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Homeostatic interplay between bacterial cell-cell signaling and iron in virulence.

Hazan R, He J, Xiao G, Dekimpe V, Apidianakis Y, Lesic B, Astrakas C, Déziel E, Lépine F, Rahme LG - PLoS Pathog. (2010)

Bottom Line: Our results show that P. aeruginosa modulates the intensity of its virulence response, at least in part, through this multi-layered interplay.Our findings underscore the importance of the homeostatic interplay that balances competition within and between QS systems via cell-cell signaling molecules and environmental cues in the control of virulence gene expression.Elucidation of the fine-tuning of this complex relationship offers novel insights into the regulation of these systems and may inform strategies designed to limit infections caused by P. aeruginosa and related human pathogens.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts, United States of America.

ABSTRACT
Pathogenic bacteria use interconnected multi-layered regulatory networks, such as quorum sensing (QS) networks to sense and respond to environmental cues and external and internal bacterial cell signals, and thereby adapt to and exploit target hosts. Despite the many advances that have been made in understanding QS regulation, little is known regarding how these inputs are integrated and processed in the context of multi-layered QS regulatory networks. Here we report the examination of the Pseudomonas aeruginosa QS 4-hydroxy-2-alkylquinolines (HAQs) MvfR regulatory network and determination of its interaction with the QS acyl-homoserine-lactone (AHL) RhlR network. The aim of this work was to elucidate paradigmatically the complex relationships between multi-layered regulatory QS circuitries, their signaling molecules, and the environmental cues to which they respond. Our findings revealed positive and negative homeostatic regulatory loops that fine-tune the MvfR regulon via a multi-layered dependent homeostatic regulation of the cell-cell signaling molecules PQS and HHQ, and interplay between these molecules and iron. We discovered that the MvfR regulon component PqsE is a key mediator in orchestrating this homeostatic regulation, and in establishing a connection to the QS rhlR system in cooperation with RhlR. Our results show that P. aeruginosa modulates the intensity of its virulence response, at least in part, through this multi-layered interplay. Our findings underscore the importance of the homeostatic interplay that balances competition within and between QS systems via cell-cell signaling molecules and environmental cues in the control of virulence gene expression. Elucidation of the fine-tuning of this complex relationship offers novel insights into the regulation of these systems and may inform strategies designed to limit infections caused by P. aeruginosa and related human pathogens.

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Homeostatic interplay between PQS and iron: Iron fine-tunes PQS activities.The effect of iron on MvfR induction was tested using the pqsA-GFP reporter in PA14 (A) and PA14 pqsA−::pqsH cells treated with PQS (1 mg/L) (B). The effect of iron on pyocyanin production was tested when PQS was supplied at 1 mg/L or 20 mg/L (C). The cells were grown in low iron medium D-TSB or in media supplemented with iron (FeCl3 or FeSO4, 200 µM). Asterisks show samples that are statistically significant different (P value<0.05) from the PQS 1 mg/L treated sample.
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ppat-1000810-g005: Homeostatic interplay between PQS and iron: Iron fine-tunes PQS activities.The effect of iron on MvfR induction was tested using the pqsA-GFP reporter in PA14 (A) and PA14 pqsA−::pqsH cells treated with PQS (1 mg/L) (B). The effect of iron on pyocyanin production was tested when PQS was supplied at 1 mg/L or 20 mg/L (C). The cells were grown in low iron medium D-TSB or in media supplemented with iron (FeCl3 or FeSO4, 200 µM). Asterisks show samples that are statistically significant different (P value<0.05) from the PQS 1 mg/L treated sample.

Mentions: To examine how iron starvation is translated in the context of MvfR signaling, we first examined whether there is a relationship between iron starvation and the regulation of PQS and MvfR regulon genes. We compared pqsA transcription using a pqsA-GFP (ASV) reporter in PA14 cells grown in the absence (D-TSB medium) or presence of high iron levels. Figure 5A demonstrates that iron significantly reduced pqsA transcription. Subsequently, we examined the effect of iron directly on the induction of pqs operon transcription in presence only of PQS and not of other HAQs in pqsA−::pqsH− mutant cells. Using 1 mg/L PQS, an amount sufficient to fully induce pqs operon transcription and increasing concentrations of FeCl3 Figure 5B shows an iron concentration-dependent effect on pqsA gene expression.


