Pseudomonas aeruginosa LasR overexpression leads to a RsaL-independent pyocyanin production inhibition in a low phosphate condition

Soto-Aceves, Martín Paolo; González‐Valdez, Abigail; Cocotl‐Yañez, Miguel; Soberón-Chávez, Gloria

doi:10.1099/mic.0.001262

Cited by 4 publications

(4 citation statements)

References 42 publications

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“…To determine the impact of LasR sensitivity on gene regulation, we measured the transcriptional activity from the promoters of four quorum-regulated genes: (i) rsaL, which is activated by LasR; (ii) lasB, which is activated by both LasR and RhlR; (iii) rhlA , a gene required for rhamnolipid biosynthesis, which is activated by RhlR; and (iv) phzA1 , a gene required for the production of pyocyanin and related phenazines, which is positively regulated by RhlR but is both directly and indirectly negatively regulated by LasR ( Fig. 1A ) ( 15 , 18 , 19 ). Because LasR positively regulates the Rhl system, altered LasR sensitivity may impact RhlR activity, but RhlR activity is also dependent upon several other factors ( 20 – 23 ).…”

Section: Resultsmentioning

confidence: 99%

A balancing act: investigations on the impact of altered signal sensitivity in bacterial quorum sensing

Miranda,

Greenberg

2023

J Bacteriol

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Many bacterial species communicate and cooperate with kin using a form of cell-cell signaling called quorum sensing. Sensitivity and selectivity are fundamental properties of quorum sensing, and of cell signaling more generally, as they dictate the ability of cells to accurately detect and interpret signals. In this study, we investigate the impact of signal sensitivity on gene regulation and on bacterial fitness using two variants of the LasR quorum sensing receptor in the opportunistic pathogen Pseudomonas aeruginosa . Our studies reinforce that altering LasR signal-binding residues tends to result in decreased signal selectivity. We also find that LasR hyper-sensitivity results in earlier and stronger expression of LasR-regulated genes, whereas hypo-sensitivity results in delayed transcription from both LasR- and RhlR-regulated promoters. Furthermore, strains expressing either the hyper- or hypo-sensitive LasR polypeptide exhibit reduced production of pyocyanin, a key antimicrobial that impacts intra- and interspecies competition as well as pathogenicity. These changes to gene expression underscore the complex regulatory network by which P. aeruginosa controls group behaviors. Ultimately, altered signal sensitivity results in a fitness defect for LasR hyper-sensitive cells during kin competition against wild-type P. aeruginosa and for hypo-sensitive cells during interspecies competition against the opportunistic pathogen Burkholderia multivorans . Our findings highlight the delicate balance between group behaviors regulated by quorum sensing and bacterial fitness and contribute to a better understanding of the evolutionary pressures that may tune sensitivity in cell-cell signaling. IMPORTANCE Quorum sensing (QS) is a widespread form of cell-cell signaling that regulates group behaviors important for competition and cooperation within bacterial communities. The QS systems from different bacterial species have diverse properties, but the functional consequences of this diversity are largely unknown. Taking advantage of hyper- and hypo-sensitive QS receptor variants in the opportunistic pathogen Pseudomonas aeruginosa , we examine the costs and benefits of altered signal sensitivity. We find that the sensitivity of a model QS receptor, LasR, impacts the timing and level of quorum gene expression, and fitness during intra- and interspecies competition. These findings suggest competition with kin and with other bacterial species work together to tune signal sensitivity.

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Section: Resultsmentioning

confidence: 99%

A balancing act: investigations on the impact of altered signal sensitivity in bacterial quorum sensing

Miranda,

Greenberg

2023

J Bacteriol

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“…The enzymes necessary for PYO synthesis are encoded by two duplicated operons ( phzA1‐G1 and phzA2‐G2 ) and genes phzS , and phzM (Mavrodi et al., 2001). The phzA1 promoter contains a las box that RhlR recognizes for its transcriptional activation (Groleau et al., 2020; Higgins et al., 2018; Whiteley & Greenberg, 2001) and is negatively regulated by LasR (Soto‐Aceves et al., 2022). The promoter of phzA2 does not contain a las box, but its transcription also depends on RhlR (Higgins et al., 2018).…”

Section: Introductionmentioning

confidence: 99%

The alternative sigma factor RpoS regulates Pseudomonas aeruginosa quorum sensing response by repressing the pqsABCDE operon and activating vfr

Muriel‐Millán,

Montelongo‐Martínez,

González‐Valdez

et al. 2024

Molecular Microbiology

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Pseudomonas aeruginosa is an important opportunistic pathogen. Several of its virulence‐related processes, including the synthesis of pyocyanin (PYO) and biofilm formation, are controlled by quorum sensing (QS). It has been shown that the alternative sigma factor RpoS regulates QS through the reduction of lasR and rhlR transcription (encoding QS regulators). However, paradoxically, the absence of RpoS increases PYO production and biofilm development (that are RhlR dependent) by unknown mechanisms. Here, we show that RpoS represses pqsE transcription, which impacts the stability and activity of RhlR. In the absence of RpoS, rhlR transcript levels are reduced but not the RhlR protein concentration, presumably by its stabilization by PqsE, whose expression is increased. We also report that PYO synthesis and the expression of pqsE and phzA1B1C1D1E1F1G1 operon exhibit the same pattern at different RpoS concentrations, suggesting that the RpoS‐dependent PYO production is due to its ability to modify PqsE concentration, which in turn modulates the activation of the phzA1 promoter by RhlR. Finally, we demonstrate that RpoS favors the expression of Vfr, which activates the transcription of lasR and rhlR. Our study contributes to the understanding of how RpoS modulates the QS response in P. aeruginosa, exerting both negative and positive regulation.

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“…The Las system is often placed on top of this hierarchy due to positive regulation of the Rhl and PQS system ( 10 ). However, this hierarchy is flexible and can shift under certain growth conditions ( 12 ). Some papers report 2-(2-hydroxylphenyl)-thiazole-4-carbaldehyde (IQS) as a fourth QS system in P. aeruginosa .…”

Section: Introductionmentioning

confidence: 99%

Paecilomycone Inhibits Quorum Sensing in Gram-Negative Bacteria

et al. 2023

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Antibiotics are becoming less effective against bacterial infections due to the evolution of resistance among bacteria. Pseudomonas aeruginosa is a Gram-negative pathogen that causes major health care concerns and is difficult to treat due to its high intrinsic resistance to antimicrobial agents. Therefore, new targets are needed, and an interesting approach is to target quorum sensing (QS).

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Pseudomonas aeruginosa LasR overexpression leads to a RsaL-independent pyocyanin production inhibition in a low phosphate condition

Cited by 4 publications

References 42 publications

A balancing act: investigations on the impact of altered signal sensitivity in bacterial quorum sensing

A balancing act: investigations on the impact of altered signal sensitivity in bacterial quorum sensing

The alternative sigma factor RpoS regulates Pseudomonas aeruginosa quorum sensing response by repressing the pqsABCDE operon and activating vfr

Paecilomycone Inhibits Quorum Sensing in Gram-Negative Bacteria

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