Quorum sensing enhancement of the stress response promotes resistance to quorum quenching and prevents social cheating

García‐Contreras, Rodolfo; Nuñez-López, Leslie; Jasso‐Chávez, Ricardo; Kwan, Brian W.; Belmont, Javier; Rangel-Vega, Adrián; Maeda, Takeyasu; Wood, Thomas K.

doi:10.1038/ismej.2014.98

Cited by 177 publications

(116 citation statements)

References 46 publications

Supporting

Mentioning

106

Contrasting

Order By: Relevance

“…Similar to the idea that the link between QS and private goods prevents cheating, recently, we demonstrated (García-Contreras et al, 2015) that the higher sensitivity of QS-deficient mutants to stress restricts the generation and spread of social cheaters (lasR mutants) in P. aeruginosa (Figure 1d). …”

Section: Possible Impact Of Environmental and Host Conditions On The supporting

confidence: 74%

“…These mutants are also found in clinical isolates from infections, indicating these processes could also exist under the relevant in vivo growth (Diggle et al, 2007;Sandoz et al, 2007). In addition, although the percentage of cheaters and cooperators in experiments often reach an equilibrium in which both kinds of cells coexist (Dandekar et al, 2013;García-Contreras et al, 2015;Sandoz et al, 2007), an overload of cheaters can collapse the population by overexploitation of the cooperators. This collapse in ecology is known as the tragedy of the commons.…”

mentioning

confidence: 97%

See 1 more Smart Citation

Can resistance against quorum-sensing interference be selected?

2015

Self Cite

View full text Add to dashboard Cite

Quorum-sensing (QS) interference is a novel therapy to fight bacterial infections that, unlike conventional antibiotic treatments, is focused on reducing the damage caused by pathogens (virulence) rather than focused on inhibiting their growth. Given this ideal, it was predicted that this approach will be impervious to or at least much less prone to resistance in bacterial populations. However, recently, resistance mechanisms against well-characterized quorum quenchers (QQs) have been found in the laboratory as well as in clinical strains, demonstrating that the rise of resistance against these kinds of compounds is possible. Nevertheless, it has been argued that even if resistance mechanisms against QS interference exist, this fact does not guarantee that resistance will spread. In the present work, we discuss recent insights derived from the latest experiments to address this question. In addition, we explain how environmental conditions like the stress produced by the host immune system may influence the selection of resistance and eventually lead to the selection of QS interference-resistant bacteria in a clinical setting.

show abstract

Section: Possible Impact Of Environmental and Host Conditions On The supporting

confidence: 74%

mentioning

confidence: 97%

Can resistance against quorum-sensing interference be selected?

2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…In the wild type, QS is known to elicit increased expression of enzymes involved in ROS detoxification, such as superoxide dismutases (Mn-SOD and Fe-SOD), the major catalase KatA (69), and NADPH-generating glucose-6-phosphate dehydrogenase (NADPH is required for the synthesis of glutathione). Indeed, it has been suggested recently that since they are "private goods," the expression of these detoxification enzymes is another key factor suppressing the appearance of "social cheats" in the population (70). Since these enzymes would no longer be upregulated in the lasI rhlI mutant, we speculate that the elevated levels of polyamines reflect an alternative metabolic response to increased ROS-induced stress as the culture enters stationary phase.…”

Section: Discussionmentioning

confidence: 79%

Quorum Sensing Is Accompanied by Global Metabolic Changes in the Opportunistic Human Pathogen Pseudomonas aeruginosa

2015

View full text Add to dashboard Cite

Pseudomonas aeruginosa uses N-acyl-homoserine lactone (AHL)-dependent quorum sensing (QS) systems to control the expression of secreted effectors. These effectors can be crucial to the ecological fitness of the bacterium, playing roles in nutrient acquisition, microbial competition, and virulence. In this study, we investigated the metabolic consequences of AHL-dependent QS by monitoring the metabolic profile(s) of a lasI rhlI double mutant (unable to make QS signaling molecules) and its wild-type progenitor as they progressed through the growth curve. Analysis of culture supernatants by 1 H-nuclear magnetic resonance ( 1 H-NMR) spectroscopy revealed that at the point where AHL concentrations peaked in the wild type, the metabolic footprints (i.e., extracellular metabolites) of the wild-type and lasI rhlI mutant diverged. Subsequent gas chromatography-mass spectrometry (GC-MS)-based analysis of the intracellular metabolome revealed QS-dependent perturbations in around one-third of all identified metabolites, including altered concentrations of tricarboxylic acid (TCA) cycle intermediates, amino acids, and fatty acids. Further targeted fatty acid methyl ester (FAME) GC-MS-based profiling of the cellular total fatty acid pools revealed that QS leads to changes associated with decreased membrane fluidity and higher chemical stability. However, not all of the changes we observed were necessarily a direct consequence of QS; liquid chromatography (LC)-MS analyses revealed that polyamine levels were elevated in the lasI rhlI mutant, perhaps a response to the absence of QS-dependent adaptations. Our data suggest that QS leads to a global readjustment in central metabolism and provide new insight into the metabolic changes associated with QS during stationary-phase adaptation. IMPORTANCEQuorum sensing (QS) is a transcriptional regulatory mechanism that allows bacteria to coordinate their gene expression profile with the population cell density. The opportunistic human pathogen Pseudomonas aeruginosa uses QS to control the production of secreted virulence factors. In this study, we show that QS elicits a global "metabolic rewiring" in P. aeruginosa. This metabolic rerouting of fluxes is consistent with a variety of drivers, ranging from altered QS-dependent transcription of "metabolic genes" through to the effect(s) of global "metabolic readjustment" as a consequence of QS-dependent exoproduct synthesis, as well as a general stress response, among others. To our knowledge, this is the first study of its kind to assess the global impact of QS on the metabolome. T he gammaproteobacterium Pseudomonas aeruginosa is widely distributed in the environment (1, 2). The organism is a human pathogen and is responsible for a range of acute infections, urinary tract infections, and respiratory infections (3). In addition, it is also associated with certain chronic infections, such as those that often develop in the airways of cystic fibrosis patients (4, 5). Such exquisite adaptability to different niches requires a complex re...

