scholarly journals Environmental modification via a quorum sensing molecule influences the social landscape of siderophore production

2017 ◽  
Vol 284 (1852) ◽  
pp. 20170200 ◽  
Author(s):  
Roman Popat ◽  
Freya Harrison ◽  
Ana C. da Silva ◽  
Scott A. S. Easton ◽  
Luke McNally ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Public Goods ◽  
Bacterial Species ◽  
Relative Fitness ◽  
Iron Starvation ◽  
Signal Molecule ◽  
Signalling Molecules ◽  
Signalling Molecule ◽  
The Impact ◽  
Social Trait

Bacteria produce a wide variety of exoproducts that favourably modify their environment and increase their fitness. These are often termed ‘public goods’ because they are costly for individuals to produce and can be exploited by non-producers (cheats). The outcome of conflict over public goods is dependent upon the prevailing environment and the phenotype of the individuals in competition. Many bacterial species use quorum sensing (QS) signalling molecules to regulate the production of public goods. QS, therefore, determines the cooperative phenotype of individuals, and influences conflict over public goods. In addition to their regulatory functions, many QS molecules have additional properties that directly modify the prevailing environment. This leads to the possibility that QS molecules could influence conflict over public goods indirectly through non-signalling effects, and the impact of this on social competition has not previously been explored. The Pseudomonas aeruginosa QS signal molecule PQS is a powerful chelator of iron which can cause an iron starvation response. Here, we show that PQS stimulates a concentration-dependent increase in the cooperative production of iron scavenging siderophores, resulting in an increase in the relative fitness of non-producing siderophore cheats. This is likely due to an increased cost of siderophore output by producing cells and a concurrent increase in the shared benefits, which accrue to both producers and cheats. Although PQS can be a beneficial signalling molecule for P. aeruginosa , our data suggest that it can also render a siderophore-producing population vulnerable to competition from cheating strains. More generally, our results indicate that the production of one social trait can indirectly affect the costs and benefits of another social trait.

scholarly journals Environmental modification via a quorum sensing molecule influences the social landscape of siderophore production

2016 ◽  
Author(s):  
Roman Popat ◽  
Freya Harrison ◽  
Ana C. da Silva ◽  
Scott A. S. Easton ◽  
Luke McNally ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Public Goods ◽  
Bacterial Species ◽  
Relative Fitness ◽  
Iron Starvation ◽  
Signal Molecule ◽  
Signalling Molecules ◽  
Signalling Molecule ◽  
The Impact ◽  
Social Trait

Bacteria produce a wide variety of exoproducts that favourably modify their environment and increase their fitness. These are often termed ‘public goods’ because they are costly for individuals to produce and can be exploited by non-producers (‘cheats’). The outcome of conflict over public goods is dependent upon the prevailing environment and the phenotype of the individuals in competition. Many bacterial species use quorum sensing (QS) signalling molecules to regulate the production of public goods. QS therefore determines the cooperative phenotype of individuals, and influences conflict over public goods. In addition to their regulatory functions, many QS molecules have additional properties that directly modify the prevailing environment. This leads to the possibility that QS molecules could influence conflict over public goods indirectly through nonsignalling effects, and the impact of this on social competition has not previously been explored. ThePseudomonas aeruginosaQS signal molecule PQS is a powerful chelator of iron which can cause an iron starvation response. Here we show that PQS stimulates a concentration-dependent increase in the cooperative production of iron scavenging siderophores, resulting in an increase in the relative fitness of non-producing siderophore cheats. This is likely due to an increased cost of siderophore output by producing cells and a concurrent increase in the shared benefits, which accrue to both producers and cheats. Although PQS can be a beneficial signalling molecule forP. aeruginosa, our data suggests that it can also render a siderophore-producing population vulnerable to competition from cheating strains. More generally our results indicate that the production of one social trait can indirectly affect the costs and benefits of another social trait.

