Extracellular vesicles in bacterial and fungal diseases - Pathogenesis to diagnostic biomarkers

Abstract

Intercellular communication among microbes plays an important role in disease exacerbation. Recent advances have described small vesicles, termed as "extracellular vesicles" (EVs), previously disregarded as "cellular dust" to be vital in the intracellular and intercellular communication in host-microbe interactions. These signals have been known to initiate host damage and transfer of a variety of cargo including proteins, lipid particles, DNA, mRNA, and miRNAs. Microbial EVs, referred to generally as "membrane vesicles" (MVs), play a key role in disease exacerbation suggesting their importance in pathogenicity. Host EVs help coordinate antimicrobial responses and prime the immune cells for pathogen attack. Hence EVs with their central role in microbe-host communication, may serve as important diagnostic biomarkers of microbial pathogenesis. In this review, we summarize current research regarding the roles of EVs as markers of microbial pathogenesis with specific focus on their interaction with host immune defence and their potential as diagnostic biomarkers in disease conditions.

Keywords: Biomarkers; extracellular vesicles; infection diagnosis; microbial pathogenesis.

Figure 1.

Schematic diagram illustrating outer inner membrane vesicles (OIMV) of Gram negative bacteria (containing cytoplasmic proteins in addition to the periplasmic space proteins in outer membrane vesicles), cytoplasmic membrane vesicles (CMV) of Gram positive bacteria, fungal extracellular vesicles and exosomes. SOD – superoxide dismutase, PG – peptidoglycan, SabA – sialic acid-binding adhesin, VacA – vacuolating cytotoxin, lnlB – Listeria monocytogenes protein, BlaZ – beta lactamase, Hsp – heat shock protein.

Figure 2.

Host pathogen interactions of M. tuberculosis. Mtb is internalized by the macrophages via host receptors such as C – type lectin and mannose receptors that recognize LAM and LpqH respectively. Once internalized, the pathogen is subjected to intra-phagosomal processing. Mtb survives by producing molecules such as ptpA (that prevents phagosome acidification) and inhibition of secretion of coronin (important for lysosome – phagosome fusion). Mtb also induces T cell anergy and hampers the production of IFNγ by T cells and natural killer cells rendering them unable to activate the macrophage. LpqH released from lysis of Mtb are utilized by host to induce maturation of dendritic cells which then travel to lymph nodes to prime B cells for clearing of Mtb. Mtb is able to survive iron starvation by enhancing secretion of vesicles charged with mycobactin (siderophore). These key molecules can potentially serve as efficacious diagnostic biomarkers of TB.