Abstract
The Gram-positive bacterial pathogen, Streptococcus pneumoniae is a major global health threat that kills over one million people worldwide. The pneumococcus commonly colonizes the nasopharynx asymptomatically as a commensal, but is also capable of causing a wide range of life-threatening diseases such as pneumonia, meningitis and septicemia upon migration into the lower respiratory tract and spread to internal organs. Emergence of antibiotic resistant strains and non-vaccine serotypes has led to the classification of pneumococcal bacteria as a priority pathogen by the World Health Organization that needs urgent research into bacterial pathogenesis and development of novel vaccine strategies. Extracellular vesicles are spherical membrane bound structures that are released by both pathogen and host cells, and influence bacterial pathogenesis as well as the immune response. Recent studies have found that while bacterial vesicles shuttle virulence factors and toxins into host cells and regulate inflammatory responses, vesicles released from the infected host cells contain both bacterial and host proteins that are antigenic and immunomodulatory. Bacterial membrane vesicles have great potential to be developed as cell-free vaccine candidates in the future due to their immunogenicity and biostability. Host-derived vesicles isolated from patient biofluids such as blood and bronchoalveolar lavage could be used to identify potential diagnostic biomarkers as well as engineered to deliver desired payloads to specific target cells for immunotherapy. In this review, we summarize the recent developments on the role of bacterial and host vesicles in pneumococcal infections and future prospects in developing novel therapeutics and diagnostics for control of invasive pneumococcal diseases.
Highlights
Streptococcus pneumoniae is a leading cause of mortality and morbidity worldwide due to community-acquired pneumonia and its complications (GBD 2016 Lower Respiratory Infections Collaborators, 2018), out of which the majority are young children below 5 years (McAllister et al, 2019)
Healthy people can be asymptomatically colonized by pneumococci, bacterial invasion into the Extracellular Vesicles in Pneumococcal Infections lower respiratory tract typically causes severe diseases such as pneumonia, septicemia, meningitis and otitis media among the elderly, children and the immunocompromised
We summarize the emerging roles of bacterial- and host- derived vesicles in the pathophysiology of invasive pneumococcal infections
Summary
Streptococcus pneumoniae (the pneumococcus) is a leading cause of mortality and morbidity worldwide due to community-acquired pneumonia and its complications (GBD 2016 Lower Respiratory Infections Collaborators, 2018), out of which the majority are young children below 5 years (McAllister et al, 2019). Bacterial vesicles are 20-250 nm in diameter that are released by both Gram-negative and Gram-positive bacteria and shuttle proteins, carbohydrates, lipids, nucleic acids, and other virulence factors to host cells (Kim et al, 2015). Host EVs released by infected host cells contain pathogen as well as host-derived molecules.
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