Loss of RND-type multidrug efflux pumps triggers iron starvation and lipid A modifications in Pseudomonas aeruginosa

2021 ◽  
Author(s):  
Justyna W. Adamiak ◽  
Varsha Jhawar ◽  
Vincent Bonifay ◽  
Courtney E. Chandler ◽  
Inga V. Leus ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Lipid A ◽  
Cell Envelope ◽  
Iron Acquisition ◽  
Bacterial Species ◽  
Transport Systems ◽  
Permeability Barrier ◽  
Iron Starvation ◽  
Analytical Approaches

Transporters belonging to the Resistance-Nodulation-Division (RND) superfamily of proteins are invariably present in the genomes of Gram-negative bacteria and are largely responsible for the intrinsic antibiotic resistance of these organisms. The number of genes encoding RND transporters per genome vary from one to sixteen and correlates with environmental versatilities of bacterial species. Pseudomonas aeruginosa PAO1 strain, a ubiquitous nosocomial pathogen, possesses twelve RND pumps, which are implicated in development of clinical multidrug resistance and known to contribute to virulence, quorum sensing and many other physiological functions. In this study, we analyzed how P. aeruginosa physiology adapts to the lack of RND-mediated efflux activities. A combination of transcriptomics, metabolomics, genetic and analytical approaches showed that the P. aeruginosa PΔ6 strain lacking six best characterized RND pumps activates a specific adaptation response that involves significant changes in abundance and activities of several transport systems, quorum sensing, iron acquisition and lipid A modifications. Our results demonstrate that these cells accumulate large quantities of pseudomonas quorum signal (PQS), which triggers iron starvation and activation of siderophore biosynthesis and acquisition pathways. The accumulation of iron in turn activates lipid A modification and membrane protection pathways. A transcriptionally regulated RND pump MuxABC-OpmB contributes to these transformations by controlling concentrations of coumarins. Our results suggest that these changes reduce the permeability barrier of the outer membrane and are needed to protect the cell envelope of efflux-deficient P. aeruginosa .

scholarly journals Indole Reverses Intrinsic Antibiotic Resistance by Activating a Novel Dual-Function Importer

mBio ◽  
2019 ◽  
Vol 10 (3) ◽  
Author(s):  
Yan Wang ◽  
Tian Tian ◽  
Jingjing Zhang ◽  
Xin Jin ◽  
Huan Yue ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Quorum Sensing ◽  
Bacterial Species ◽  
Signaling Molecules ◽  
Dual Function ◽  
Vitamin B ◽  
Signal Molecule ◽  
Dynamic Regulation ◽  
Bacterial Antibiotic Resistance ◽  
Dependent Behavior

ABSTRACT Bacterial antibiotic resistance modulation by small signaling molecules is an emerging mechanism that has been increasingly reported in recent years. Several studies indicate that indole, an interkingdom signaling molecule, increases bacterial antibiotic resistance. However, the mechanism through which indole reduces antibiotic resistance is largely unknown. In this study, we demonstrated a novel mechanism for indole-mediated reversal of intrinsic antibiotic resistance in Lysobacter. This reversal was facilitated by a novel BtuD-associated dual-function importer that can transfer both vitamin B12 and antibiotics. Indole stimulated btuD overexpression and promoted efficient absorption of extracellular vitamin B12; meanwhile, the weak selectivity of the importer caused cells to take up excessive doses of antibiotics that resulted in cell death. Consistently, btuD deletion and G48Y/K49D substitution led to marked reductions in the uptake of both antibiotics and vitamin B12. This novel mechanism is common across multiple bacterial species, among which the Q-loop amino acid of BtuD proteins is Glu (E) instead of Gln (Q). Interestingly, the antibiotic resistance of Lysobacter spp. can be restored by another small quorum sensing signaling factor, 13-methyltetradecanoic acid, designated LeDSF, in response to bacterial population density. This work highlights the mechanisms underlying dynamic regulation of bacterial antibiotic resistance by small signaling molecules and suggests that the effectiveness of traditional antibiotics could be increased by coupling them with appropriate signaling molecules. IMPORTANCE Recently, signaling molecules were found to play a role in mediating antibiotic resistance. In this study, we demonstrated that indole reversed the intrinsic antibiotic resistance (IRAR) of multiple bacterial species by promoting the expression of a novel dual-function importer. In addition, population-dependent behavior induced by 13-methyltetradecanoic acid, a quorum sensing signal molecule designated LeDSF, was involved in the IRAR process. This study highlights the dynamic regulation of bacterial antibiotic resistance by small signaling molecules and provides direction for new therapeutic strategies using traditional antibiotics in combination with signaling molecules.

scholarly journals Autoinducer-2-Regulated Genes in Streptococcus mutans UA159 and Global Metabolic Effect of the luxS Mutation

