Poster Presentation BACPATH 2022

Defining the 'Glycointeractome' of the multi-drug resistant pathogen Acinetobacter baumannii. (#127)

Nuala Ellaby 1 , Greg Tram 1 , Jessica Poole 1 , Felise G Adams 2 , Michael P Jennings 1 , Glen Ulett 3 , Bart A Eijkelkamp 2 , John M Atack 1 4
  1. Institute for Glycomics, Gold Coast , QLD, Australia
  2. Molecular Science and Technology, College of Science and Engineering, Flinders University, Adelaide, SA, Australia
  3. School of Pharmacy and Medical Science and Menzies Health Institute , Griffith University , Gold Coast , QLD, Australia
  4. School of Environment and Science, Griffith University, Gold Coast , QLD, Australia

Acinetobacter baumannii is a major multi-drug resistant nosocomial pathogen and the cause of a significant number of hospital-acquired infections worldwide. A. baumannii is rapidly becoming resistant to all currently used antibiotics, and as such it is considered a critical top priority pathogen by the World Health Organisation and the Centers for Disease Control and Prevention. A. baumannii encodes several major outer membrane proteins that have all previously been determined to be involved in host adherence, and more broadly in pathobiology, but the specific host receptors that these outer-membrane proteins interact with remains undefined. We have demonstrated, for the first time, that a major A. baumannii surface adhesin, Ata, interacts with host glycans with high-affinity, specifically glycan structures containing galactose and N-acetylglucosamine. The interaction of Ata with the host extracellular matrix (ECM) protein fibronectin, which is heavily glycosylated, was absolutely dependent of the presence of these glycan structures, as no interaction between Ata and deglycosylated fibronectin occurred. Further, we demonstrate that two other major outer-membrane proteins from A. baumannii, OmpA, a major porin, and FhaB, filamentous haemagglutinin, also interact with host glycans. Our biophysical data, generated using a parallel approach of heterologous over-expression of each adhesin at the E.coli cell surface, characterisation of purified protein, and study of knock-out mutants in A. baumannii demonstrates that major A. baumannii virulence factors all have a requirement for glycan structures in order to interact with host cells and proteins. This knowledge will enable further investigation of precisely how A. baumannii interacts with the human host, and pave the way for new ways to treat infections caused by a major human pathogen for which traditional antibiotics are rapidly becoming ineffective.