Poster Presentation Australian Society for Microbiology Annual Scientific Meeting 2016

Burkholderia pseudomallei capsule exacerbates respiratory melioidosis but does not afford protection against antimicrobial signalling or bacterial killing in human olfactory ensheathing cells (#326)

Deepak Samuel Ipe 1 2 , Samantha Dando 2 3 , Michael Batzloff 2 , Matthew Sullivan 4 , David Crossman 5 , Michael Crowley 5 , Emily Strong 2 3 , Stephanie Kyan 2 , Sophie Leclercq 4 6 , Jenny Ekberg 7 8 , James St John 8 , Ifor Beacham 2 , Glen UIett 1 2 9
  1. School of Medical Sciences, Griffith University, Parklands, QLD, Australia
  2. Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia
  3. Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Faculty of Medicine, Nursing and Health Sciences, , Monash University, Clayton, Victoria, Australia
  4. School of Medical Science, and Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia
  5. Genomic Core Lab, Heflin Center for Human Genetics, Birmingham, AL 35294-0024, United States
  6. Research and Development Center, Ezequiel Dias Foundation, Belo Horizonte, Minas Gerais, Brazil
  7. School of Biomedical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia
  8. Eskitis Institute for Drug Discovery, Griffith University, Brisbane, Queensland, Australia
  9. School of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL 35233, United States

Melioidosis, caused by the bacterium Burkholderia pseudomallei, is an often-severe infection that regularly involves respiratory disease following inhalation exposure. Intra-nasal (i.n.) inoculation in mice represents an experimental approach to study the contributions of bacterial capsular polysaccharide I (CPS I) to virulence during acute disease. We used aerosol delivery of B. pseudomallei to establish respiratory infection in mice and studied CPS I in the context of innate immune responses. CPS I improved B. pseudomallei survival in vivo, and triggered multiple cytokine responses, neutrophil infiltration and acute inflammatory histopathology in Spleen, Liver, nasal-associated lymphoid tissue (NALT) and olfactory mucosa (OM). To further explore the role of the OM response to B. pseudomallei infection we infected human olfactory ensheathing cells (OECs) in vitro and measured bacterial invasion and the cytokine responses induced following infection. Human OECs killed >90% of B. pseudomallei in a CPS I independent manner and exhibited an antibacterial cytokine response comprising G-CSF, TNF-alpha and several regulatory cytokines. In-depth genome-wide transcriptomic profiling of the OEC response using RNA sequencing revealed a network of signalling pathways activated in OECs following infection; involving a novel group of 378 genes that encode biological pathways controlling cellular movement, inflammation, immunological disease and molecular transport. This represents the first antimicrobial program to be described in human OECs and establishes the extensive transcriptional defence network accessible within these cells. Collectively, these findings show a role of CPS I in B. pseudomallei survival in vivo following inhalation infection, and the antibacterial signalling network that exists in human OM and OECs.