2007 ◽  
Vol 190 (1) ◽  
pp. 401-415 ◽  
Author(s):  
Helena Sztajer ◽  
André Lemme ◽  
Ramiro Vilchez ◽  
Stefan Schulz ◽  
Robert Geffers ◽  
...  
Keyword(s):  
Gene Expression ◽  
Quorum Sensing ◽  
Streptococcus Mutans ◽  
Bacterial Species ◽  
Regulatory Protein ◽  
Acid Tolerance ◽  
Null Mutant ◽  
Gram Positive ◽  
Signal Molecule ◽  
Autoinducer 2

ABSTRACT Autoinducer 2 (AI-2) is the only species-nonspecific autoinducer known in bacteria and is produced by both gram-negative and gram-positive organisms. Consequently, it is proposed to function as a universal quorum-sensing signal for interaction between bacterial species. AI-2 is produced as the by-product of a metabolic transformation carried out by the LuxS enzyme. To separate the metabolic function of the LuxS enzyme from the signaling role of AI-2, we carried out a global transcriptome analysis of a luxS null mutant culture of Streptococcus mutans UA159, an important cariogenic bacterium and a crucial component of the dental plaque biofilm community, in comparison to a luxS null mutant culture supplemented with chemically pure 4,5-dihydroxy-2,3-pentanedione, the precursor of AI-2. The data revealed fundamental changes in gene expression affecting 585 genes (30% of the genome) which could not be restored by the signal molecule AI-2 and are therefore not caused by quorum sensing but by lack of the transformation carried out by the LuxS enzyme in the activated methyl cycle. All functional classes of enzymes were affected, including genes known to be important for biofilm formation, bacteriocin synthesis, competence, and acid tolerance. At the same time, 59 genes were identified whose transcription clearly responded to the addition of AI-2. Some of them were related to protein synthesis, stress, and cell division. Three membrane transport proteins were upregulated which are not related to any of the known AI-2 transporters. Three transcription factors were identified whose transcription was stimulated repeatedly by AI-2 addition during growth. Finally, a global regulatory protein, the δ subunit of the RNA polymerase (rpoE), was induced 147-fold by AI-2, representing the largest differential gene expression observed. The data show that many phenotypes related to the luxS mutation cannot be ascribed to quorum sensing and have identified for the first time regulatory proteins potentially mediating AI-2-based signaling in gram-positive bacteria.

scholarly journals Quorum Sensing Protects Pseudomonas aeruginosa against Cheating by Other Species in a Laboratory Coculture Model

2015 ◽  
Vol 197 (19) ◽  
pp. 3154-3159 ◽  
Author(s):  
Nicole E. Smalley ◽  
Dingding An ◽  
Matthew R. Parsek ◽  
Josephine R. Chandler ◽  
Ajai A. Dandekar
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Public Goods ◽  
Public Good ◽  
Hydrogen Cyanide ◽  
Cooperative Behavior ◽  
Bacterial Species ◽  
Cell Communication ◽  
Content Type ◽  
Burkholderia Multivorans

ABSTRACTMany species of bacteria use a cell-cell communication system called quorum sensing (QS) to coordinate group activities. QS systems frequently regulate the production of exoproducts. Some of these products, such as proteases, are “public goods” that are shared among the population and vulnerable to cheating by nonproducing members of the population. Because the QS system of the opportunistic pathogenPseudomonas aeruginosaregulates several public goods, it can serve as a model for studying cooperation. Bacteria also commonly regulate antimicrobial production through QS. In this study, we focused on the hypothesis that QS-regulated antimicrobials may be important forP. aeruginosato protect against cheating by another bacterial species,Burkholderia multivorans.We assessed laboratory cocultures ofP. aeruginosaandB. multivoransand investigated the importance of threeP. aeruginosaQS-regulated antimicrobials, hydrogen cyanide, rhamnolipids, and phenazines, for competition. We found thatP. aeruginosadominates cocultures withB. multivoransand that the three antimicrobials together promoteP. aeruginosacompetitiveness, with hydrogen cyanide contributing the greatest effect. We show that these QS-regulated antimicrobials are also critical forP. aeruginosato preventB. multivoransfrom cheating under nutrient conditions where both species require aP. aeruginosaquorum-regulated protease for growth. Together our results highlight the importance of antimicrobials in protecting cooperating populations from exploitation by other species that can act as cheaters.IMPORTANCECooperative behaviors are threatened by social cheating, wherein individuals do not produce but nonetheless benefit from shared public goods. Bacteria have been shown to use several genetic mechanisms to restrain the emergence of cheaters from within the population, but public goods might also be used by other bacterial species in the vicinity. We demonstrate that a public good produced byPseudomonas aeruginosacan be used by another species,Burkholderia multivorans, to obtain carbon and energy. We also show thatP. aeruginosaantimicrobials that are coregulated with the public good prevent invasion by the cheating species. Our results demonstrate that cross-species cheating can occur and that coregulation of public goods with antimicrobials may stabilize cooperative behavior in mixed microbial communities.

