dco

Duarte C. Oliveira
Assistant Researcher
Integrated Member
Research Group
Molecular Microbiology
Research Interests
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 beta-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.
Main publications
1. Arêde P, T Botelho, T Guevara, I Usón, DC Oliveira and FX Gomis-Rüth. 2013. “Structure-function studies of the staphylococcal methicillin resistance anti-repressor, MecR2”. J Biochem Chem 288: 21267-78.

2. Arêde P, J Ministro, and DC Oliveira. 2013. “Redefining the role of the β-lactamase Locus in methicillin-resistant Staphylococcus aureus: β-Lactamase regulators disrupt the MecI-mediated strong repression on mecA and optimize the phenotypic expression of resistance in strains with constitutive mecA expression”. Antimicrob Agents Chemother 57: 3037-45.

3. Arêde P, and DC Oliveira. 2013. “Proteolysis of mecA repressor is essential for expression of methicillin resistance by Staphylococcus aureus”. Antimicrob Agents Chemother 57:2001-2

4. 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.

5. 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.