Complexities of cell-to-cell communication through membrane vesicles: implications for selective interaction of membrane vesicles with microbial cells.

Abstract

Interaction between microbes in multicellular communities contributes to the development of complex microbial ecosystems. The secretion of various substances such as extracellular toxic compounds for combatting predation, extracellular DNA for horizontal gene transfer (HGT) and quorum-sensing (QS) signals for cell density-dependent cooperation, greatly influences microbial interactions (Hibbing et al., 2010; Tashiro et al., 2013). Study of the diffusion of substances secreted from donor cells to the extracellular environment and their uptake by recipient cells offers valuable insights for understanding microbial interactions. The existence of membrane vesicles (MVs) increases the complexity involved in the diffusion of secreted substances during microbial interactions. MVs are extracellular particle-like liposome structures ranging from 20 to 200 nm in diameter (Figure ​(Figure1A)1A) and are pinched off from the external membrane of the microbe. The phenomenon of MV secretion has been observed in Gram-negative bacteria; however, recent studies have indicated that MVs are also produced by other prokaryotes including Gram-positive bacteria and archaea (Beveridge, 1999; Tashiro et al., 2010a, 2012; Haurat et al., 2015). MVs encapsulate membranal, periplasmic, and cytoplasmic components and play a role in the transfer of several compounds to organisms including both prokaryotic and eukaryotic cells. MVs contain proteins, DNA, RNA and in some cases, quorum sensing signals, and these substances are transferred to cells. Compared with freely-diffused chemical compounds secreted from bacteria, MVs have the following unique characteristics: (1) several chemical substances are highly concentrated in MVs, (2) interior substances in MVs are protected against environmental stresses, and (3) MVs play a role in effectively delivering these substances to cells. In this opinion article, we highlight the characteristics of MVs stated above and discuss the possibility of MV-mediated selective delivery to target cells (Figure ​(Figure1B1B). Figure 1 (A) The conceptual structure of membrane vesicles (MVs) derived from Gram-negative bacteria. MVs are composed of phospholipids, membrane proteins and lipopolysaccharides. In addition, various kinds of substances including DNA, exoproteins and quorum-sensing ... Highly concentrated substances in MVs The significant characteristic of MVs is their ability to encapsulate specific substances. Interior substances are maintained at high concentration and are protected from degradation by exterior stresses and enzymes. In the case of Pseudomonas aeruginosa, which is not only known as an opportunistic pathogen but also known to inhabit a variety of environments, a total of 68% of phospholipase C and 50% of alkaline phosphatase in the supernatant are localized in MVs along with the highly concentrated murein hydrolase (Kadurugamuwa and Beveridge, 1995, 1996). The encapsulation of toxic proteins provides an effective means for toxic transfer to not only eukaryotic cells but also other bacteria to counteract predation in the environment (Li et al., 1998; Evans et al., 2012). Furthermore, 86% of the Pseudomonas quinolone signal, which is one of the QS signals of P. aeruginosa, is localized in MVs, although smaller percentages (<1%) of other QS signals, including acyl-homoserine lactones, are localized in MVs (Mashburn and Whiteley, 2005). Such a highly concentrated QS signal is likely to effectively facilitate rapid alteration of gene expression in recipient cells. DNA is also highly concentrated in MVs, and MV-associated DNA is protected against extracellular DNase (Renelli et al., 2004). Several studies indicated that encapsulation of DNA contributes to HGT (Kolling and Matthews, 1999; Yaron et al., 2000; Fulsundar et al., 2014). Thus, the encapsulation of various signals in MVs plays an important role in microbial communications including QS and HGT, and increases effectiveness compared with diffusion-based interactions.