No Genome is an Island Extra References 9


9. Crossing Cellular, Taxonomic and Weissmann barriers: extracellular transport vesicles (EVs) for protein and nucleic acid transfers between cells.


·      9.A. Diversity and ubiquity of EVs produced by all cells examined; protein, RNA and DNA cargoes. (Deatherage and Cookson 2012; Yanez-Mo, Siljander et al. 2015; Ratajczak and Ratajczak 2016)

o   Marine EVs (Biller, Schubotz et al. 2014; Soler, Krupovic et al. 2015; Biller, McDaniel et al. 2017)


o   Protein cargoes. Proteins in EVs can be of any type. Many are soluble in the enclosed EV lumen, where they are protected from external proteolytic activities. Some cargo proteins may be embedded in the membrane and exposed to the surrounding environment, where they can be recognized by specific receptors on target cells. antigen presentation (Lotvall and Valadi 2007) (Valadi, Ekstrom et al. 2007) (Shenoda and Ajit 2016). In some cases, EVs can use the same cell surface receptors as viruses (van Dongen, Masoumi et al. 2016).


o   DNA cargoes. As mentioned, ocean EVs contain bacterial DNA. Other bacterial and archaeal EVs have been found to contain plasmids and viral genomes as well as chromosomal DNA that can function in intercellular DNA transfer. (Metcalf, Zhang et al. 1997; Gaudin, Krupovic et al. 2014). A hyperthermophilic Archaea was particularly interesting because its EVs collectively contained all of the genome except for a 9.4 kb region, which the authors explained as a consequence of the DNA delivery process.(Choi, Kwon et al. 2015)


o   Plasmid DNA transfer. In addition to observation of EV DNA cargo transfers by fluorescence and PCR analysis, a number of cases of transfers of plasmid DNA via EVs have been directly documented by genetic experiments in prokaryotes:  between E. coli and from E. coli to Salmonella typhimurium (Yaron, Kolling et al. 2000), between Thermococcales kodakaraensis (Archaea) (Gaudin, Gauliard et al. 2013), and between Acinetobacter baylyi as well as from Acinetobacter baylyi to E. coli (Fulsundar, Harms et al. 2014).


·      9.B. Regulated and functional intercellular communication by EV cargo delivery. (Zaborowski, Balaj et al. 2015)

o   Bacterial regulatory proteins and intercellular signals documented to affect EV biogenesis and contents.

§  P. aeruginosa AlgU (Macdonald and Kuehn 2013)

§  Burkholderia quorum-sensing (Kang, Goo et al. 2017)

§  Shigella flexneri virulence plasmid-encoded VirK (Sidik, Kottwitz et al. 2014)

§  Group A Streptococcus CovRS two-component system (Resch, Tsatsaronis et al. 2016)

§  Vibrio fischeri RscS sensor kinase (Shibata and Visick 2012)

§  Serratia marcescens Rcs phosphorelay (McMahon, Castelli et al. 2012).


o   Adaptive EV roles in bacterial populations.

§  Decoys to inhibit bacteriophage infection of Vibrio cholerae (Reyes-Robles, Dillard et al. 2018)

§  E. coli resistance to antimicrobial peptides (AMPs) polymyxin B and colistin (Manning and Kuehn 2011)

§  Biofilm formation by Helicobacter pylori (Grande, Di Marcantonio et al. 2015), Streptoccus mutans (Liao, Klein et al. 2014), Pseudomonas putida (Baumgarten, Sperling et al. 2012), and the oral bacteria Porphyromonas gingivalis and Treponema denticola (Zhu, Dashper et al. 2013)

§  Transmission of the hydrophobic CAI-1 signal molecule between Vibrio harveyi cells (Brameyer, Plener et al. 2018)

§  Delivering degradative enzymes (Schwechheimer, Sullivan et al. 2013)

§  Acquisition of nutrients (Kulp and Kuehn 2010) and minerals such as iron (Lin, Zhang et al. 2017)

§  Predation by Myxococcus xanthus (Evans, Davey et al. 2012)


o   Immune system outcomes (“Yin/Yang effects”) of EV transmission (Zhang, Jiang et al. 2018).  One or both of these functional consequences have been reported for human pathogens Staphylococcus aureus (Song, Sabharwal et al. 2014) (Askarian, Lapek et al. 2018), Yersinia pestis (Eddy, Gielda et al. 2014), and Acinetobacter baumanii (Jin, Kwon et al. 2011), and for the plant pathogen Xylella fastidiosa (Ionescu, Zaini et al. 2014).


o   Animal (largely human) biology subject to EV transmission

§  Paracrine signalling by stem cells (Camussi, Deregibus et al. 2013)

§  Developmental cellular differentiation  (Urbanelli, Magini et al. 2013; Quesenberry, Aliotta et al. 2015)

§  Cardiac physiology (Ibrahim and Marban 2016)

§  Nervous system signalling (Pegtel, Peferoen et al. 2014; Ridder, Keller et al. 2014; Batiz, Castro et al. 2015; Zhang and Yang 2017)

§  Diverse stress responses (Eldh, Ekstrom et al. 2010)

§  Cellular senescence and apoptosis (Urbanelli, Buratta et al. 2016)

§  Immune system activity (Lotvall and Valadi 2007; Valadi, Ekstrom et al. 2007) (Ludwig and Giebel 2012; Shenoda and Ajit 2016)

§  Innate immunity (Buck, Coakley et al. 2014; Benito-Martin, Di Giannatale et al. 2015)

§  Tumor cell proliferation (Cai, Han et al. 2013; Mu, Rana et al. 2013; Ogorevc, Kralj-Iglic et al. 2013; He, Calore et al. 2014; Melo, Sugimoto et al. 2014; Berrondo, Flax et al. 2016; Fonseca, Vardaki et al. 2016; Kawamura, Yamamoto et al. 2017).


o   Uptake of exogenous DNA by sperm (Smith and Spadafora 2005; Spadafora 2007; Zhao, Yu et al. 2012; Arias, Sanchez-Villalba et al. 2017).


o   Reverse Transcriptase required for early embryonic development before being silenced in differentiated cells (Pittoggi, Beraldi et al. 2006; Spadafora 2015)




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