show abstract

“…Quorum sensing enhances the bacterial oxidative stress response (14). High concentrations of cinnamon oil inhibited the oxidative stress response through elimination of the mRNA levels of genes encoding the oxidative stress response regulons as well as RpoS protein production.…”

Section: Discussionmentioning

confidence: 99%

“…Prophage induction can be caused by factors provoking SOS response, which activates the RecA protein, resulting in self-cleavage of the phageencoded cI repressor, initiation of phage transcription, and further the transcription of stx genes (13). Quorum sensing (QS) is a global virulence regulator of E. coli O157:H7 as well as a positive regulator of bacterial oxidative stress response (14), which activates the SOS stress response through both LuxS/autoinducer 2 (AI-2) signaling and QseBC signaling (15,16). OxyR-mediated oxidative stress inhibits prophage induction in -phage-infected E. coli MG1655 (17).…”

Section: Importancementioning

confidence: 99%

Cinnamon Oil Inhibits Shiga Toxin Type 2 Phage Induction and Shiga Toxin Type 2 Production in Escherichia coli O157:H7

Sheng

Rasco

Zhu

2016

Appl Environ Microbiol

View full text Add to dashboard Cite

This study evaluated the inhibitory effect of cinnamon oil against Escherichia coli O157:H7 Shiga toxin (Stx) production and further explored the underlying mechanisms. The MIC and minimum bactericidal concentration (MBC) of cinnamon oil against E. coli O157:H7 were 0.025% and 0.05% (vol/vol), respectively. Cinnamon oil significantly reduced Stx2 production and the stx 2 mRNA expression that is associated with diminished Vero cell cytotoxicity. Consistently, induction of the Stx-converting phage where the stx 2 gene is located, along with the total number of phages, decreased proportionally to cinnamon oil concentration. In line with decreased Stx2 phage induction, cinnamon oil at 0.75؋ and 1.0؋ MIC eliminated RecA, a key mediator of SOS response, polynucleotide phosphorylase (PNPase), and poly(A) polymerase (PAP I), which positively regulate Stx-converting phages, contributing to reduced Stx-converting phage induction and Stx production. Furthermore, cinnamon oil at 0.75؋ and 1.0؋ MIC strongly inhibited the qseBC and luxS expression associated with decreased AI-2 production, a universal quorum sensing signaling molecule. However, the expression of oxidative stress response genes oxyR, soxR, and rpoS was increased in response to cinnamon oil at 0.25؋ or 0.5؋ MIC, which may contribute to stunted bacterial growth and reduced Stx2 phage induction and Stx2 production due to the inhibitory effect of OxyR on prophage activation. Collectively, cinnamon oil inhibits Stx2 production and Stx2 phage induction in E. coli O157:H7 in multiple ways. IMPORTANCEThis study reports the inhibitory effect of cinnamon oil on Shiga toxin 2 phage induction and Shiga toxin 2 production. Subinhibitory concentrations (concentrations below the MIC) of cinnamon oil reduced Stx2 production, stx 2 mRNA expression, and cytotoxicity on Vero cells. Subinhibitory concentrations of cinnamon oil also dramatically reduced both the Stx2 phage and total phage induction in E. coli O157:H7, which may be due to the suppression of RNA polyadenylation enzyme PNPase at 0.25؋ to 1.0؋ MIC and the downregulation of bacterial SOS response key regulator RecA and RNA polyadenylation enzyme PAP I at 0.75؋ or 1.0؋ MIC. Cinnamon oil at higher levels (0.75؋ and 1.0؋ MIC) eliminated quorum sensing and oxidative stress. Therefore, cinnamon oil has potential applications as a therapeutic to control E. coli O157:H7 infection through inhibition of bacterial growth and virulence factors. E scherichia coli O157:H7 is an important foodborne pathogen that is associated with hemorrhagic colitis, hemolytic-uremic syndrome (HUS), and death (1). More than 63,000 cases of foodborne illness are estimated to be caused by E. coli O157:H7 annually in the United States (2). Outbreaks have been associated with ground beef, ready-to-eat salad, cheese, apple juice, and other foods (3-6).Shiga toxin (Stx) is a major virulence factor of E. coli O157:H7. Its production in the gastrointestinal tract in conjunction with other virulence factors induces hemorrhagic colitis, and its entry...

show abstract

Quorum sensing enhancement of the stress response promotes resistance to quorum quenching and prevents social cheating

Cited by 177 publications

References 46 publications

Can resistance against quorum-sensing interference be selected?

Can resistance against quorum-sensing interference be selected?

Quorum Sensing Is Accompanied by Global Metabolic Changes in the Opportunistic Human Pathogen Pseudomonas aeruginosa

Cinnamon Oil Inhibits Shiga Toxin Type 2 Phage Induction and Shiga Toxin Type 2 Production in Escherichia coli O157:H7

Contact Info

Product

Resources

About