Gram-positive membrane vesicles (MVs): Biogenesis, structure, pathogenicity, and the potential as a delivery platform for antimicrobials

Pneumococcal and group A streptococcal (GAS) infections are major causes of morbidity and mortality globally.

Pneumococci are the major cause of milder respiratory tract infections such as otitis and sinusitis, but also of severe infections such as pneumonia with or without septicemia and meningitis.

GAS are major causes of tonsillitis and skin infections, but also of serious infections including toxic shock syndrome (STSS) and necrotizing fasciitis.

Despite that these gram-positive bacteria are devastating pathogens, they are also common colonizers of the upper respiratory tract from where they may spread to susceptible individuals and cause disease.

Against pneumococcal infections conjugated vaccines have been introduced in the childhood vaccination program with good effect in vaccinated children, but with no success in the adult and elderly due to a vast expansion of non-vaccine types, hampering the vaccine efficacy. Thus, new vaccine approaches are needed.

For GAS, no licensed vaccine exists today. Pneumococcal membrane vesicles (MVs) have by us been shown to be excellent vaccines candidates.

This project aims at identifying the structure and biogenesis pathway, the pathogenicity, and regulatory circuits that control the production of MVs from S. pneumoniae and S. pyogenes. This knowledge is needed to understand the potential of MVs to be used for prevention and as therapy. We also aim at elucidating the potential of using MVs as a delivery platform for antimicrobials.