Abstract
Byrne, James
PhD candidate, Bacterial Pathogenesis Research Institute, Paton Lab, Discipline of Microbiology and Immunology, School of Molecular and Biomedical Sciences,
The University of Adelaide
'Disrobing a pathogen': the role of the protein, CpsC, in the production of the pneumococcal overcoat
Streptococcus pneumoniae, commonly known as the pneumococcus, is the leading cause of pneumonia and meningitis worldwide and is responsible for the death of a million children under the age of 5 annually. The capsular polysaccharide (CPS) produced by the pneumococcus is key to the bacterium's ability to cause these serious invasive diseases. With the CPS layer forming the outermost structure on the bacterium's surface the pneumococcus can hide itself from the immune system, and in doing so, infiltrate the lungs, blood and brain of the host.
The production of CPS is tightly controlled through two distinct mechanisms. One of these mechanisms relies on the interactions between three proteins, CpsB, CpsC and CpsD which exert a level of control by acting as a 'molecular switch' that can be 'flipped' to either production or attachment of CPS to the outside of the bacterium.
My work has shown that when a component of the 'switch', specifically CpsC, is broken we are left with a bacterial cell incapable of alternating between production and attachment of CPS, resulting in an overall drop in the quantity of CPS on the surface of the bacterial cell. Without its overcoat (the CPS layer) the bacterium is 'disrobed' and exposed to the immune system which can now easily detect and remove even the most virulent strains. Importantly, a section of CpsC is exposed to the outside of the cell making it a good potential target for drug design in an era of waning vaccine efficacy and widespread antibiotic resistance.