Dataset Information

Pathogen-Derived Extracellular Vesicle-Associated Molecules That Affect the Host Immune System: An Overview.

ABSTRACT: Recently, the interest in extracellular vesicles (EVs) released by pathogens like bacteria, fungi, and parasites has rapidly increased. Many of these pathogens actively modulate the immune responses of their host and there is accumulating evidence that pathogen-derived EV contribute to this process. The effects of pathogen-derived EV on the host immune system have been attributed to proteins, lipids, nucleic acids, and glycans contained in, or present on these EV. For example, toxins in bacterial EV can modulate pathogen clearance and antigen presentation, while EV-associated polysaccharides are potential vaccine targets because they induce protective immune responses. Furthermore, parasite EV-associated microRNA may increase parasite survival via host gene repression, and the lipid A moiety of LPS in bacteria-derived EV induces strong pro-inflammatory responses. Research on pathogen EV-associated molecules may pave new avenues to combat infectious diseases by immune intervention. This review provides an overview of the current knowledge of EV-associated molecules released by extracellular pathogens and their effects on the host immune system. The current focus and future hotspots of this rapidly expanding field will be highlighted and discussed.

SUBMITTER: Kuipers ME

PROVIDER: S-EPMC6143655 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Pathogen-Derived Extracellular Vesicle-Associated Molecules That Affect the Host Immune System: An Overview.

Kuipers Marije E ME Hokke Cornelis H CH Smits Hermelijn H HH Nolte-'t Hoen Esther N M ENM

Frontiers in microbiology 20180912

Recently, the interest in extracellular vesicles (EVs) released by pathogens like bacteria, fungi, and parasites has rapidly increased. Many of these pathogens actively modulate the immune responses of their host and there is accumulating evidence that pathogen-derived EV contribute to this process. The effects of pathogen-derived EV on the host immune system have been attributed to proteins, lipids, nucleic acids, and glycans contained in, or present on these EV. For example, toxins in bacteria ...[more]

PMID: 30258429

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Project description:Export of macromolecules via extracellular membrane-derived vesicles (MVs) plays an important role in the biology of Gram-negative bacteria. Gram-positive bacteria have also recently been reported to produce MVs; however, the composition and mechanisms governing vesiculogenesis in Gram-positive bacteria remain undefined. Here, we describe MV production in the Gram-positive human pathogen group A streptococcus (GAS), the etiological agent of necrotizing fasciitis and streptococcal toxic shock syndrome. M1 serotype GAS isolates in culture exhibit MV structures both on the cell wall surface and in the near vicinity of bacterial cells. A comprehensive analysis of MV proteins identified both virulence-associated protein substrates of the general secretory pathway in addition to "anchorless surface proteins." Characteristic differences in the contents, distributions, and fatty acid compositions of specific lipids between MVs and GAS cell membrane were also observed. Furthermore, deep RNA sequencing of vesicular RNAs revealed that GAS MVs contained differentially abundant RNA species relative to bacterial cellular RNA. MV production by GAS strains varied in a manner dependent on an intact two-component system, CovRS, with MV production negatively regulated by the system. Modulation of MV production through CovRS was found to be independent of both GAS cysteine protease SpeB and capsule biosynthesis. Our data provide an explanation for GAS secretion of macromolecules, including RNAs, lipids, and proteins, and illustrate a regulatory mechanism coordinating this secretory response. Group A streptococcus (GAS) is a Gram-positive bacterial pathogen responsible for more than 500,000 deaths annually. Establishment of GAS infection is dependent on a suite of proteins exported via the general secretory pathway. Here, we show that GAS naturally produces extracellular vesicles with a unique lipid composition that are laden with proteins and RNAs. Interestingly, both virulence-associated proteins and RNA species were found to be differentially abundant in vesicles relative to the bacteria. Furthermore, we show that genetic disruption of the virulence-associated two-component regulator CovRS leads to an increase in vesicle production. This study comprehensively describes the protein, RNA, and lipid composition of GAS-secreted MVs and alludes to a regulatory system impacting this process.

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Dataset Information

Pathogen-Derived Extracellular Vesicle-Associated Molecules That Affect the Host Immune System: An Overview.

Publications

Pathogen-Derived Extracellular Vesicle-Associated Molecules That Affect the Host Immune System: An Overview.

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