scholarly journals Ecology drives the evolution of diverse siderophore-production strategies in the opportunistic human pathogen Pseudomonas aeruginosa

2021 ◽  
Author(s):  
Alexandre R.T. Figueiredo ◽  
Andreas Wagner ◽  
Rolf Kümmerli
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Public Goods ◽  
Communication Systems ◽  
Social Evolution ◽  
Iron Starvation ◽  
Evolutionary Forces ◽  
Social Traits ◽  
Selection For ◽  
Opportunistic Human Pathogen

AbstractBacteria often cooperate by secreting molecules that can be shared as public goods between cells. Because the production of public goods is subject to cheating by mutants that exploit the good without contributing to it, there has been great interest in elucidating the evolutionary forces that maintain cooperation. However, little is known on how bacterial cooperation evolves under conditions where cheating is unlikely of importance. Here we use experimental evolution to follow changes in the production of a model public good, the iron-scavenging siderophore pyoverdine, of the bacterium Pseudomonas aeruginosa. After 1200 generations of evolution in nine different environments, we observed that cheaters only reached high frequency in liquid medium with low iron availability. Conversely, when adding iron to reduce the cost of producing pyoverdine, we observed selection for pyoverdine hyper-producers. Similarly, hyper-producers also spread in populations evolved in highly viscous media, where relatedness between interacting individuals is higher. Whole-genome sequencing of evolved clones revealed that hyper-production is associated with mutations/deletions in genes encoding quorum-sensing communication systems, while cheater clones had mutations in the iron-starvation sigma factor or in pyoverdine biosynthesis genes. Our findings demonstrate that bacterial social traits can evolve rapidly in divergent directions, with particularly strong selection for increased levels of cooperation occurring in environments where individual dispersal is reduced, as predicted by social evolution theory. Moreover, we establish a regulatory link between pyoverdine production and quorum-sensing, showing that increased cooperation at one trait (pyoverdine) can be associated with the loss (quorum-sensing) of another social trait.

scholarly journals Protist predation can favour cooperation within bacterial species

2013 ◽  
Vol 9 (5) ◽  
pp. 20130548 ◽  
Author(s):  
Ville-Petri Friman ◽  
Stephen P. Diggle ◽  
Angus Buckling
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Public Goods ◽  
Trophic Interactions ◽  
Bacterial Species ◽  
Cell Signalling ◽  
Opportunistic Pathogen ◽  
Wild Type ◽  
Floating Cell ◽  
Cell Aggregations

Here, we studied how protist predation affects cooperation in the opportunistic pathogen bacterium Pseudomonas aeruginosa , which uses quorum sensing (QS) cell-to-cell signalling to regulate the production of public goods. By competing wild-type bacteria with QS mutants (cheats), we show that a functioning QS system confers an elevated resistance to predation. Surprisingly, cheats were unable to exploit this resistance in the presence of cooperators, which suggests that resistance does not appear to result from activation of QS-regulated public goods. Instead, elevated resistance of wild-type bacteria was related to the ability to form more predation-resistant biofilms. This could be explained by the expression of QS-regulated resistance traits in densely populated biofilms and floating cell aggregations, or alternatively, by a pleiotropic cost of cheating where less resistant cheats are selectively removed from biofilms. These results show that trophic interactions among species can maintain cooperation within species, and have further implications for P. aeruginosa virulence in environmental reservoirs by potentially enriching the cooperative and highly infective strains with functional QS system.

