scholarly journals Are There Acyl-Homoserine Lactones within Mammalian Intestines?

2012 ◽  
Vol 195 (2) ◽  
pp. 173-179 ◽  
Author(s):  
Matthew C. Swearingen ◽  
Anice Sabag-Daigle ◽  
Brian M. M. Ahmer
Keyword(s):  
Quorum Sensing ◽  
Intestinal Tract ◽  
Homoserine Lactone ◽  
Signaling Molecules ◽  
Content Type ◽  
Homoserine Lactones ◽  
Luxr Homolog ◽  
Intestinal Pathogens ◽  
Mammalian Intestine ◽  
Surprising Finding

ABSTRACTManyProteobacteriaare capable of quorum sensing usingN-acyl-homoserine lactone (acyl-HSL) signaling molecules that are synthesized by LuxI or LuxM homologs and detected by transcription factors of the LuxR family. Most quorum-sensing species have at least one LuxR and one LuxI homolog. However, members of theEscherichia,Salmonella,Klebsiella, andEnterobactergenera possess only a single LuxR homolog, SdiA, and no acyl-HSL synthase. The most obvious hypothesis is that these organisms are eavesdropping on acyl-HSL production within the complex microbial communities of the mammalian intestinal tract. However, there is currently no evidence of acyl-HSLs being produced within normal intestinal communities. A few intestinal pathogens, includingYersinia enterocolitica, do produce acyl-HSLs, andSalmonellacan detect them during infection. Therefore, a more refined hypothesis is that SdiA orthologs are used for eavesdropping on other quorum-sensing pathogens in the host. However, the lack of acyl-HSL signaling among the normal intestinal residents is a surprising finding given the complexity of intestinal communities. In this review, we examine the evidence for and against the possibility of acyl-HSL signaling molecules in the mammalian intestine and discuss the possibility that related signaling molecules might be present and awaiting discovery.

scholarly journals Virulence of Burkholderia mallei Quorum-Sensing Mutants

2013 ◽  
Vol 81 (5) ◽  
pp. 1471-1478 ◽  
Author(s):  
Charlotte Majerczyk ◽  
Loren Kinman ◽  
Tony Han ◽  
Richard Bunt ◽  
E. Peter Greenberg
Keyword(s):  
Quorum Sensing ◽  
Homoserine Lactone ◽  
Mouse Lung ◽  
Depth Information ◽  
Acyl Homoserine Lactone ◽  
Burkholderia Mallei ◽  
Content Type ◽  
Homoserine Lactones ◽  
Acyl Homoserine Lactones

ABSTRACTManyProteobacteriause acyl-homoserine lactone-mediated quorum-sensing (QS) to activate specific sets of genes as a function of cell density. QS often controls the virulence of pathogenic species, and in fact a previous study indicated that QS was important forBurkholderia malleimouse lung infections. To gain in-depth information on the role of QS inB. malleivirulence, we constructed and characterized a mutant ofB. malleistrain GB8 that was unable to make acyl-homoserine lactones. The QS mutant showed virulence equal to that of its wild-type parent in an aerosol mouse infection model, and growth in macrophages was indistinguishable from that of the parent strain. Furthermore, we assessed the role of QS inB. malleiATCC 23344 by constructing and characterizing a mutant strain producing AiiA, a lactonase enzyme that degrades acyl-homoserine lactones. Although acyl-homoserine lactone levels in cultures of this strain are very low, it showed full virulence. Contrary to the previous report, we conclude that QS is not required for acuteB. malleiinfections of mice. QS may be involved in some stage of chronic infections in the natural host of horses, or the QS genes may be remnants of the QS network inB. pseudomalleifrom which this host-adapted pathogen evolved.

scholarly journals A Burkholderia thailandensis Acyl-Homoserine Lactone-Independent Orphan LuxR Homolog That Activates Production of the Cytotoxin Malleilactone

