Poster Presentation Melbourne Protein Group Student Symposium 2013

Biophysical analysis of a ‘coupling protein’ involved in Gram-positive bacterial conjugation. (#82)

Von Torres 1 , Daouda Traore 1 , Jessica Wisniewski 2 , Julian Rood 2 , James Whisstock 1
  1. Infection and Immunity Program, Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, Victoria, Australia
  2. Department of Microbiology, Monash University, Clayton, Victoria, Australia

The emergence of antibiotic resistant bacterial infections in Australia is a major health issue due to the limited amount of treatments options available. Antibiotic resistant in bacteria is typically acquired through a horizontal gene transfer process known as ‘conjugation’. Furthermore, this process potentially crosses species barriers and not only disseminates drug resistance genes but also virulence factors. The structural and functional details of bacterial conjugation have been extensively studied in Gram-negative systems, whereas the mediation of this process in the corresponding Gram-positive systems is relatively unknown. The Gram-positive bacterium Clostridium perfringens, contains tetracycline resistant plasmid pCW3 containing a locus encoding for a multiprotein assembly termed the ‘conjugation apparatus’. Through previous studies, key proteins of this locus essential for conjugative transfer of pCW3 have been identified (IntP, TcpA, TcpC to TcpH). This study focuses on the essential conjugation protein TcpA, a putative coupling protein of the pCW3 conjugation apparatus thought to act as either: a receptor for DNA substrates or a possible ATP-dependent translocase. Here we present background and preliminary data on the model Gram-positive coupling protein TcpA, specifically its proposed ATP catalytic and substrate binding properties. Fluorescence and ATP-agarose pull-down assays data are presented assessing for ATP binding. Similarly, gel shift assays were utilised to identify protein-DNA interactions for both sequence specificity and non-specificity. Finally, preliminary crystallization trials of TcpA by itself and in complex with ATP are presented. The determination of the structure and accompanying biophysical, catalytic and binding properties of this essential conjugation protein will assist in establishing the molecular mechanism of conjugative transfer in Gram-positive pathogens.