Study of structural proteins of the bacterial DNA

• Grant number: 20/09328-2
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: October 01, 2021
• End date: September 30, 2026
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Rogério Ferreira Lourenço
• Grantee: Rogério Ferreira Lourenço
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Cristina Elisa Alvarez Martinez ; Marcelo Brocchi ; Marina Rovani Drummond ; Paulo Eduardo Neves Ferreira Velho
• Associated research grant(s): 23/01591-4 - Determination of the distribution pattern of the GapR protein along the nucleoid of Bartonella henselae, AP.R
• Associated scholarship(s): 24/14378-0 - Uncovering the molecular mechanisms involved in the regulation of H-NS proteins in the bacterium Burkholderia cenocepacia, BP.MS; 22/11503-2 - An interactome analysis of a Burkholderia cenocepacia nucleoid-associated protein, BP.IC; 22/09916-7 - Analysis of the interaction of histone-H-NS motif-containing proteins with the bacterial genetic material, BP.MS; 22/11051-4 - Study of the functional and structural diversity of a nucleoid-associated protein family, BP.DD; 21/12236-5 - Study of structural proteins of the bacterial DNA, BP.JP

Abstract

Bacteria organize their genetic material in a compact and dynamic structure, the nucleoid. This complex organization of the genetic material is achieved in part by the action of a series of proteins referred to as nucleoid-associated proteins (NAPs). Upon binding, NAPs alter local DNA structure. As the changes in DNA structure driven by NAPs are distinct from those induced by histones in eukaryotic cells, NAPs represent a potential target to control the bacterial growth and offer an alternative to the use of antibiotic. Owing to their effect on DNA structure, NAPs also modulate global gene expression. The role of NAPs in the organization of DNA and gene expression regulation has been investigated in a few bacterial species. In Escherichia coli and Salmonella enterica, the NAP H-NS compacts DNA and silences gene expression by bridging adjacent segments of the chromosome. A comparison of the deduced amino acid sequences of H-NS orthologs suggests that these proteins may differ from each other with respect to the oligomerization and DNA binding properties. Nonetheless, the extent to which these structural differences among the H-NS orthologs impacts the way the H-NS orthologs organize DNA and affect gene expression in different bacteria is not clear. This research proposal aims to analyze the structural and functional similarities among H-NS proteins by characterizing a short form of H-NS in the bacterium Bartonella henselae. Additionally, we aim to expand the repertory of potential targets for the bacterial control by studying new NAPs in Burkholderia cenocepacia. Also, a study aiming the identification of synthetic peptides with inhibitory function toward a B. cenocepacia NAP is proposed here. (AU)