2015 ◽  
Vol 197 (21) ◽  
pp. 3456-3462 ◽  
Author(s):  
Thao T. Truong ◽  
Mohammad Seyedsayamdost ◽  
E. Peter Greenberg ◽  
Josephine R. Chandler
Keyword(s):  
Transcription Factors ◽  
Quorum Sensing ◽  
Gene Cluster ◽  
Homoserine Lactone ◽  
Acyl Homoserine Lactone ◽  
Burkholderia Thailandensis ◽  
Content Type ◽  
Laboratory Conditions ◽  
Luxr Homolog ◽  
Normal Laboratory

ABSTRACTBurkholderia thailandensishas three acyl-homoserine lactone (AHL) LuxR-LuxI quorum-sensing circuits and two orphan LuxR homologs. Orphans are LuxR-type transcription factors that do not have cognate LuxI-type AHL synthases. One of the orphans, MalR, is genetically linked to themalgene cluster, which encodes enzymes required for production of the cytotoxic polyketide malleilactone. Under normal laboratory conditions themalgene cluster is silent; however, antibiotics like trimethoprim inducemaltranscription. We show that trimethoprim-dependent induction of themalgenes requires MalR. MalR has all of the conserved amino acid residues characteristic of AHL-responsive LuxR homologs, but inB. thailandensis, MalR activation of malleilactone synthesis genes is not responsive to AHLs. MalR can activate transcription from themalpromoter inE. coliwithout addition of AHLs or trimethoprim. Expression ofmalRinB. thailandensisis induced by trimethoprim. Our data indicate that MalR binds to aluxbox-like element in themalpromoter and activates transcription of themalgenes in an AHL-independent manner. Antibiotics like trimethoprim appear to activatemalgene expression indirectly by somehow activatingmalRexpression. MalR activation of themalgenes represents an example of a LuxR homolog that is not a receptor for an AHL quorum-sensing signal. Our evidence is consistent with the idea thatmalgene activation depends solely on sufficient transcription of themalRgene.IMPORTANCELuxR proteins are transcription factors that are typically activated by acyl-homoserine lactone (AHL) signals. We demonstrate that a conserved LuxR family protein, MalR, activates genes independently of AHLs. MalR is required for transcription of genes coding for synthesis of the cytotoxic polyketide malleilactone. These genes are not expressed when cells are grown under normal laboratory conditions. In laboratory culture, MalR induction of malleilactone requires certain antibiotics, such as trimethoprim, which increasemalRexpression by an unknown mechanism. At sufficient levels ofmalRexpression, MalR functions independently of any external signal. Our findings show that MalR is an activator of the silent malleilactone biosynthesis genes and that MalR functions independently of AHLs.

scholarly journals LuxR- and LuxI-Type Quorum-Sensing Circuits Are Prevalent in Members of the Populus deltoides Microbiome

2013 ◽  
Vol 79 (18) ◽  
pp. 5745-5752 ◽  
Author(s):  
Amy L. Schaefer ◽  
Colin R. Lappala ◽  
Ryan P. Morlen ◽  
Dale A. Pelletier ◽  
Tse-Yuan S. Lu ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Populus Deltoides ◽  
Cell Communication ◽  
Homoserine Lactone ◽  
Bacterial Isolates ◽  
Content Type ◽  
Eastern Cottonwood ◽  
Bacterial Signaling ◽  
Signal Production ◽  
Plant Signals

ABSTRACTWe are interested in the root microbiome of the fast-growing Eastern cottonwood tree,Populus deltoides. There is a large bank of bacterial isolates fromP. deltoides, and there are 44 draft genomes of bacterial endophyte and rhizosphere isolates. As a first step in efforts to understand the roles of bacterial communication and plant-bacterial signaling inP. deltoides, we focused on the prevalence of acyl-homoserine lactone (AHL) quorum-sensing-signal production and reception in members of theP. deltoidesmicrobiome. We screened 129 bacterial isolates for AHL production using a broad-spectrum bioassay that responds to many but not all AHLs, and we queried the available genome sequences of microbiome isolates for homologs of AHL synthase and receptor genes. AHL signal production was detected in 40% of 129 strains tested. Positive isolates included members of theAlpha-,Beta-, andGammaproteobacteria. Members of theluxIfamily of AHL synthases were identified in 18 of 39 proteobacterial genomes, including genomes of some isolates that tested negative in the bioassay. Members of theluxRfamily of transcription factors, which includes AHL-responsive factors, were more abundant thanluxIhomologs. There were 72 in the 39 proteobacterial genomes. Some of theluxRhomologs appear to be members of a subfamily of LuxRs that respond to as-yet-unknown plant signals rather than bacterial AHLs. Apparently, there is a substantial capacity for AHL cell-to-cell communication in proteobacteria of theP. deltoidesmicrobiota, and there are alsoProteobacteriawith LuxR homologs of the type hypothesized to respond to plant signals or cues.

