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

2021 ◽  
Vol 118 (12) ◽  
pp. e2012529118
Author(s):  
Josep Rayo ◽  
Rachel Gregor ◽  
Nicholas T. Jacob ◽  
Rambabu Dandela ◽  
Luba Dubinsky ◽  
...  

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).

2000 ◽  
Vol 182 (24) ◽  
pp. 6921-6926 ◽  
Author(s):  
Jared R. Leadbetter ◽  
E. P. Greenberg

ABSTRACT Acyl-homoserine lactones (acyl-HSLs) serve as dedicated cell-to-cell signaling molecules in many species of the classProteobacteria. We have addressed the question of whether these compounds can be degraded biologically. A motile, rod-shaped bacterium was isolated from soil based upon its ability to utilizeN-(3-oxohexanoyl)-l-homoserine lactone as the sole source of energy and nitrogen. The bacterium was classified as a strain of Variovorax paradoxus. TheV. paradoxus isolate was capable of growth on all of the acyl-HSLs tested. The molar growth yields correlated with the length of the acyl group. HSL, a product of acyl-HSL metabolism, was used as a nitrogen source, but not as an energy source. Cleavage and partial mineralization of the HSL ring were demonstrated by using radiolabeled substrate. This study indicates that some strains of V. paradoxus degrade and grow on acyl-HSL signals as the sole energy and nitrogen sources. This study provides clues about the metabolic pathway of acyl-HSL degradation by V. paradoxus.


2004 ◽  
Vol 70 (7) ◽  
pp. 4387-4389 ◽  
Author(s):  
Michael W. Taylor ◽  
Peter J. Schupp ◽  
Harriet J. Baillie ◽  
Timothy S. Charlton ◽  
Rocky de Nys ◽  
...  

ABSTRACT We report for the first time the production of acyl homoserine lactones (AHLs) by bacteria associated with marine sponges. Given the involvement of AHLs in bacterial colonization of many higher organisms, we speculate that such quorum sensing signals could play a part in interactions between sponges and the dense bacterial communities living within them.


2008 ◽  
Vol 75 (1) ◽  
pp. 45-53 ◽  
Author(s):  
Ryan W. Shepherd ◽  
Steven E. Lindow

ABSTRACT Plant aerial surfaces comprise a complex habitat for microorganisms, and many plant-associated bacteria, such as the pathogen Pseudomonas syringae, exhibit density-dependent survival on leaves by utilizing quorum sensing (QS). QS is often mediated by diffusible signals called N-acyl-homoserine lactones (AHLs), and P. syringae utilizes N-3-oxo-hexanoyl-dl-homoserine lactone (3OC6HSL) to control traits influencing epiphytic fitness and virulence. The P. syringae pathovar syringae B728a genome sequence revealed two putative AHL acylases, termed HacA (Psyr_1971) and HacB (Psyr_4858), which are N-terminal nucleophile hydrolases that inactivate AHLs by cleaving their amide bonds. HacA is a secreted AHL acylase that degrades only long-chain (C ≥ 8) AHLs, while HacB is not secreted and degrades all tested AHLs. Targeted disruptions of hacA, hacB, and hacA and hacB together do not alter endogenous 3OC6HSL levels under the tested conditions. Surprisingly, targeted disruptions of hacA alone and hacA and hacB together confer complementable phenotypes that are very similar to autoaggregative phenotypes seen in other species. While AHL acylases might enable P. syringae B728a to degrade signals of competing species and block expression of their QS-dependent traits, these enzymes also play fundamental roles in biofilm formation.


2002 ◽  
Vol 184 (23) ◽  
pp. 6515-6521 ◽  
Author(s):  
Amy L. Schaefer ◽  
Terumi A. Taylor ◽  
J. Thomas Beatty ◽  
E. P. Greenberg

ABSTRACT Many proteobacteria use acyl-homoserine lactones as quorum-sensing signals. Traditionally, biological detection systems have been used to identify bacteria that produce acyl-homoserine lactones, although the specificities of these detection systems can limit discovery. We used a sensitive approach that did not require a bioassay to detect production of long-acyl-chain homoserine lactone production by Rhodobacter capsulatus and Paracoccus denitrificans. These long-chain acyl-homoserine lactones are not readily detected by standard bioassays. The most abundant acyl-homoserine lactone was N-hexadecanoyl-homoserine lactone. The long-chain acyl-homoserine lactones were concentrated in cells but were also found in the culture fluid. An R. capsulatus gene responsible for long-chain acyl-homoserine lactone synthesis was identified. A mutation in this gene, which we named gtaI, resulted in decreased production of the R. capsulatus gene transfer agent, and gene transfer agent production was restored by exogenous addition of N-hexadecanoyl-homoserine lactone. Thus, long-chain acyl-homoserine lactones serve as quorum-sensing signals to enhance genetic exchange in R. capsulatus.


1999 ◽  
Vol 181 (12) ◽  
pp. 3816-3823 ◽  
Author(s):  
Belen Rodelas ◽  
James K. Lithgow ◽  
Florence Wisniewski-Dye ◽  
Andrea Hardman ◽  
Adam Wilkinson ◽  
...  

