Poster Presentation The 44th Lorne Conference on Protein Structure and Function 2019

Structural characterisation of the antimicrobial protein BSAP-4 from the gut symbiont Bacteroides vulgatus/dorei species (#217)

Bronte A Johnstone 1 , Craig J Morton 1 , Michelle P Christie 1 , Laurie E Comstock 2 , Michael W Parker 1 3
  1. Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Victoria, Australia
  2. Division of Infectious Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
  3. ACRF Rational Drug Discovery Centre, St Vincent's Institute of Medical Research, Fitzroy, VIC, Australia

The human gut microbiota has been extensively shown to play a critical role in the health of the human host. Furthermore, dysbiosis of the microbiota contributes to numerous diseases. Research is revealing the importance of factors that influence the stability and diversity of the gut microbiome; in particular, the role of interference competition between gut microbial species. Bacteriocins are secreted bacterial peptides/proteins that bind to receptors on target bacterial membranes causing detrimental outcomes, such as cell lysis via pore formation. Recently, a new class of bacteriocins, labelled the Bacteroidales secreted antimicrobialproteins (BSAPs), have been identified. The bacteriocin BSAP-4 secreted fromB. vulgatus/dorei species exhibits potent antimicrobial activity against all strains of B. vulgatus/dorei bacteria, including itself to an extent, the mechanism and advantage of which remains unknown. Furthermore, sequence analysis indicates BSAP-4 lacks homology to any characterised proteins. We aim to characterise BSAP-4 using various structural and biophysical techniques to gain insight into the antimicrobial mechanism for this novel bacteriocin. Progress on the expression, purification, characterisation and crystallisation of BSAP-4 is described here. The antimicrobial properties of bacteriocins may provide a future alternative to conventional antibiotics, which are currently plagued with the global crisis of antibiotic resistance.