SCAN: Studies on methicillin-resistance chromosomal cassette in Staphylococcus aureus

SCAN Seminar

Title: Studies on methicillin-resistance chromosomal cassette in Staphylococcus aureus: new typing strategies and insights into the regulation of resistance

Speaker: Catarina Milheiriço

Laboratory: Molecular Genetics Laboratory

Abstract

Staphylococcus aureus is among the most important human pathogens causing both hospital and community-acquired infections worldwide. Methicillin resistant S. aureus (MRSA) not only developed resistance to virtually all beta-lactams, but has also accumulated resistance traits to other unrelated classes of antimicrobial agents. The central element of methicillin resistance, the mecA gene, is embedded in a large heterologous mobile genetic element, so called Staphylococcal Cassette Chromosome mec (SCCmec).

Several SCCmec types and subtypes have been identified in S. aureus. The molecular characterization of a large number of MRSA clinical isolates recovered worldwide has shown that MRSA have a strong clonal structure, and just a few highly epidemic clones, characterized by specific genetic backgrounds and SCCmec types, are responsible for the majority of infections worldwide. Under this perspective, SCCmec typing strategies have been established as essential tools for the proper characterization and identification of MRSA clones, as well as to elucidate the origin(s) and evolutionary history of contemporary MRSA clones.
In order to decrease the burden of MRSA infections, it is of critical importance to better understand the mechanism(s) involved in the expression of methicillin resistance.

The mecA transcription may be co-regulated by two regulatory systems composed of a repressor and a sensor/inducer: the mecI-mecR1 system (where mecI gene encodes for a transcription repressor, while mecR1 gene encodes for a beta-lactam transmembrane sensory transducer) and the homologous blaI-blaR1 system of the beta-lactamase regulon coding for resistance to penicillins. The full characterization of the molecular mechanisms involved in the induction of the mecA transcription remains to be clarified; namely, the precise role of beta-lactamase genes in contemporary MRSA strains and the signal transduction mechanism between the activated inducer and the repressor. Our results provide evidence for the existence of a novel regulatory gene, mecR2, involved in the mecA transcriptional control, suggesting that the current model for the mecA regulation needs revision.

Short CV:
2004 – Degree in “Biologia Microbiana e Genética” by Faculdade de Ciências de Lisboa, Universidade de Lisboa.
November 2004 – December 2005: Research student in the Laboratory of Molecular Genetics at ITQB, under the supervision of Professor Hermínia de Lencastre and Dr. Duarte Oliveira.
Since January 2006 – PhD student in the Laboratory of Molecular Genetics at ITQB, under the supervision of Professor Hermínia de Lencastre and Dr. Duarte Oliveira. Research area: Studies on methicillin-resistance chromosomal cassette in Staphylococcus aureus and mechanism(s) involved in the expression of methicillin resistance.