title: Halobacterial nano vesicles displaying murine bactericidal permeability-increasing protein rescue mice from lethal endotoxic shock.
abstract: Bactericidal/permeability-increasing protein (BPI) had been shown to possess anti-inflammatory and endotoxin neutralizing activity by interacting with LPS of Gram-negative bacteria. The current study examines the feasibility of using murine BPI (mBPI) expressed on halophilic Archaeal gas vesicle nanoparticles (GVNPs) for the treatment of endotoxemia in high-risk patients, using a murine model of D-galactosamine-induced endotoxic shock. Halobacterium sp. NRC-1was used to express the N-terminal 199 amino acid residues of mBPI fused to the GVNP GvpC protein, and bound to the surface of the haloarchaeal GVNPs. Our results indicate that delivery of mBPIN-GVNPs increase the survival rate of mice challenged with lethal concentrations of lipopolysaccharide (LPS) and D-galactosamine. Additionally, the mBPIN-GVNP-treated mice displayed reduced symptoms of inflammation, including inflammatory anemia, recruitment of neutrophils, liver apoptosis as well as increased pro-inflammatory serum cytokine levels.
authors.affiliation: Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India.
authors.forename: Arjun
authors.initials: A
authors.lastname: Balakrishnan
authors.affiliation: Institute of Marine and Environmental Technology and Department of Microbiology and Immunology, University of Maryland, Baltimore, MD, USA.
authors.forename: Priya
authors.initials: P
authors.lastname: DasSarma
authors.affiliation: Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India.
authors.forename: Oindrilla
authors.initials: O
authors.lastname: Bhattacharjee
authors.affiliation: Institute of Marine and Environmental Technology and Department of Microbiology and Immunology, University of Maryland, Baltimore, MD, USA.
authors.forename: Jong Myoung
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Institute of Marine and Environmental Technology and Department of Microbiology and Immunology, University of Maryland, Baltimore, MD, USA.
authors.forename: Shiladitya
authors.initials: S
authors.lastname: DasSarma
authors.affiliation: Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India.|Center for Biosystem Science and Engineering, Indian Institute of Science, Bangalore, India.
authors.forename: Dipshikha
authors.initials: D
authors.lastname: Chakravortty
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism; D023181:Antimicrobial Cationic Peptides / Q000235:genetics* / Q000378:metabolism; D017209:Apoptosis; D001798:Blood Proteins / Q000235:genetics* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D022162:Cytoplasmic Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D015870:Gene Expression; D006217:Halobacterium / Q000187:drug effects* / Q000502:physiology*; D054884:Host-Pathogen Interactions / Q000235:genetics*; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000009:adverse effects / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D051379:Mice; D011485:Protein Binding; D012772:Shock, Septic / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology* / Q000401:mortality
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; C021623:bactericidal permeability increasing protein