scholarly journals The Quorum-Sensing Molecules Farnesol/Homoserine Lactone and Dodecanol Operate via Distinct Modes of Action in Candida albicans

2011 ◽  
Vol 10 (8) ◽  
pp. 1034-1042 ◽  
Author(s):  
Rebecca A. Hall ◽  
Kara J. Turner ◽  
James Chaloupka ◽  
Fabien Cottier ◽  
Luisa De Sordi ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Quorum Sensing ◽  
Signaling Pathway ◽  
Homoserine Lactone ◽  
Burkholderia Cenocepacia ◽  
Camp Signaling ◽  
Mammalian Host ◽  
Content Type ◽  
Hyphal Development ◽  
Natural Flora

ABSTRACTLiving as a commensal,Candida albicansmust adapt and respond to environmental cues generated by the mammalian host and by microbes comprising the natural flora. These signals have opposing effects onC. albicans, with host cues promoting the yeast-to-hyphal transition and bacteria-derived quorum-sensing molecules inhibiting hyphal development. Hyphal development is regulated through modulation of the cyclic AMP (cAMP)/protein kinase A (PKA) signaling pathway, and it has been postulated that quorum-sensing molecules can affect filamentation by inhibiting the cAMP pathway. Here, we show that both farnesol and 3-oxo-C12-homoserine lactone, a quorum-sensing molecule secreted byPseudomonas aeruginosa, block hyphal development by affecting cAMP signaling; they both directly inhibited the activity of theCandidaadenylyl cyclase, Cyr1p. In contrast, the 12-carbon alcohol dodecanol appeared to modulate hyphal development and the cAMP signaling pathway without directly affecting the activity of Cyr1p. Instead, we show that dodecanol exerted its effects through a mechanism involving theC. albicanshyphal repressor, Sfl1p. Deletion ofSFL1did not affect the response to farnesol but did interfere with the response to dodecanol. Therefore, quorum sensing inC. albicansis mediated via multiple mechanisms of action. Interestingly, our experiments raise the possibility that theBurkholderia cenocepaciadiffusible signal factor, BDSF, also mediates its effects via Sfl1p, suggesting that dodecanol's mode of action, but not farnesol or 3-oxo-C12-homoserine lactone, may be used by other quorum-sensing molecules.

scholarly journals Disruption of Quorum Sensing and Virulence inBurkholderia cenocepaciaby a Structural Analogue of thecis-2-Dodecenoic Acid Signal

2019 ◽  
Vol 85 (8) ◽  
Author(s):  
Chaoyu Cui ◽  
Shihao Song ◽  
Chunxi Yang ◽  
Xiuyun Sun ◽  
Yutong Huang ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Bacterial Infections ◽  
Opportunistic Pathogen ◽  
Homoserine Lactone ◽  
Burkholderia Cenocepacia ◽  
Enoic Acid ◽  
Acyl Homoserine Lactone ◽  
Structural Analogue ◽  
Content Type ◽  
Signal Production

