Dataset Information

Immunoediting role for major vault protein in apoptotic signaling induced by bacterial N-acyl homoserine lactones.

ABSTRACT: The major vault protein (MVP) mediates diverse cellular responses, including cancer cell resistance to chemotherapy and protection against inflammatory responses to Pseudomonas aeruginosa Here, we report the use of photoactive probes to identify MVP as a target of the N-(3-oxo-dodecanoyl) homoserine lactone (C12), a quorum sensing signal of certain proteobacteria including P. aeruginosa. A treatment of normal and cancer cells with C12 or other N-acyl homoserine lactones (AHLs) results in rapid translocation of MVP into lipid raft (LR) membrane fractions. Like AHLs, inflammatory stimuli also induce LR-localization of MVP, but the C12 stimulation reprograms (functionalizes) bioactivity of the plasma membrane by recruiting death receptors, their apoptotic adaptors, and caspase-8 into LR. These functionalized membranes control AHL-induced signaling processes, in that MVP adjusts the protein kinase p38 pathway to attenuate programmed cell death. Since MVP is the structural core of large particles termed vaults, our findings suggest a mechanism in which MVP vaults act as sentinels that fine-tune inflammation-activated processes such as apoptotic signaling mediated by immunosurveillance cytokines including tumor necrosis factor-related apoptosis inducing ligand (TRAIL).

SUBMITTER: Rayo J

PROVIDER: S-EPMC8000436 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Immunoediting role for major vault protein in apoptotic signaling induced by bacterial N-acyl homoserine lactones.

Rayo Josep J Gregor Rachel R Jacob Nicholas T NT Dandela Rambabu R Dubinsky Luba L Yashkin Alex A Aranovich Alexander A Thangaraj Manikandan M Ernst Orna O Barash Eran E Malitsky Sergey S Florea Bogdan I BI Krom Bastiaan P BP Wiemer Erik A C EAC Kickhoefer Valerie A VA Rome Leonard H LH Mathison John C JC Kaufmann Gunnar F GF Overkleeft Herman S HS Cravatt Benjamin F BF Zor Tsaffrir T Janda Kim D KD Ulevitch Richard J RJ Kravchenko Vladimir V VV Meijler Michael M MM

Proceedings of the National Academy of Sciences of the United States of America 20210301 12

The major vault protein (MVP) mediates diverse cellular responses, including cancer cell resistance to chemotherapy and protection against inflammatory responses to Pseudomonas aeruginosa Here, we report the use of photoactive probes to identify MVP as a target of the N-(3-oxo-dodecanoyl) homoserine lactone (C12), a quorum sensing signal of certain proteobacteria including P. aeruginosa. A treatment of normal and cancer cells with C12 or other N-acyl homoserine lacton ...[more]

PMID: 33723037

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Project description:Bacteria need to be isolated in pure culture to gain access to the wide array of interesting functions they conceal. This is challenging because they do not live in isolation but instead in communities where they actively communicate and interact with each other. In this study, we aimed to increase the culturability of soil bacteria using three different signaling molecules: N-(3-oxohexanoyl)-L-homoserine lactone, N-octanoyl-L-homoserine lactone, and 3',5'-cyclic adenosine monophosphate (cAMP). The signals were added individually to soils suspended in PBS buffer to a final concentration of 5 µM. Soil suspensions were agitated for 24 hours, after which they were serially diluted and plated on tenfold-diluted Reasoner's 2A agar that either contained or did not contain the same signaling molecule used during the extraction step. DNA was isolated from both soil suspensions and grown cultures and, after a high-throughput amplicon sequencing, differences in bacterial abundances and diversity were determined across treatments. To further explain the action of the signaling molecules on the treated soil communities, their metagenomic functions were predicted using the software PICRUSt2. N-octanoyl-L-homoserine lactone was found to increase the diversity observed on solid media, while N-(3-oxohexanoyl)-L-homoserine lactone and cAMP were not. Potentially novel isolates aided by the signaling molecules were affiliated with the genera Pseudomonas and Nocardioides. IMPORTANCE Microorganisms are a repository of interesting metabolites and functions. Therefore, accessing them is an important exercise for advancing not only basic questions about their physiology but also to advance technological applications. In this sense, increasing the culturability of environmental microorganisms remains an important endeavor for modern microbiology. Because microorganisms do not live in isolation in their environments, molecules can be added to the cultivation strategies to "inform them" that they are present in growth-permissive environmental conditions. Signaling molecules such as acyl-homoserine lactones and 3',5'-cyclic adenosine monophosphate belong to the plethora of molecules used by bacteria to communicate with each other in a phenomenon called quorum sensing. Therefore, including quorum sensing molecules can be an incentive for microorganisms, specifically soil bacteria, to increase their numbers on solid media.

Dataset Information

Immunoediting role for major vault protein in apoptotic signaling induced by bacterial N-acyl homoserine lactones.

Publications

Immunoediting role for major vault protein in apoptotic signaling induced by bacterial <i>N</i>-acyl homoserine lactones.

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