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Cis-2-dodecenoic acid signal modulates virulence of Pseudomonas aeruginosa through interference with quorum sensing systems and T3SS.

Deng Y, Boon C, Chen S, Lim A, Zhang LH - BMC Microbiol. (2013)

Bottom Line: Furthermore, BDSF and some of its derivatives are also capable of inhibiting T3SS of P. aeruginosa at a micromolar level.Treatment with BDSF obviously reduced the virulence of P. aeruginosa in both HeLa cell and zebrafish infection models.These results depict that BDSF modulates virulence of P. aeruginosa through interference with QS systems and T3SS.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Molecular and Cell Biology, Proteos, 61 Biopolis Drive, Singapore, 138673, Singapore. ydeng@imcb.a-star.edu.sg.

ABSTRACT

Background: Cis-2-dodecenoic acid (BDSF) is well known for its important functions in intraspecies signaling in Burkholderia cenocepacia. Previous work has also established an important role of BDSF in interspecies and inter-kingdom communications. It was identified that BDSF modulates virulence of Pseudomonas aeruginosa. However, how BDSF interferes with virulence of P. aeruginosa is still not clear.

Results: We report here that BDSF mediates the cross-talk between B. cenocepacia and P. aeruginosa through interference with quorum sensing (QS) systems and type III secretion system (T3SS) of P. aeruginosa. Bioassay results revealed that exogenous addition of BDSF not only reduced the transcriptional expression of the regulator encoding gene of QS systems, i.e., lasR, pqsR, and rhlR, but also simultaneously decreased the production of QS signals including 3-oxo-C12-HSL, Pseudomonas quinolone signal (PQS) and C4-HSL, consequently resulting in the down-regulation of biofilm formation and virulence factor production of P. aeruginosa. Furthermore, BDSF and some of its derivatives are also capable of inhibiting T3SS of P. aeruginosa at a micromolar level. Treatment with BDSF obviously reduced the virulence of P. aeruginosa in both HeLa cell and zebrafish infection models.

Conclusions: These results depict that BDSF modulates virulence of P. aeruginosa through interference with QS systems and T3SS.

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Related in: MedlinePlus

The inhibitory activity on T3SS of P. aeruginosa PA14 is conserved in BDSF derivatives. (A) Effect of exogenous addition of 10 μM BDSF and its derivatives on T3SS genes expression, as determined by using PexsCEBA-lacZ fusion reporter strain. “T” means the fatty acids with trans configuration; while “C” means the fatty acids with cis configuration; number represents the carbon chain length. Their structures were listed in Table S1. (B) BDSF (C12) showed the strongest activity than its saturated isomer (S12) and trans-isomer (T12). Bacteria were grown in LB medium supplemented with 5 mM NTA to an OD600 of ~1.5. The data are the means of three repeats and error bars indicate the standard deviations.
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Figure 5: The inhibitory activity on T3SS of P. aeruginosa PA14 is conserved in BDSF derivatives. (A) Effect of exogenous addition of 10 μM BDSF and its derivatives on T3SS genes expression, as determined by using PexsCEBA-lacZ fusion reporter strain. “T” means the fatty acids with trans configuration; while “C” means the fatty acids with cis configuration; number represents the carbon chain length. Their structures were listed in Table S1. (B) BDSF (C12) showed the strongest activity than its saturated isomer (S12) and trans-isomer (T12). Bacteria were grown in LB medium supplemented with 5 mM NTA to an OD600 of ~1.5. The data are the means of three repeats and error bars indicate the standard deviations.

Mentions: It was revealed that structural features of fatty acids molecules may contribute to their biological activity [4,37,58]. To investigate whether BDSF derivatives share the inhibitory activity on T3SS of P. aeruginosa, and study the interaction between structural features and inhibitory activities of DSF-family molecules on T3SS, a series of BDSF derivatives with different structures (Additional file 1: Table S1) were applied to test their effect on the transcriptional expression of exsCEBA. The T3SS reporter strain, PexsCEBA-lacZ, was refreshed and cultured in LB medium supplemented with 5 mM NTA. BDSF and its derivatives were added at a final concentration of 10 μM. Beta-gal activity was measured when the cultures reached an OD600 of ~1.5. Bioassays results revealed that α,β-unsaturated fatty acids with chain length more than twelve showed a significant inhibition on T3SS gene expression (Figure 5). Moreover, it was indicated that configuration of BDSF derivatives contributes to their inhibitory activity; and cis-conformational fatty acids showed the strongest inhibitory activity, followed by their saturated isomers and trans-isomers (Figure 5B). Additionally, methyl group substitution and chain length could also affect the inhibitory activity (Figure 5A).