ABSTRACTQuorum sensing (QS) signals are widely used by bacterial pathogens to control biological functions and virulence in response to changes in cell population densities.Burkholderia cenocepaciaemploys a molecular mechanism in which thecis-2-dodecenoic acid (namedBurkholderiadiffusiblesignalfactor [BDSF]) QS system regulatesN-acyl homoserine lactone (AHL) signal production and virulence by modulating intracellular levels of cyclic diguanosine monophosphate (c-di-GMP). Thus, inhibition of BDSF signaling may offer a non-antibiotic-based therapeutic strategy against BDSF-regulated bacterial infections. In this study, we report the synthesis of small-molecule mimics of the BDSF signal and evaluate their ability to inhibit BDSF QS signaling inB. cenocepacia. A novel structural analogue of BDSF, 14-Me-C16:Δ2(cis-14-methylpentadec-2-enoic acid), was observed to inhibit BDSF production and impair BDSF-regulated phenotypes inB. cenocepacia, including motility, biofilm formation, and virulence, while it did not inhibit the growth rate of this pathogen. 14-Me-C16:Δ2also reduced AHL signal production. Genetic and biochemical analyses showed that 14-Me-C16:Δ2inhibited the production of the BDSF and AHL signals by decreasing the expression of their synthase-encoding genes. Notably, 14-Me-C16:Δ2attenuated BDSF-regulated phenotypes in variousBurkholderiaspecies. These findings suggest that 14-Me-C16:Δ2could potentially be developed as a new therapeutic agent against pathogenicBurkholderiaspecies by interfering with their QS signaling.IMPORTANCEBurkholderia cenocepaciais an important opportunistic pathogen which can cause life-threatening infections in susceptible individuals, particularly in cystic fibrosis and immunocompromised patients. It usually employs two types of quorum sensing (QS) systems, including thecis-2-dodecenoic acid (BDSF) system andN-acyl homoserine lactone (AHL) system, to regulate virulence. In this study, we have designed and identified an unsaturated fatty acid compound (cis-14-methylpentadec-2-enoic acid [14-Me-C16:Δ2]) that is capable of interfering withB. cenocepaciaQS signaling and virulence. We demonstrate that 14-Me-C16:Δ2reduced BDSF and AHL signal production inB. cenocepacia. It also impaired QS-regulated phenotypes in variousBurkholderiaspecies. These results suggest that 14-Me-C16:Δ2could interfere with QS signaling in manyBurkholderiaspecies and might be developed as a new antibacterial agent.

Close-up on a bacterial informational war in the geocaulosphere

2020 ◽  
Vol 66 (7) ◽  
pp. 447-454 ◽  
Author(s):  
Andrea Chane ◽  
Yvann Bourigault ◽  
Mathilde Bouteiller ◽  
Yoan Konto-Ghiorghi ◽  
Annabelle Merieau ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Communication Systems ◽  
Cell Communication ◽  
Soft Rot ◽  
Homoserine Lactone ◽  
Signaling Molecules ◽  
Disease Symptoms ◽  
Reporter Strains ◽  
Bright Green ◽  
Bright Green Fluorescence

The geocaulosphere is home to microbes that establish communication between themselves and others that disrupt them. These cell-to-cell communication systems are based on the synthesis and perception of signaling molecules, of which the best known belong to the N-acyl-homoserine lactone (AHL) family. Among indigenous bacteria, certain Gram-positive actinobacteria can sense AHLs produced by soft-rot Gram-negative phytopathogens and can degrade the quorum-sensing AHL signals to impair the expression of virulence factors. We mimicked this interaction by introducing dual-color reporter strains suitable for monitoring both the location of the cells and their quorum-sensing and -quenching activities, in potato tubers. The exchange of AHL signals within the pathogen’s cell quorum was clearly detected by the presence of bright green fluorescence instead of blue in a portion of Pectobacterium-tagged cells. This phenomenon in Rhodococcus cells was accompanied by a change from red fluorescence to orange, showing that the disappearance of signaling molecules is due to rhodococcal AHL degradation rather than the inhibition of AHL production. Rhodococci are victorious in this fight for the control of AHL-based communication, as their jamming activity is powerful enough to prevent the onset of disease symptoms.

scholarly journals Alginate Oligosaccharide-Induced Modification of the lasI-lasR and rhlI-rhlR Quorum-Sensing Systems in Pseudomonas aeruginosa

2018 ◽  
Vol 62 (5) ◽  
Author(s):  
Alison A. Jack ◽  
Saira Khan ◽  
Lydia C. Powell ◽  
Manon F. Pritchard ◽  
Konrad Beck ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Laser Scanning ◽  
Homoserine Lactone ◽  
Laser Scanning Microscopy ◽  
Extracellular Dna ◽  
Mass Spectrometry Analysis ◽  
Confocal Laser ◽  
Steric Interaction ◽  
Content Type

