Poster Presentation Lorne Infection and Immunity 2019

A longitudinal study on the effect of plasmapheresis on the Pseudomonas aeruginosa population in the lung (#178)

Emma Sheehan 1 , Adam F Cunningham 2 , Timothy J Wells 3 , Ian R Henderson 1
  1. Institute of Microbiology and Infection, The University of Birmingham, Birmingham, United KIngdom
  2. Institute of Immunology and Immunotherapy, The University of Birmingham, Birmingham, United Kingdom
  3. Diamantina Institute, The University of Queensland, Brisbane, Queensland, Australia

Pseudomonas aeruginosa is a Gram negative, opportunistic human pathogen, which is beginning to pose a major challenge in healthcare settings. P. aeruginosa is frequently found to be a causative agent of pneumonia and urinary tract infections in hospitalised patients and commonly infects immunocompromised individuals, including those suffering from burn wounds, cystic fibrosis (CF) and bronchiectasis.

Chronic colonisation with this bacterium has been associated with more severe disease in patients suffering from non-CF bronchiectasis. It has recently been shown that ~20% of these patients overproduce IgG2 antibodies (inhibitory antibodies) specific to their colonising strain. Production of these antibodies has been shown to protect the bacteria from serum-mediated killing and correlates with an increase in morbidity and mortality.

We recently reported the use plasmapheresis as a potential novel treatment option for patients with bronchiectasis, chronic P. aeruginosa infection and inhibitory antibodies. Analysis of the serum resistance profiles and LPS specific antibody binding patterns of longitudinal isolates obtained from these patients identified differences between isolates which may provide further insight into the mechanism of inhibitory antibodies.

Here we genome sequenced all longitudinal isolates taken from the patients post plasmapheresis. SNP analysis was used to identify possible mechanisms for the changes in serum-resistance phenotype. Mutants in these identified genes have been created to confirm their role in the phenotype switch. Understanding the mechanism by which inhibitory antibodies protect the bacteria from serum mediated killing has the potential to identify novel therapeutic targets and is fundamental for the improvement of current diagnostic and treatment options.

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  2. Wells, T.J., Whitters, D., Sevastsyanovich, Y.R., Heath, J.N., Pravin, J., Goodall, M., Browning, D.F., O'Shea, M.K., Cranston, A., De Soyza, A., Cunningham, A.F., MacLennan, C.A., Henderson, I.R. & Stockley, R.A., (2014) Increased severity of respiratory infections associated with elevated anti-LPS IgG2 which inhibits serum bactericidal killing. J Exp Med 211: 1893-1904.
  3. Wells, T.J., Davison, J., Sheehan, E., Kanagasundaram, S., Spickett, G., MacLennan, C.A., Stockley, R.A., Cunningham, A.F., Henderson, I.R. & De Soyza, A., (2017) The Use of Plasmapheresis in Patients with Bronchiectasis with Pseudomonas aeruginosa Infection and Inhibitory Antibodies. Am J Respir Crit Care Med 195: 955-958.