Cis-2-dodecenoic acid signal modulates virulence of Pseudomonas aeruginosa through interference with quorum sensing systems and T3SS.

Deng Y, Boon C, Chen S, Lim A, Zhang LH - BMC Microbiol. (2013)

The inhibitory activity on T3SS of P. aeruginosa PA14 is conserved in BDSF derivatives. (A) Effect of exogenous addition of 10 μM BDSF and its derivatives on T3SS genes expression, as determined by using PexsCEBA-lacZ fusion reporter strain. “T” means the fatty acids with trans configuration; while “C” means the fatty acids with cis configuration; number represents the carbon chain length. Their structures were listed in Table S1. (B) BDSF (C12) showed the strongest activity than its saturated isomer (S12) and trans-isomer (T12). Bacteria were grown in LB medium supplemented with 5 mM NTA to an OD600 of ~1.5. The data are the means of three repeats and error bars indicate the standard deviations.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4016476&req=5

Figure 5: The inhibitory activity on T3SS of P. aeruginosa PA14 is conserved in BDSF derivatives. (A) Effect of exogenous addition of 10 μM BDSF and its derivatives on T3SS genes expression, as determined by using PexsCEBA-lacZ fusion reporter strain. “T” means the fatty acids with trans configuration; while “C” means the fatty acids with cis configuration; number represents the carbon chain length. Their structures were listed in Table S1. (B) BDSF (C12) showed the strongest activity than its saturated isomer (S12) and trans-isomer (T12). Bacteria were grown in LB medium supplemented with 5 mM NTA to an OD600 of ~1.5. The data are the means of three repeats and error bars indicate the standard deviations.
Mentions: It was revealed that structural features of fatty acids molecules may contribute to their biological activity [4,37,58]. To investigate whether BDSF derivatives share the inhibitory activity on T3SS of P. aeruginosa, and study the interaction between structural features and inhibitory activities of DSF-family molecules on T3SS, a series of BDSF derivatives with different structures (Additional file 1: Table S1) were applied to test their effect on the transcriptional expression of exsCEBA. The T3SS reporter strain, PexsCEBA-lacZ, was refreshed and cultured in LB medium supplemented with 5 mM NTA. BDSF and its derivatives were added at a final concentration of 10 μM. Beta-gal activity was measured when the cultures reached an OD600 of ~1.5. Bioassays results revealed that α,β-unsaturated fatty acids with chain length more than twelve showed a significant inhibition on T3SS gene expression (Figure 5). Moreover, it was indicated that configuration of BDSF derivatives contributes to their inhibitory activity; and cis-conformational fatty acids showed the strongest inhibitory activity, followed by their saturated isomers and trans-isomers (Figure 5B). Additionally, methyl group substitution and chain length could also affect the inhibitory activity (Figure 5A).

Bottom Line: Furthermore, BDSF and some of its derivatives are also capable of inhibiting T3SS of P. aeruginosa at a micromolar level.Treatment with BDSF obviously reduced the virulence of P. aeruginosa in both HeLa cell and zebrafish infection models.These results depict that BDSF modulates virulence of P. aeruginosa through interference with QS systems and T3SS.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Molecular and Cell Biology, Proteos, 61 Biopolis Drive, Singapore, 138673, Singapore. ydeng@imcb.a-star.edu.sg.

ABSTRACT

Background: Cis-2-dodecenoic acid (BDSF) is well known for its important functions in intraspecies signaling in Burkholderia cenocepacia. Previous work has also established an important role of BDSF in interspecies and inter-kingdom communications. It was identified that BDSF modulates virulence of Pseudomonas aeruginosa. However, how BDSF interferes with virulence of P. aeruginosa is still not clear.

Results: We report here that BDSF mediates the cross-talk between B. cenocepacia and P. aeruginosa through interference with quorum sensing (QS) systems and type III secretion system (T3SS) of P. aeruginosa. Bioassay results revealed that exogenous addition of BDSF not only reduced the transcriptional expression of the regulator encoding gene of QS systems, i.e., lasR, pqsR, and rhlR, but also simultaneously decreased the production of QS signals including 3-oxo-C12-HSL, Pseudomonas quinolone signal (PQS) and C4-HSL, consequently resulting in the down-regulation of biofilm formation and virulence factor production of P. aeruginosa. Furthermore, BDSF and some of its derivatives are also capable of inhibiting T3SS of P. aeruginosa at a micromolar level. Treatment with BDSF obviously reduced the virulence of P. aeruginosa in both HeLa cell and zebrafish infection models.

Conclusions: These results depict that BDSF modulates virulence of P. aeruginosa through interference with QS systems and T3SS.

Show MeSH
Related in: MedlinePlus