The long-chain fatty acid-CoA ligase FadD1 monitors Pseudomonas aeruginosa quorum sensing as a receptor of cis-2-decenoic acid

Song, S.; Li, X.; Liu, J.; Wang, B.; Si, Y.; Han, H.; Sun, X.; Wang, M.; Cui, B.; Wu, G.; Huo, Y.; Xu, L.; Gao, B.; Yang, L.; Wang, X.; Zhang, L.; Deng, Y.

doi:10.1101/2024.06.08.598097

bioRxiv · 10.1101/2024.06.08.598097

The long-chain fatty acid-CoA ligase FadD1 monitors Pseudomonas aeruginosa quorum sensing as a receptor of cis-2-decenoic acid

Song, S.·Li, X.·Liu, J.·Wang, B.·Si, Y.·Han, H.·Sun, X.·Wang, M.·Cui, B.·Wu, G.·Huo, Y.·Xu, L.·Gao, B.·Yang, L.·Wang, X.·Zhang, L.·Deng, Y.

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Abstract

Diffusible signal factor (DSF)-family quorum sensing (QS) signals are widely utilized by many bacterial pathogens to modulate various biological functions and virulence. Previous studies showed that cis-2-decenoic acid (cis-DA) is involved in modulation of biofilm dispersion in Pseudomonas aeruginosa, but its signaling mechanism remains vague. Here, we report that cis-DA regulates the physiology and virulence of P. aeruginosa through the long-chain fatty acid-CoA ligase FadD1. Cis-DA specifically binds to FadD1 with high affinity and enhances the binding of FadD1 to the promoter DNA region of lasR. Further analysis showed that the FadD1 is a response regulator of cis-DA with a DNA-binding leucine zipper motif to control the transcription of various target genes. Moreover, FadD1 exhibited catalytic activity on cis-2-dodecenoic acid (BDSF) of Burkholderia cenocepacia and enhanced the competitiveness of P. aeruginosa. Together, our work presents a new DSF-type QS signaling system, which is highlighted by its receptor and response regulator evolved from a canonical enzyme of fatty acid metabolism. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=135 SRC="FIGDIR/small/598097v2_ufig1.gif" ALT="Figure 1"> View larger version (15K): org.highwire.dtl.DTLVardef@66b8aaorg.highwire.dtl.DTLVardef@1e5b9b9org.highwire.dtl.DTLVardef@1043525org.highwire.dtl.DTLVardef@13d3ed1_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsThe long-chain fatty acid-CoA ligase FadD1 acts as a global transcriptional regulator in P. aeruginosa. FadD1 is a receptor of QS signal cis-DA and functions at the top of the QS hierarchy in P. aeruginosa. The homolog of FadD1 in P. fluorescens could bind to the target gene promoter by responding to cis-DA. In briefPseudomonas aeruginosa is a human pathogen with antibiotic resistance and a wide range of dynamic defenses makes it an extremely challenging organism to treat in modern-day medicine. It employs cis-2-decenoic acid (cis-DA) quorum sensing to regulate the physiology and pathogenesis. Song et al. demonstrate that the long-chain fatty acid-CoA ligase FadD1 controls the important biological functions and virulence in P. aeruginosa as a novel response regulator of cis-DA signal.

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Song, S., Li, X., Liu, J., Wang, B., Si, Y., Han, H., Sun, X., Wang, M., Cui, B., Wu, G., Huo, Y., Xu, L., Gao, B., Yang, L., Wang, X., Zhang, L., Deng, Y.. 2024-06-09. The long-chain fatty acid-CoA ligase FadD1 monitors Pseudomonas aeruginosa quorum sensing as a receptor of cis-2-decenoic acid. https://doi.org/10.1101/2024.06.08.598097

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