Bacterial Membrane Vesicles in Pneumonia: From Mediators of Virulence to Innovative Vaccine Candidates.

Felix Behrens,Teresa C Funk-Hilsdorf,Szandor Simmons,Wolfgang M Kuebler

doi:10.3390/ijms22083858

Abstract

Pneumonia due to respiratory infection with most prominently bacteria, but also viruses, fungi, or parasites is the leading cause of death worldwide among all infectious disease in both adults and infants. The introduction of modern antibiotic treatment regimens and vaccine strategies has helped to lower the burden of bacterial pneumonia, yet due to the unavailability or refusal of vaccines and antimicrobials in parts of the global population, the rise of multidrug resistant pathogens, and high fatality rates even in patients treated with appropriate antibiotics pneumonia remains a global threat. As such, a better understanding of pathogen virulence on the one, and the development of innovative vaccine strategies on the other hand are once again in dire need in the perennial fight of men against microbes. Recent data show that the secretome of bacteria consists not only of soluble mediators of virulence but also to a significant proportion of extracellular vesicles—lipid bilayer-delimited particles that form integral mediators of intercellular communication. Extracellular vesicles are released from cells of all kinds of organisms, including both Gram-negative and Gram-positive bacteria in which case they are commonly termed outer membrane vesicles (OMVs) and membrane vesicles (MVs), respectively. (O)MVs can trigger inflammatory responses to specific pathogens including S. pneumonia, P. aeruginosa, and L. pneumophila and as such, mediate bacterial virulence in pneumonia by challenging the host respiratory epithelium and cellular and humoral immunity. In parallel, however, (O)MVs have recently emerged as auspicious vaccine candidates due to their natural antigenicity and favorable biochemical properties. First studies highlight the efficacy of such vaccines in animal models exposed to (O)MVs from B. pertussis, S. pneumoniae, A. baumannii, and K. pneumoniae. An advanced and balanced recognition of both the detrimental effects of (O)MVs and their immunogenic potential could pave the way to novel treatment strategies in pneumonia and effective preventive approaches.

Highlights

Pneumonia as the most common lower respiratory tract infection is the leading cause of infection-associated death worldwide, and the fourth most common cause of death globally [1,2]
In this review we summarize recent insights into the emerging role of bacterial membrane vesicles in the pathophysiology of
The (O)membrane vesicles (MVs)–epithelial interaction is not limited to membrane binding, since P. aeruginosa outer membrane vesicles (OMVs) are able to fuse with bronchial epithelial cells [75], and (O)MVs from several bacteria such as A. baumannii and S. pneumoniae can be incorporated by alveolar epithelial cells [51,70,76]

Summary

Introduction

Pneumonia as the most common lower respiratory tract infection is the leading cause of infection-associated death worldwide, and the fourth most common cause of death globally [1,2]. Extracellular membrane vesicles released from bacteria are increasingly recognized as molecular shuttles of nucleic acids, proteins, lipids, and carbohydrates involved in bacterial pathogenicity with the ability to target and (de)regulate host cells. The species of pathogens causing bacterial pneumonia are manifold, almost all strains release OMVs or MVs, respectively.

Results

Conclusion