Sociedade Portuguesa de Microbiologia

Portuguese Society of Microbiology

PhD highlights: Pedro Pereira

Peptidoglycan assembly machines: The Staphylococcus aureus Penicillin-Binding Proteins.

The bacterial cell wall (CW) is of critical importance to cell viability. As there is no equivalent structure to the bacterial CW in mammalian cells, many important antibiotics target enzymes involved in its biosynthesis. The CW structure is mainly composed by two distinct polymers, peptidoglycan (PGN) and wall teichoic acids (WTA).

We are interested in the enzymes that catalyse the final steps of PGN biosynthesis, the penicillin-binding proteins (PBPs), which are targets for a wide range of antibiotics. We used as a model organism the human pathogen S. aureus, an extremely versatile pathogen, which has developed resistance to virtually all classes of available antibiotics, and is currently one of the most common causes of hospital-associated antibiotic resistant-infections.

In this thesis we have shown by fluorescence microscopy that PBPs are recruited to the division septum by different mechanisms, suggesting that each of these enzymes has to arrive at the midcell at a specific stage of the cell cycle. Additionally, we have shown that this recruitment involves not only PGN, synthesized by PBPs, but also WTA a polymer that is crucial in escaping immune-recognition by the host. These findings imply that: 1) for an accurate division, and ultimately for a successful infection, the biosynthesis of the several components of the bacterial surface must be tightly regulated 2) the PBPs seem to play an important role in this regulation by bridging the PGN and WTA biosynthesis pathways.

Acknowledgments: Funding from FCT (SFRH/BD/28443/2006)

PhD course: ITQB PhD program

Year of conclusion: 2013

Institution: Instituto de Tecnologia Química e Biológica

Supervisor: Mariana Gomes de Pinho (mgpinho@itqb.unl.pt)

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