ABSTRACT The rhi genes of Rhizobium leguminosarumbiovar viciae are expressed in the rhizosphere and play a role in the interaction with legumes, such as the pea. Previously (K. M. Gray, J. P. Pearson, J. A. Downie, B. E. A. Boboye, and E. P. Greenberg, J. Bacteriol. 178:372–376, 1996) therhiABC operon had been shown to be regulated by RhiR and to be induced by addedN-(3-hydroxy-7-cis-tetradecenoyl)-l-homoserine lactone (3OH,C14:1-HSL). Mutagenesis of a cosmid carrying the rhiABC and rhiR gene region identified a gene (rhiI) that affects the level of rhiAexpression. Mutation of rhiI slightly increased the number of nodules formed on the pea. The rhiI gene is (likerhiA) regulated by rhiR in a cell density-dependent manner. RhiI is similar to LuxI and other proteins involved in the synthesis of N-acyl-homoserine lactones (AHLs). Chemical analyses of spent culture supernatants demonstrated that RhiI produces N-(hexanoyl)-l-homoserine lactone (C6-HSL) andN-(octanoyl)-l-homoserine lactone (C8-HSL). Both of these AHLs induced rhiA-lacZand rhiI-lacZ expression on plasmids introduced into anAgrobacterium strain that produces no AHLs, showing thatrhiI is positively regulated by autoinduction. However, in this system no induction of rhiA or rhiI with 3OH,C14:1-HSL was observed. Analysis of the spent culture supernatant of the wild-type R. leguminosarum bv. viciae revealed that at least seven different AHLs are made. Mutation ofrhiI decreased the amounts of C6-HSL and C8-HSL but did not block their formation, and in this background the rhiI mutation did not significantly affect the expression levels of the rhiI gene orrhiABC genes or the accumulation of RhiA protein. These observations suggest that there are additional loci involved in AHL production in R. leguminosarum bv. viciae and that they affect rhiI and rhiABC expression. We postulate that the previously observed induction of rhiA by 3OH,C14:1-HSL may be due to an indirect effect caused by induction of other AHL production loci.


2006 ◽  
Vol 74 (10) ◽  
pp. 5687-5692 ◽  
Author(s):  
Sabine Zimmermann ◽  
Christof Wagner ◽  
Wencke Müller ◽  
Gerald Brenner-Weiss ◽  
Friederike Hug ◽  
...  

ABSTRACT Acyl homoserine lactones are synthesized by Pseudomonas aeruginosa as signaling molecules which control production of virulence factors and biofilm formation in a paracrine manner. We found that N-(3-oxododecanoyl)-l-homoserine lactone (3OC12-HSL), but not its 3-deoxo isomer or acyl-homoserine lactones with shorter fatty acids, induced the directed migration (chemotaxis) of human polymorphonuclear neutrophils (PMN) in vitro. By use of selective inhibitors a signaling pathway, comprising phosphotyrosine kinases, phospholipase C, protein kinase C, and mitogen-activated protein kinase C, could be delineated. In contrast to the well-studied chemokines complement C5a and interleukin 8, the chemotaxis did not depend on pertussis toxin-sensitive G proteins, indicating that 3OC12-HSL uses another signaling pathway. Strong evidence for the presence of a receptor for 3OC12-HSL on PMN was derived from uptake studies; by use of radiolabeled 3OC12-HSL, specific and saturable binding to PMN was seen. Taken together, our data provide evidence that PMN recognize and migrate toward a source of 3OC12-HSL (that is, to the site of a developing biofilm). We propose that this early attraction of PMN could contribute to prevention of biofilm formation.


2020 ◽  
Vol 8 (19) ◽  
pp. 4228-4236
Author(s):  
Sahana Vasudevan ◽  
Parthasarathy Srinivasan ◽  
John Bosco Balaguru Rayappan ◽  
Adline Princy Solomon

We report a PL biosensor using cysteamine functionalized ZnO nanoparticles for the detection of quorum sensing signals (N-acyl homoserine lactones).


2012 ◽  
Vol 25 (5) ◽  
pp. 677-683 ◽  
Author(s):  
Fang Liu ◽  
Ziriu Bian ◽  
Zhenhua Jia ◽  
Qian Zhao ◽  
Shuishan Song

Many gram-negative bacteria use N-acyl-homoserine lactones (AHL) as quorum-sensing signals to coordinate their collective behaviors. Accumulating evidence indicates that plants can respond to AHL. However, little is known about the molecular mechanism of plants reacting to these bacterial signals. In this study, we show that the treatment of Arabidopsis roots with N-3-oxo-hexanoyl-homoserine lactone (3OC6-HSL) and N-3-oxo-octanoyl-homoserine lactone (3OC8-HSL) resulted in significant root elongation. The genetic analysis revealed that the T-DNA insertional mutants of gcr1, encoding a G-protein-coupled receptor GCR1, were insensitive to 3OC6-HSL or 3OC8-HSL in assays of root growth. The loss-of-function mutants of the sole canonical Gα subunit GPA1 showed no response to AHL promotion of root elongation whereas Gα gain-of-function plants overexpressing either the wild type or a constitutively active version of Arabidopsis Gα exhibited the exaggerated effect on root elongation caused by AHL. Furthermore, the expression of GCR1 and GPA1 were significantly upregulated after plants were contacted with both AHL. Taken together, our results suggest that GCR1 and GPA1 are involved in AHL-mediated elongation of Arabidopsis roots. This provides insight into the mechanism of plant responses to bacterial quorum-sensing signals.


2007 ◽  
Vol 73 (11) ◽  
pp. 3724-3727 ◽  
Author(s):  
Kristen M. DeAngelis ◽  
Mary K. Firestone ◽  
Steven E. Lindow

ABSTRACT To investigate quorum sensing in rhizosphere soil, a whole-cell biosensor, Agrobacterium tumefaciens(pAHL-Ice), was constructed. The biosensor responded to all N-acyl homoserine lactones (AHLs) tested, except C4 homoserine lactone, with a minimum detection limit of 10−12 M, as well as to both exogenously added AHLs and AHL-producing bacterial strains in soil. This highly sensitive biosensor reveals for the first time the increased AHL availability in intact rhizosphere microbial communities compared to that in bulk soil.


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