A broad range quorum sensing inhibitor working through sRNA inhibition

Tim H. Jakobsen; Anders N. Warming; Rebecca M. Vejborg; Joana A. Moscoso; Marc Stegger; Frederik Lorenzen; Morten Rybtke; Jens B. Andersen; Rico Petersen; Paal Skytt Andersen; Thomas E. Nielsen; Tim Tolker-Nielsen; Alain Filloux; Hanne Ingmer; Michael Givskov

doi:10.1038/s41598-017-09886-8

A broad range quorum sensing inhibitor working through sRNA inhibition

Tim H. Jakobsen^*, Anders N. Warming, Rebecca M. Vejborg, Joana A. Moscoso, Marc Stegger, Frederik Lorenzen, Morten Rybtke, Jens B. Andersen, Rico Petersen, Paal Skytt Andersen, Thomas E. Nielsen, Tim Tolker-Nielsen, Alain Filloux, Hanne Ingmer, Michael Givskov

^*Corresponding author af dette arbejde

30 Citationer (Scopus)

81 Downloads (Pure)

Abstract

For the last decade, chemical control of bacterial virulence has received considerable attention. Ajoene, a sulfur-rich molecule from garlic has been shown to reduce expression of key quorum sensing regulated virulence factors in the opportunistic pathogen Pseudomonas aeruginosa. Here we show that the repressing effect of ajoene on quorum sensing occurs by inhibition of small regulatory RNAs (sRNA) in P. aeruginosa as well as in Staphylococcus aureus, another important human pathogen that employs quorum sensing to control virulence gene expression. Using various reporter constructs, we found that ajoene lowered expression of the sRNAs RsmY and RsmZ in P. aeruginosa and the small dual-function regulatory RNA, RNAIII in S. aureus, that controls expression of key virulence factors. We confirmed the modulation of RNAIII by RNA sequencing and found that the expression of many QS regulated genes encoding virulence factors such as hemolysins and proteases were lowered in the presence of ajoene in S. aureus. Importantly, our findings show that sRNAs across bacterial species potentially may qualify as targets of anti-virulence therapy and that ajoene could be a lead structure in search of broad-spectrum compounds transcending the Gram negative-positive borderline.

Originalsprog	Engelsk
Artikelnummer	9857
Tidsskrift	Scientific Reports
Vol/bind	7
Udgave nummer	1
Antal sider	12
ISSN	2045-2322
DOI	https://doi.org/10.1038/s41598-017-09886-8
Status	Udgivet - 2017

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10.1038/s41598-017-09886-8Licens: CC BY

A broad range quorum sensing inhibitor working through sRNA inhibitionForlagets udgivne version, 3,71 MBLicens: CC BY

Citationsformater

Jakobsen, T. H., Warming, A. N., Vejborg, R. M., Moscoso, J. A., Stegger, M., Lorenzen, F., Rybtke, M., Andersen, J. B., Petersen, R., Andersen, P. S., Nielsen, T. E., Tolker-Nielsen, T., Filloux, A., Ingmer, H., & Givskov, M. (2017). A broad range quorum sensing inhibitor working through sRNA inhibition. Scientific Reports, 7(1), [9857]. https://doi.org/10.1038/s41598-017-09886-8

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title = "A broad range quorum sensing inhibitor working through sRNA inhibition",

abstract = "For the last decade, chemical control of bacterial virulence has received considerable attention. Ajoene, a sulfur-rich molecule from garlic has been shown to reduce expression of key quorum sensing regulated virulence factors in the opportunistic pathogen Pseudomonas aeruginosa. Here we show that the repressing effect of ajoene on quorum sensing occurs by inhibition of small regulatory RNAs (sRNA) in P. aeruginosa as well as in Staphylococcus aureus, another important human pathogen that employs quorum sensing to control virulence gene expression. Using various reporter constructs, we found that ajoene lowered expression of the sRNAs RsmY and RsmZ in P. aeruginosa and the small dual-function regulatory RNA, RNAIII in S. aureus, that controls expression of key virulence factors. We confirmed the modulation of RNAIII by RNA sequencing and found that the expression of many QS regulated genes encoding virulence factors such as hemolysins and proteases were lowered in the presence of ajoene in S. aureus. Importantly, our findings show that sRNAs across bacterial species potentially may qualify as targets of anti-virulence therapy and that ajoene could be a lead structure in search of broad-spectrum compounds transcending the Gram negative-positive borderline.",

