A new Pseudomonas quinolone signal (PQS) binding partner: MexG

Hodgkinson, James T.; Gross, Jeremy; Baker, Ysobel R; Spring, David R.; Welch, Martin

doi:10.1039/c5sc04197j

Cited by 43 publications

(35 citation statements)

References 46 publications

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“…We calculated a K D of pyocyanin to MexG to be about 0.6 μM (Figure 5C). This suggests that the binding is quite strong, with the K D is similar to what was previously reported for MexG and PQS 23 .…”

Section: Resultssupporting

confidence: 88%

Kinetic Control of Quorum Sensing in Pseudomonas aeruginosa by Multidrug Efflux Pumps

et al. 2017

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Pseudomonas aeruginosa is an important human pathogen, the physiology and virulence of which are under the control of quorum sensing signals. These signals often have dual roles, functioning as toxins to some cells and as oxidative-stress protectors for their producer cells. Hence, their internal and external concentrations should be tightly controlled. In this study, we analyzed the interplay between the multidrug efflux transporters MexEF-OprN and MexG/HI-OpmD in quorum sensing of P. aeruginosa. We found that the two transporters have overlapping substrate specificities but different efficiencies. When overproduced, both MexEF-OprN and MexG/HI-OpmD provide clinical levels of resistance to diverse fluoroquinolones and protect P. aeruginosa against toxic phenazines. However, this similarity is enabled by synergistic interactions with the outer membrane. In hyperporinated cells, MexG/HI-OpmD is saturated by much lower concentrations of fluoroquinolones but is more efficient than MexEF-OprN in efflux of phenazines. Unlike MexEF-OprN, mutational inactivation of MexG/HI-OpmD reduces the levels of pyocyanin and makes P. aeruginosa cells hypersusceptible to phenazines. Our results further show that MexG binds pyocyanin, physically associates with MexHI and represses the activity of the transporter, revealing a negative regulatory role of this protein. We conclude that differences in kinetic properties of transporters are critical to maintain proper intra- and extra- cellular concentrations of phenazines and other signaling molecules, and that MexG/HI-OpmD controls the steady-state in the synthesis and secretion of phenazines.

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Section: Resultssupporting

confidence: 88%

Kinetic Control of Quorum Sensing in Pseudomonas aeruginosa by Multidrug Efflux Pumps

et al. 2017

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“…To support this hypothesis, PQS is associated with the MexGHI-OpmD efflux pump, which controls antibiotic susceptibility through the production of PQS and N-acyl-L-homoserine lactone QS signal molecules and is also regulated by VqsR (44,67). A recent study demonstrates that MexG is capable of binding PQS (68). The studies by Wu et al demonstrated that the pro-oxidant paraquat promoted antibiotic tolerance, underscoring the importance of oxidative stress in antibiotic tolerance (69).…”

Section: Discussionmentioning

confidence: 99%

RpoN Modulates Carbapenem Tolerance in Pseudomonas aeruginosa through Pseudomonas Quinolone Signal and PqsE

Viducic

Murakami

Amoh

et al. 2016

Antimicrob Agents Chemother

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bThe ability of Pseudomonas aeruginosa to rapidly modulate its response to antibiotic stress and persist in the presence of antibiotics is closely associated with the process of cell-to-cell signaling. The alternative sigma factor RpoN ( 54 ) is involved in the regulation of quorum sensing (QS) and plays an important role in the survival of stationary-phase cells in the presence of carbapenems. Here, we demonstrate that a ⌬rpoN mutant grown in nutrient-rich medium has increased expression of pqsA, pqsH, and pqsR throughout growth, resulting in the increased production of the Pseudomonas quinolone signal (PQS). The link between pqsA and its role in carbapenem tolerance was studied using a ⌬rpoN ⌬pqsA mutant, in which the carbapenem-tolerant phenotype of the ⌬rpoN mutant was abolished. In addition, we demonstrate that another mechanism leading to carbapenem tolerance in the ⌬rpoN mutant is mediated through pqsE. Exogenously supplied PQS abolished the biapenem-sensitive phenotype of the ⌬rpoN ⌬pqsA mutant, and overexpression of pqsE failed to alter the susceptibility of the ⌬rpoN ⌬pqsA mutant to biapenem. The mutations in the ⌬rpoN ⌬rhlR mutant and the ⌬rpoN ⌬pqsH mutant led to susceptibility to biapenem. Comparison of the changes in the expression of the genes involved in QS in wild-type PAO1 with their expression in the ⌬rpoN mutant and the ⌬rpoN mutant-derived strains demonstrated the regulatory effect of RpoN on the transcript levels of rhlR, vqsR, and rpoS. The findings of this study demonstrate that RpoN negatively regulates the expression of PQS in nutrient-rich medium and provide evidence that RpoN interacts with pqsA, pqsE, pqsH, and rhlR in response to antibiotic stress.

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“…PQS and HQNO contain primary alkyl groups that could be coupled to an Affi-gel 10 (Bio-Rad, Hercules, CA, USA) matrix68. The compound–matrix coupling was performed by incubation of 1.5 ml Affi-gel media with 0.3 mg of each compound and incubated at 4 °C for 2 h following the Bio-Rad's manual.…”

Section: Methodsmentioning

confidence: 99%

A Pseudomonas T6SS effector recruits PQS-containing outer membrane vesicles for iron acquisition

et al. 2017

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Iron sequestration by host proteins contributes to the defence against bacterial pathogens, which need iron for their metabolism and virulence. A Pseudomonas aeruginosa mutant lacking all three known iron acquisition systems retains the ability to grow in media containing iron chelators, suggesting the presence of additional pathways involved in iron uptake. Here we screen P. aeruginosa mutants defective in growth in iron-depleted media and find that gene PA2374, proximal to the type VI secretion system H3 (H3-T6SS), functions synergistically with known iron acquisition systems. PA2374 (which we have renamed TseF) appears to be secreted by H3-T6SS and is incorporated into outer membrane vesicles (OMVs) by directly interacting with the iron-binding Pseudomonas quinolone signal (PQS), a cell–cell signalling compound. TseF facilitates the delivery of OMV-associated iron to bacterial cells by engaging the Fe(III)-pyochelin receptor FptA and the porin OprF. Our results reveal links between type VI secretion, cell–cell signalling and classic siderophore receptors for iron acquisition in P. aeruginosa.

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A new Pseudomonas quinolone signal (PQS) binding partner: MexG

Abstract: Pseudomonas Quinolone Signal (PQS) probes capture a new binding partner for this signal molecule.

Cited by 43 publications

References 46 publications

Kinetic Control of Quorum Sensing in Pseudomonas aeruginosa by Multidrug Efflux Pumps

Kinetic Control of Quorum Sensing in Pseudomonas aeruginosa by Multidrug Efflux Pumps

RpoN Modulates Carbapenem Tolerance in Pseudomonas aeruginosa through Pseudomonas Quinolone Signal and PqsE

A Pseudomonas T6SS effector recruits PQS-containing outer membrane vesicles for iron acquisition

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