Virulence and Immunomodulatory Roles of Bacterial Outer Membrane Vesicles

Abstract

SUMMARY Outer membrane (OM) vesicles are ubiquitously produced by Gram-negative bacteria during all stages of bacterial growth. OM vesicles are naturally secreted by both pathogenic and nonpathogenic bacteria. Strong experimental evidence exists to categorize OM vesicle production as a type of Gram-negative bacterial virulence factor. A growing body of data demonstrates an association of active virulence factors and toxins with vesicles, suggesting that they play a role in pathogenesis. One of the most popular and best-studied pathogenic functions for membrane vesicles is to serve as natural vehicles for the intercellular transport of virulence factors and other materials directly into host cells. The production of OM vesicles has been identified as an independent bacterial stress response pathway that is activated when bacteria encounter environmental stress, such as what might be experienced during the colonization of host tissues. Their detection in infected human tissues reinforces this theory. Various other virulence factors are also associated with OM vesicles, including adhesins and degradative enzymes. As a result, OM vesicles are heavily laden with pathogen-associated molecular patterns (PAMPs), virulence factors, and other OM components that can impact the course of infection by having toxigenic effects or by the activation of the innate immune response. However, infected hosts can also benefit from OM vesicle production by stimulating their ability to mount an effective defense. Vesicles display antigens and can elicit potent inflammatory and immune responses. In sum, OM vesicles are likely to play a significant role in the virulence of Gram-negative bacterial pathogens.

Origin of life: LUCA and extracellular membrane vesicles (EMVs)

“…For many decades the formation of EMVs in prokaryotes was solely focused on bacteria (Kuehn & Kesty 2005;Ellis & Kuehn 2010;Kulp & Kuehn 2010). In bacteria with double membranes (referred to as diderm bacteria) they are generally derived from the outer membrane (OM) which is distinct from the cytoplasmic membrane, and are referred to as OMVs (Kulp & Kuehn 2010).…”

“…OMVs are potent virulence factors of pathogenic diderm bacteria. These vesicles contain toxins, DNA, immunomodulatory compounds, communication factors and adhesins, and have been associated with cytotoxicity, bacterial attachment, intercellular DNA transfer and invasion (Dorward et al 1989;Kuehn & Kesty 2005;Ellis & Kuehn 2010;Maldonado et al 2011;Brown et al 2014). Increased vesiculation has been linked to bacterial stress and may play a role in carrying away toxic compounds, phages or unfolded proteins after exposure to stressful conditions (McBroom & Kuehn 2007;Macdonald & Kuehn 2013).…”

“…Their diverse biological functions have been extensively documented (see Table 1). The list of functions attributed to EMVs includes binding and delivery of nucleic acids, transport of virulence factors, ridding the cell of toxic envelope proteins and tumorigenesis (Deich & Hoyer 1982;Dorward et al 1989;Kadurugamuwa & Beveridge 1997;Kesty et al 2004;Renelli et al 2004;McBroom & Kuehn 2007;Valadi et al 2007;Soler et al 2008;Aldick et al 2009;Ellis & Kuehn 2010;Camussi et al 2011;Rak & Guha 2012;Gaudin et al 2013).…”

Group A streptococci are protected from amoxicillin-mediated killing by vesicles containing -lactamase derived from Haemophilus influenzae

“…Several studies have shown that OMV act as vehicles for protein transfer and interact with the host immune system. [7][8][9] We have previously demonstrated that M. catarrhalis OMV contain β-lactamase, and that secreted OMV protect NTHi and S. pneumoniae from amoxicillin-induced killing. 10 In the present study we investigated whether OMV derived from β-lactam resistant NTHi carry β-lactamase, and if β-lactamasecontaining OMV from NTHi or M. catarrhalis protect GAS from amoxicillin.…”

Bacillus anthracis produces membrane-derived vesicles containing biologically active toxins

“…Secreted vesicles allow bacteria to disperse bacterial products into the surrounding environment in a concentrated manner (10,11). Vesicle formation appears to be a conserved process among both pathogenic and nonpathogenic, Gram-negative bacteria, and the role of outer membrane vesicles in pathogenesis are of great interest.…”