author = "Jakobsen, {Tim H.} and Warming, {Anders N.} and Vejborg, {Rebecca M.} and Moscoso, {Joana A.} and Marc Stegger and Frederik Lorenzen and Morten Rybtke and Andersen, {Jens B.} and Rico Petersen and Andersen, {Paal Skytt} and Nielsen, {Thomas E.} and Tim Tolker-Nielsen and Alain Filloux and Hanne Ingmer and Michael Givskov",

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AU - Jakobsen, Tim H.

AU - Warming, Anders N.

AU - Vejborg, Rebecca M.

AU - Moscoso, Joana A.

AU - Stegger, Marc

AU - Lorenzen, Frederik

AU - Rybtke, Morten

AU - Andersen, Jens B.

AU - Petersen, Rico

AU - Andersen, Paal Skytt

AU - Nielsen, Thomas E.

AU - Tolker-Nielsen, Tim

AU - Filloux, Alain

AU - Ingmer, Hanne

AU - Givskov, Michael

PY - 2017

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N2 - For the last decade, chemical control of bacterial virulence has received considerable attention. Ajoene, a sulfur-rich molecule from garlic has been shown to reduce expression of key quorum sensing regulated virulence factors in the opportunistic pathogen Pseudomonas aeruginosa. Here we show that the repressing effect of ajoene on quorum sensing occurs by inhibition of small regulatory RNAs (sRNA) in P. aeruginosa as well as in Staphylococcus aureus, another important human pathogen that employs quorum sensing to control virulence gene expression. Using various reporter constructs, we found that ajoene lowered expression of the sRNAs RsmY and RsmZ in P. aeruginosa and the small dual-function regulatory RNA, RNAIII in S. aureus, that controls expression of key virulence factors. We confirmed the modulation of RNAIII by RNA sequencing and found that the expression of many QS regulated genes encoding virulence factors such as hemolysins and proteases were lowered in the presence of ajoene in S. aureus. Importantly, our findings show that sRNAs across bacterial species potentially may qualify as targets of anti-virulence therapy and that ajoene could be a lead structure in search of broad-spectrum compounds transcending the Gram negative-positive borderline.

AB - For the last decade, chemical control of bacterial virulence has received considerable attention. Ajoene, a sulfur-rich molecule from garlic has been shown to reduce expression of key quorum sensing regulated virulence factors in the opportunistic pathogen Pseudomonas aeruginosa. Here we show that the repressing effect of ajoene on quorum sensing occurs by inhibition of small regulatory RNAs (sRNA) in P. aeruginosa as well as in Staphylococcus aureus, another important human pathogen that employs quorum sensing to control virulence gene expression. Using various reporter constructs, we found that ajoene lowered expression of the sRNAs RsmY and RsmZ in P. aeruginosa and the small dual-function regulatory RNA, RNAIII in S. aureus, that controls expression of key virulence factors. We confirmed the modulation of RNAIII by RNA sequencing and found that the expression of many QS regulated genes encoding virulence factors such as hemolysins and proteases were lowered in the presence of ajoene in S. aureus. Importantly, our findings show that sRNAs across bacterial species potentially may qualify as targets of anti-virulence therapy and that ajoene could be a lead structure in search of broad-spectrum compounds transcending the Gram negative-positive borderline.

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DO - 10.1038/s41598-017-09886-8

M3 - Journal article

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AN - SCOPUS:85028570198

SN - 2045-2322

VL - 7

JO - Scientific Reports

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A broad range quorum sensing inhibitor working through sRNA inhibition

Abstract

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