UNL, Oeiras, Portugal.
2003–2007: Invited Assistant Professor, Escola Superior de Biotecnologia, Universidade Católica Portuguesa, Caldas da Rainha, Portugal.
Since 2008: Assistant Researcher, CREM, FCT/UNL, Monte da Caparica, Portugal.

Research Topic

Bacterial stress response In our laboratory we are interested in the detailed characterization of the molecular and cellular stress response mechanisms of bacteria, using as model organism the gram-positive pathogen Staphylococcus aureus and its resistance to β-lactam antibiotics.

Methicillin-resistant Staphylococcus aureus (MRSA) are a leading cause of nosocomial infections worldwide and, in recent years, have also emerged as community acquired pathogens (CA-MRSA), being able to cause lethal infections among otherwise healthy people. Many epidemic MRSA strains are resistant not only to all β-lactams, but also to virtually all classes of antimicrobial agents leaving clinicians with very few therapeutic options.

Although β-lactams, targeting the cell wall synthesis machinery, were the first class of antimicrobial agents to be introduced in the clinical practice, they are still widely used due to their high efficacy, low cost, ease of delivery and minimal side effects. Moreover, in the past 40 years, very few antibiotics representing new chemical classes have reached the clinic.

By understanding in detail how β-lactam resistance is regulated, we might contribute to the design of complementary therapeutic strategies targeting the regulatory mechanisms which eventually will extend the clinical utility of these important class of antimicrobial agents – antibiotic recycling.

In order to achieve this ultimate goal our research efforts are divided in two main themes: follows:
(i) regulatory circuits controlling the expression of β-lactam resistance; (ii) cellular response to β-lactam antibiotics.

Laboratory members

Pedro Arede, PhD student (pedroarede@fct.unl.pt)

Joana Ministro, MSc student (joana_ministro@fct.unl.pt)

Current Funding

• “Role of beta-lactamase operon in the stabilization and expression of methicillin resistance in Staphylococcus aureus”, Fundação para a Ciência e Tecnologia, Lisbon, Portugal. Project: PTDC/BIA-MIC/64071/2006 (2008-2012); PI: Duarte C. Oliveira.

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Recent publications

International Working Group on the Classification of Staphylococcal Cassette Chromosome Elements (IWG-SCC): Ito T, K Hiramatsu, A Tomasz, H de Lencastre, V Perreten, M Holden, D Coleman, R Goering, PM Giffard, RL Skov, K Zhang, H Westh, F O'Brien, FC Tenover, DC Oliveira, S Boyle- Vavra, F Laurent, AM Kearns, B Kreiswirth, KS Ko, H Grundmann, JE Sollid, JF John, R Daum, B Soderquist, G Buist. 2012. “Guidelines for reporting novel mecA gene homologues”. Antimicrob Agents Chemother in press.

Arêde P, C Milheiriço, H de Lencastre and DC Oliveira. 2012. “The anti- repressor MecR2 promotes the proteolysis of the mecA repressor and enables optimal expression of β-lactam resistance in MRSA”. PLoS Pathogens 8: e1002816.

Botelho TO, T. Guevara, A Marrero, P Arêde, VS Fluxà, JL Reymond, DC Oliveira, and FX Gomis-Ruth. 2011. “Structural and functional analyses reveal that Staphylococcus aureus antibiotic resistance factor HmrA is a zinc-dependent endopeptidase”. J Biol Chem, 286: 25697-709.

Oliveira DC and H de Lencastre. 2011. “Methicillin-resistance in Staphylococcus aureus is not affected by the overexpression in trans of the mecA gene repressor: a surprising observation”. PLoS One, 6: e23287.

Milheiriço C, A Portelinha, L Krippahl, H de Lencastre, and DC Oliveira. 2011. “Evidence for a purifying selection acting on the β-lactamase locus in epidemic clones of methicillin-resistant Staphylococcus aureus”. BMC Microbiol, 11: 76-87.

Chen L, JR Mediavilla, DC Oliveira, BM Wiley, H de Lencastre, and BN Kreiswirth. 2009. “Multiplex real-time PCR for rapid staphylococcal cassette chromosome mec (SCCmec)”. J Clin Microbiology 47: 3692-706.

Oliveira DC, M Santos, C Milheiriço, JA Carriço, S Vinga, AL Oliveira, and H de Lencastre. 2008. “ccrB Typing Tool: An online resource for staphylococci ccrB sequence typing.” J Antimicrob Chemother 61: 959-60.

de Lencastre H, DC Oliveira, and A Tomasz. 2007. “Antibiotic resistant Staphylococcus aureus: a paradigm of adaptive power”. Curr Opin Microbiol 10: 428-35.

Oliveira DC, A Tomasz, H de Lencastre. 2002. "Secrets of success of a human pathogen: molecular evolution of pandemic clones of methicillin-resistant Staphylococcus aureus". Lancet Infec Diseas 2: 180-9.

Crisostomo MI, H Westh, A Tomasz, M Chung, DC Oliveira, H de Lencastre. 2001. “The evolution of methicillin resistance in Staphylococcus aureus: similarity of genetic backgrounds in historically early methicillin susceptible and resistant isolates and contemporary epidemic clones”. Proc Nat Acad Sci USA 98: 9865-70.





 

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