Modulation of Gut Microbiota through Dietary Phytochemicals as a Novel Anti-infective Strategy

2020 ◽  
Vol 17 (4) ◽  
pp. 498-506 ◽  
Author(s):  
Pavan K. Mujawdiya ◽  
Suman Kapur
Keyword(s):  
Microbial Community ◽  
Quorum Sensing ◽  
Population Density ◽  
Gut Microbiota ◽  
Biofilm Formation ◽  
Chemical Interaction ◽  
Bacterial Species ◽  
Critical Role ◽  
Bacterial Cells ◽  
Gut Microbes

: Quorum Sensing (QS) is a phenomenon in which bacterial cells communicate with each other with the help of several low molecular weight compounds. QS is largely dependent on population density, and it triggers when the concentration of quorum sensing molecules accumulate in the environment and crosses a particular threshold. Once a certain population density is achieved and the concentration of molecules crosses a threshold, the bacterial cells show a collective behavior in response to various chemical stimuli referred to as “auto-inducers”. The QS signaling is crucial for several phenotypic characteristics responsible for bacterial survival such as motility, virulence, and biofilm formation. Biofilm formation is also responsible for making bacterial cells resistant to antibiotics. : The human gut is home to trillions of bacterial cells collectively called “gut microbiota” or “gut microbes”. Gut microbes are a consortium of more than 15,000 bacterial species and play a very crucial role in several body functions such as metabolism, development and maturation of the immune system, and the synthesis of several essential vitamins. Due to its critical role in shaping human survival and its modulating impact on body metabolisms, the gut microbial community has been referred to as “the forgotten organ” by O`Hara et al. (2006) [1]. Several studies have demonstrated that chemical interaction between the members of bacterial cells in the gut is responsible for shaping the overall microbial community. : Recent advances in phytochemical research have generated a lot of interest in finding new, effective, and safer alternatives to modern chemical-based medicines. In the context of antimicrobial research various plant extracts have been identified with Quorum Sensing Inhibitory (QSI) activities among bacterial cells. This review focuses on the mechanism of quorum sensing and quorum sensing inhibitors isolated from natural sources.

scholarly journals Effect of Titanium Dioxide Nanoparticles on the Expression of Efflux Pump and Quorum-Sensing Genes in MDR Pseudomonas aeruginosa Isolates

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 625
Author(s):  
Fatma Y. Ahmed ◽  
Usama Farghaly Aly ◽  
Rehab Mahmoud Abd El-Baky ◽  
Nancy G. F. M. Waly
Keyword(s):  
Titanium Dioxide ◽  
Quorum Sensing ◽  
Biofilm Formation ◽  
Antimicrobial Agents ◽  
Efflux Pump ◽  
Titanium Dioxide Nanoparticles ◽  
Sol Gel ◽  
Efflux Pumps ◽  
Antibiofilm Activity ◽  
The Impact

Most of the infections caused by multi-drug resistant (MDR) P. aeruginosa strains are extremely difficult to be treated with conventional antibiotics. Biofilm formation and efflux pumps are recognized as the major antibiotic resistance mechanisms in MDR P. aeruginosa. Biofilm formation by P. aeruginosa depends mainly on the cell-to-cell communication quorum-sensing (QS) systems. Titanium dioxide nanoparticles (TDN) have been used as antimicrobial agents against several microorganisms but have not been reported as an anti-QS agent. This study aims to evaluate the impact of titanium dioxide nanoparticles (TDN) on QS and efflux pump genes expression in MDR P. aeruginosa isolates. The antimicrobial susceptibility of 25 P. aeruginosa isolates were performed by Kirby–Bauer disc diffusion. Titanium dioxide nanoparticles (TDN) were prepared by the sol gel method and characterized by different techniques (DLS, HR-TEM, XRD, and FTIR). The expression of efflux pumps in the MDR isolates was detected by the determination of MICs of different antibiotics in the presence and absence of carbonyl cyanide m-chlorophenylhydrazone (CCCP). Biofilm formation and the antibiofilm activity of TDN were determined using the tissue culture plate method. The effects of TDN on the expression of QS genes and efflux pump genes were tested using real-time polymerase chain reaction (RT-PCR). The average size of the TDNs was 64.77 nm. It was found that TDN showed a significant reduction in biofilm formation (96%) and represented superior antibacterial activity against P. aeruginosa strains in comparison to titanium dioxide powder. In addition, the use of TDN alone or in combination with antibiotics resulted in significant downregulation of the efflux pump genes (MexY, MexB, MexA) and QS-regulated genes (lasR, lasI, rhll, rhlR, pqsA, pqsR) in comparison to the untreated isolate. TDN can increase the therapeutic efficacy of traditional antibiotics by affecting efflux pump expression and quorum-sensing genes controlling biofilm production.

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