title: Lactobacillus-derived extracellular vesicles enhance host immune responses against vancomycin-resistant enterococci.
abstract: Probiotic bacteria are known to modulate host immune responses against various pathogens. Recently, extracellular vesicles (EVs) have emerged as potentially important mediators of host-pathogen interactions. In this study, we explored the role of L. plantarum derived EVs in modulating host responses to vancomycin-resistant Enterococcus faecium (VRE) using both Caenorhabditis elegans and human cells.
  
  
  
  Our previous work has shown that probiotic conditioning C. elegans with L. acidophilus NCFM prolongs the survival of nematodes exposed to VRE. Similarly, L. plantarum WCFS1 derived extracellular vesicles (LDEVs) also significantly protected the worms against VRE infection. To dissect the molecular mechanisms of this EV-induced protection, we found that treatment of C. elegans with LDEVs significantly increased the transcription of host defense genes, cpr-1 and clec-60. Both cpr-1 and clec-60 have been previously reported to have protective roles against bacterial infections. Incubating human colon-derived Caco-2 cells with fluorescent dye-labeled LDEVs confirmed that LDEVs could be transported into the mammalian cells. Furthermore, LDEV uptake was associated with significant upregulation of CTSB, a human homologous gene of cpr-1, and REG3G, a human gene that has similar functions to clec-60.
  
  
  
  We have found that EVs produced from L. plantarum WCFS1 up-regulate the expression of host defense genes and provide protective effects on hosts. Using probiotic-derived EVs instead of probiotic bacteria themselves, this study provides a new direction to treat antimicrobial resistant pathogens, such as VRE.
authors.affiliation: Division of Infectious Diseases, The Warren Alpert Medical School of Brown University, Providence, RI, 02903, USA. ming.li@brown.edu.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Division of Infectious Diseases, The Warren Alpert Medical School of Brown University, Providence, RI, 02903, USA.
authors.forename: Kiho
authors.initials: K
authors.lastname: Lee
authors.affiliation: Division of Infectious Diseases, The Warren Alpert Medical School of Brown University, Providence, RI, 02903, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Hsu
authors.affiliation: Division of Infectious Diseases, The Warren Alpert Medical School of Brown University, Providence, RI, 02903, USA.
authors.forename: Gerard
authors.initials: G
authors.lastname: Nau
authors.affiliation: Division of Infectious Diseases, The Warren Alpert Medical School of Brown University, Providence, RI, 02903, USA.
authors.forename: Eleftherios
authors.initials: E
authors.lastname: Mylonakis
authors.affiliation: Division of Infectious Diseases, The Warren Alpert Medical School of Brown University, Providence, RI, 02903, USA.|COBRE Center for Cancer Research, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI, 02903, USA.|Clinical Research Center of Lifespan, Providence, RI, 02903, USA.
authors.forename: Bharat
authors.initials: B
authors.lastname: Ramratnam
mesh_terms: D000818:Animals; D018938:Caco-2 Cells / Q000276:immunology / Q000382:microbiology; D017173:Caenorhabditis elegans / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D002470:Cell Survival; D000067128:Extracellular Vesicles / Q000276:immunology* / Q000378:metabolism* / Q000648:ultrastructure; D005786:Gene Expression Regulation; D016908:Gram-Positive Bacterial Infections / Q000382:microbiology; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D007778:Lactobacillus / Q000378:metabolism*; D048191:Lactiplantibacillus plantarum / Q000378:metabolism; D008854:Microscopy, Electron; D019936:Probiotics / Q000627:therapeutic use*; D065507:Vancomycin-Resistant Enterococci / Q000276:immunology* / Q000472:pathogenicity*
keywords: CTSB; Extracellular vesicles; LDEVs; Lactobacillus; REG3G; VRE; Vancomycin-resistant enterococci