Structural biochemistry of enzymes involved in biosynthesis of c-di-AMP in Staphylococcus aureus

• Grant number: 12/01321-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: April 01, 2012
• End date: March 31, 2016
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Marcos Vicente de Albuquerque Salles Navarro
• Grantee: Nathalya Cristina de Moraes Roso Mesquita
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil

Abstract

Staphylococcus aureus is an important human pathogen that colonizes mainly the nostrils and skin, leading to a series of invasive infections. Recently, the number of infections caused by strains resistant to several super antibiotics indicates the need to search for new treatments. Accordingly, new targets for drug development have been explored and bacterial cell wall, which structures are essential for infection, appears as a grat opportunity for research. It has been shown that one of these structures, the lipoteichoic acid (LTA), is essential for the growth of super-resistant strains of S. aureus, but even mutants unable to synthesize LTA recovered almost normal growth after an additional mutation in the phosphodiesterase Sa_GdpP. Together with the di-adenylate cyclase Sa_DacA, Sa_GdpP is responsible for the maintenance of intracellular levels of the new bacterial signaling molecule c-di-AMP. In S. aureus, increased levels of this molecule enhances the ability of bacteria to deal with cell wall stress. Seeking a better of c-di-AMP turnover in S. aureus, this project aims at solving the three-dimensional structures of Sa_GdpP Sa_DacA through X-ray crystallography. Coupled to this technique, we will employ biophysical and biochemical characterization in order to propose mechanisms of activity for these two enzymes. The results generated in this project may provide a basis for the development of new therapies against the infection of super-resistant strains of S. aureus.

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

MESQUITA, Nathalya Cristina de Moraes Roso. Structural and functional studies of the unique diadenylate cyclase enzyme and the unique YbbR-like protein in Staphylococcus aureus: proteins involved in c-di-AMP biosynthesis. 2016. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Física de São Carlos (IFSC/BT) São Carlos.