ABSTRACT Pseudomonas aeruginosa plays a major role in many chronic infections. Its ability to readily form biofilms contributes to its success as an opportunistic pathogen and its resistance/tolerance to antimicrobial/antibiotic therapy. A low-molecular-weight alginate oligomer (OligoG CF-5/20) derived from marine algae has previously been shown to impair motility in P. aeruginosa biofilms and disrupt pseudomonal biofilm assembly. As these bacterial phenotypes are regulated by quorum sensing (QS), we hypothesized that OligoG CF-5/20 may induce alterations in QS signaling in P. aeruginosa . QS regulation was studied by using Chromobacterium violaceum CV026 biosensor assays that showed a significant reduction in acyl homoserine lactone (AHL) production following OligoG CF-5/20 treatment (≥2%; P < 0.05). This effect was confirmed by liquid chromatography-mass spectrometry analysis of C 4 -AHL and 3-oxo-C 12 -AHL production (≥2%; P < 0.05). Moreover, quantitative PCR showed that reduced expression of both the las and rhl systems was induced following 24 h of treatment with OligoG CF-5/20 (≥0.2%; P < 0.05). Circular dichroism spectroscopy indicated that these alterations were not due to steric interaction between the AHL and OligoG CF-5/20. Confocal laser scanning microscopy (CLSM) and COMSTAT image analysis demonstrated that OligoG CF-5/20-treated biofilms had a dose-dependent decrease in biomass that was associated with inhibition of extracellular DNA synthesis (≥0.5%; P < 0.05). These changes correlated with alterations in the extracellular production of the pseudomonal virulence factors pyocyanin, rhamnolipids, elastase, and total protease ( P < 0.05). The ability of OligoG CF-5/20 to modify QS signaling in P. aeruginosa PAO1 may influence critical downstream functions such as virulence factor production and biofilm formation.

scholarly journals Quorum Sensing Signal Selectivity and the Potential for Interspecies Cross Talk

mBio ◽  
2019 ◽  
Vol 10 (2) ◽  
Author(s):  
Samantha Wellington ◽  
E. Peter Greenberg
Keyword(s):  
Quorum Sensing ◽  
Cell Signaling ◽  
Cross Talk ◽  
Homoserine Lactone ◽  
Interspecies Interactions ◽  
Interspecies Competition ◽  
Content Type ◽  
E Coli ◽  
Competition And Cooperation ◽  
Wide Range

ABSTRACTMany species of proteobacteria communicate with kin and coordinate group behaviors through a form of cell-cell signaling called acyl-homoserine lactone (AHL) quorum sensing (QS). Most AHL receptors are thought to be specific for their cognate signal, ensuring that bacteria cooperate and share resources only with closely related kin cells. Although specificity is considered fundamental to QS, there are reports of “promiscuous” receptors that respond broadly to nonself signals. These promiscuous responses expand the function of QS systems to include interspecies interactions and have been implicated in both interspecies competition and cooperation. Because bacteria are frequently members of polymicrobial communities, AHL cross talk between species could have profound impacts. To better understand the prevalence of QS promiscuity, we measured the activity of seven QS receptors in their native host organisms. To facilitate comparison of our results to previous studies, we also measured receptor activity using heterologous expression inEscherichia coli. We found that the standardE. colimethods consistently overestimate receptor promiscuity and sensitivity and that overexpression of the receptors is sufficient to account for the discrepancy between native andE. colireporters. Additionally, receptor overexpression resulted in AHL-independent activity inPseudomonas aeruginosa. Using our activation data, we developed a quantitative score of receptor selectivity. We find that the receptors display a wide range of selectivity and that most receptors respond sensitively and strongly to at least one nonself signal, suggesting a broad potential for cross talk between QS systems.IMPORTANCESpecific recognition of cognate signals is considered fundamental to cell signaling circuits as it creates fidelity in the communication system. In bacterial quorum sensing (QS), receptor specificity ensures that bacteria cooperate only with kin. There are examples, however, of QS receptors that respond promiscuously to multiple signals. “Eavesdropping” by these promiscuous receptors can be beneficial in both interspecies competition and cooperation. Despite their potential significance, we know little about the prevalence of promiscuous QS receptors. Further, many studies rely on methods requiring receptor overexpression, which is known to increase apparent promiscuity. By systematically studying QS receptors in their natural parent strains, we find that the receptors display a wide range of selectivity and that there is potential for significant cross talk between QS systems. Our results provide a basis for hypotheses about the evolution and function of promiscuous signal receptors and for predictions about interspecies interactions in complex microbial communities.

