Assembly and structure of macromolecular complexes involved in bacterial cell wall: biosynthesis and virulence

Abstract

The bacterial cell wall is a complex three-dimensional structure that protects the cell from environmental stress, ensures its shape, and plays key roles in cell division and wall elongation processes. In addition, the cell wall serves as an attachment site for a number of virulence factors and secretion systems, that are necessary not only for infection but often for bacterial survival. In the BACWALL project, we will structurally and functionally characterize key macromolecular complexes involved in cell wall biosysnthesis and repair, such as those formed by Penicillin-Binding Proteins, which play key roles in cell wall formation. In addition, we will also tackle the study of bacterial virulence mechanisms which depend on the cell wall for stability and functionality. We will accomplish these goals through the employment of a combination of X-ray crystallography, biochemistry, molecular biology, and electron microscopy. The applicant will be located both at the LNBio (Campinas) and at the Institut de Biologie Structurale (Grenoble, France), and extensive collaborations will be developed with the electron microscopy group at the LNNano (Campinas). In addition, existing collaboration between the group at the IBS and other European institutes (Institut Pateur, Paris; Univ. Utrecht, The Netherlands; iRTSV, Grenoble) will continue throughout BACWALL, allowing the formation of a network that will include the LNBio and LNNano. The availability of a number of key preliminary results suggests that the work proposed here will succeed in revealing key aspects of peptidoglycan assembly machineries and virulence that will be important not only for the drug development field but also for the understanding of general mechanisms of macromolecular complex formation. (AU)