Homeostatic interplay between bacterial cell-cell signaling and iron in virulence.

Hazan R, He J, Xiao G, Dekimpe V, Apidianakis Y, Lesic B, Astrakas C, Déziel E, Lépine F, Rahme LG - PLoS Pathog. (2010)

Homeostatic interplay between PQS and iron: Iron fine-tunes PQS activities.The effect of iron on MvfR induction was tested using the pqsA-GFP reporter in PA14 (A) and PA14 pqsA−::pqsH cells treated with PQS (1 mg/L) (B). The effect of iron on pyocyanin production was tested when PQS was supplied at 1 mg/L or 20 mg/L (C). The cells were grown in low iron medium D-TSB or in media supplemented with iron (FeCl3 or FeSO4, 200 µM). Asterisks show samples that are statistically significant different (P value<0.05) from the PQS 1 mg/L treated sample.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2837411&req=5

ppat-1000810-g005: Homeostatic interplay between PQS and iron: Iron fine-tunes PQS activities.The effect of iron on MvfR induction was tested using the pqsA-GFP reporter in PA14 (A) and PA14 pqsA−::pqsH cells treated with PQS (1 mg/L) (B). The effect of iron on pyocyanin production was tested when PQS was supplied at 1 mg/L or 20 mg/L (C). The cells were grown in low iron medium D-TSB or in media supplemented with iron (FeCl3 or FeSO4, 200 µM). Asterisks show samples that are statistically significant different (P value<0.05) from the PQS 1 mg/L treated sample.
Mentions: To examine how iron starvation is translated in the context of MvfR signaling, we first examined whether there is a relationship between iron starvation and the regulation of PQS and MvfR regulon genes. We compared pqsA transcription using a pqsA-GFP (ASV) reporter in PA14 cells grown in the absence (D-TSB medium) or presence of high iron levels. Figure 5A demonstrates that iron significantly reduced pqsA transcription. Subsequently, we examined the effect of iron directly on the induction of pqs operon transcription in presence only of PQS and not of other HAQs in pqsA−::pqsH− mutant cells. Using 1 mg/L PQS, an amount sufficient to fully induce pqs operon transcription and increasing concentrations of FeCl3 Figure 5B shows an iron concentration-dependent effect on pqsA gene expression.

Bottom Line: Our results show that P. aeruginosa modulates the intensity of its virulence response, at least in part, through this multi-layered interplay.Our findings underscore the importance of the homeostatic interplay that balances competition within and between QS systems via cell-cell signaling molecules and environmental cues in the control of virulence gene expression.Elucidation of the fine-tuning of this complex relationship offers novel insights into the regulation of these systems and may inform strategies designed to limit infections caused by P. aeruginosa and related human pathogens.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts, United States of America.

ABSTRACT
Pathogenic bacteria use interconnected multi-layered regulatory networks, such as quorum sensing (QS) networks to sense and respond to environmental cues and external and internal bacterial cell signals, and thereby adapt to and exploit target hosts. Despite the many advances that have been made in understanding QS regulation, little is known regarding how these inputs are integrated and processed in the context of multi-layered QS regulatory networks. Here we report the examination of the Pseudomonas aeruginosa QS 4-hydroxy-2-alkylquinolines (HAQs) MvfR regulatory network and determination of its interaction with the QS acyl-homoserine-lactone (AHL) RhlR network. The aim of this work was to elucidate paradigmatically the complex relationships between multi-layered regulatory QS circuitries, their signaling molecules, and the environmental cues to which they respond. Our findings revealed positive and negative homeostatic regulatory loops that fine-tune the MvfR regulon via a multi-layered dependent homeostatic regulation of the cell-cell signaling molecules PQS and HHQ, and interplay between these molecules and iron. We discovered that the MvfR regulon component PqsE is a key mediator in orchestrating this homeostatic regulation, and in establishing a connection to the QS rhlR system in cooperation with RhlR. Our results show that P. aeruginosa modulates the intensity of its virulence response, at least in part, through this multi-layered interplay. Our findings underscore the importance of the homeostatic interplay that balances competition within and between QS systems via cell-cell signaling molecules and environmental cues in the control of virulence gene expression. Elucidation of the fine-tuning of this complex relationship offers novel insights into the regulation of these systems and may inform strategies designed to limit infections caused by P. aeruginosa and related human pathogens.

Show MeSH
Related in: MedlinePlus