Cis-2-decenoic acid modulates Pseudomonas aeruginosa virulence through a noncanonical transcriptional regulator

Shihao Song , Jingyun Liu , Bing Wang , Yang Si , Hongguang Han , Xiuyun Sun , Mingfang Wang , Binbin Cui , Guangliang Wu , Yongliang Huo , Liangxiong Xu , Beile Gao , Liang Yang , Xiaoxue Wang , Lian-Hui Zhang , Yinyue Deng

mLife ›› 2025, Vol. 4 ›› Issue (6) : 623 -637.

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mLife ›› 2025, Vol. 4 ›› Issue (6) :623 -637. DOI: 10.1002/mlf2.70044
ORIGINAL RESEARCH
Cis-2-decenoic acid modulates Pseudomonas aeruginosa virulence through a noncanonical transcriptional regulator
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Abstract

Diffusible signal factor (DSF)-family quorum sensing (QS) signals are widely utilized by many pathogenic bacteria to modulate various biological functions and virulence. Previous studies showed that cis-2-decenoic acid (cis-DA) is involved in the modulation of biofilm dispersion in Pseudomonas aeruginosa, but the regulatory mechanism is unclear. Here, we report that cis-DA regulates the physiology and virulence of P. aeruginosa through FadD1, a long-chain fatty acid-CoA ligase. cis-DA specifically binds to FadD1 and enhances the binding ability of FadD1 to the target gene promoter DNA regions. Further analysis showed that FadD1 is a global regulatory factor that controls the transcription of various target genes. Moreover, FadD1 showed 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 in P. aeruginosa, which is highlighted by the signal receptor evolved from a canonical enzyme of fatty acid metabolism.

Keywords

cis-2-decenoic acid / fatty acid-CoA ligase / Pseudomonas aeruginosa / quorum sensing / virulence

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Shihao Song, Jingyun Liu, Bing Wang, Yang Si, Hongguang Han, Xiuyun Sun, Mingfang Wang, Binbin Cui, Guangliang Wu, Yongliang Huo, Liangxiong Xu, Beile Gao, Liang Yang, Xiaoxue Wang, Lian-Hui Zhang, Yinyue Deng. Cis-2-decenoic acid modulates Pseudomonas aeruginosa virulence through a noncanonical transcriptional regulator. mLife, 2025, 4(6): 623-637 DOI:10.1002/mlf2.70044

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