scholarly journals A rhlI 5′ UTR-Derived sRNA Regulates RhlR-Dependent Quorum Sensing in Pseudomonas aeruginosa

mBio ◽  
2019 ◽  
Vol 10 (5) ◽  
Author(s):  
Maureen K. Thomason ◽  
Maya Voichek ◽  
Daniel Dar ◽  
Victoria Addis ◽  
David Fitzgerald ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Homoserine Lactone ◽  
Regulatory Elements ◽  
Content Type ◽  
Reading Frame ◽  
Bacterial Physiology ◽  
Small Regulatory Rna ◽  
Key Enzyme ◽  
Opportunistic Human Pathogen

ABSTRACT N-Acyl homoserine lactone (AHL) quorum sensing (QS) controls expression of over 200 genes in Pseudomonas aeruginosa. There are two AHL regulatory systems: the LasR-LasI circuit and the RhlR-RhlI system. We mapped transcription termination sites affected by AHL QS in P. aeruginosa, and in doing so we identified AHL-regulated small RNAs (sRNAs). Of interest, we noted that one particular sRNA was located within the rhlI locus. We found that rhlI, which encodes the enzyme that produces the AHL N-butanoyl-homoserine lactone (C4-HSL), is controlled by a 5′ untranslated region (UTR)-derived sRNA we name RhlS. We also identified an antisense RNA encoded opposite the beginning of the rhlI open reading frame, which we name asRhlS. RhlS accumulates as wild-type cells enter stationary phase and is required for the production of normal levels of C4-HSL through activation of rhlI translation. RhlS also directly posttranscriptionally regulates at least one other unlinked gene, fpvA. The asRhlS appears to be expressed at maximal levels during logarithmic growth, and we suggest RhlS may act antagonistically to the asRhlS to regulate rhlI translation. The rhlI-encoded sRNAs represent a novel aspect of RNA-mediated tuning of P. aeruginosa QS. IMPORTANCE The opportunistic human pathogen Pseudomonas aeruginosa possesses multiple quorum sensing systems that regulate and coordinate production of virulence factors and adaptation to different environments. Despite extensive research, the regulatory elements that play a role in this complex network are still not fully understood. By using several RNA sequencing techniques, we were able to identify a small regulatory RNA we named RhlS. RhlS increases translation of RhlI, a key enzyme in the quorum sensing pathway, and represses the fpvA mRNA encoding one of the siderophore pyoverdine receptors. Our results highlight a new regulatory layer of P. aeruginosa quorum sensing and contribute to the growing understanding of the role regulatory RNAs play in bacterial physiology.

scholarly journals Distribution of Quorum-Sensing Genes in the Burkholderia cepacia Complex

2001 ◽  
Vol 69 (7) ◽  
pp. 4661-4666 ◽  
Author(s):  
E. Lutter ◽  
S. Lewenza ◽  
J. J. Dennis ◽  
M. B. Visser ◽  
P. A. Sokol
Keyword(s):  
Quorum Sensing ◽  
Burkholderia Cepacia ◽  
Homoserine Lactone ◽  
Burkholderia Cepacia Complex ◽  
Homoserine Lactones

ABSTRACT The distribution of quorum-sensing genes among strains from seven genomovars of the Burkholderia cepaciacomplex was examined by PCR. cepR and cepI were amplified from B. cepacia genomovars I and III, B. stabilis, and B. vietnamiensis. cepR was also amplified from B. multivorans and B. cepacia genomovar VI. bviIR were amplified from B. vietnamiensis. All genomovars producedN-octanoyl-l-homoserine lactone andN-hexanoyl-l-homoserine lactone.B. vietnamiensis and B. cepacia genomovar VII produced additional N-acyl-l-homoserine lactones.

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