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. 2025 Nov 19:15:1624927.
doi: 10.3389/fcimb.2025.1624927. eCollection 2025.

The role of cyano-phycocyanin as a quorum sensing inhibitor to attenuate Pseudomonas aeruginosa virulence

Jun Ying  1 , Shiqun Guo  1 , Yunru Pan  2 , Dong Li  1 , Yijia Tai  1 , Yue Li  1 , Qinyu Lin  1 , Lingling Pan  3 , Dadao Huang  3 , Hanqi Xiao  3 , Ruowang Pan  3 , Xiaomin Xu  4 , Jing Xie  4 , Zhefeng Lou  1 , Peizhen Li  1
Affiliations

The role of cyano-phycocyanin as a quorum sensing inhibitor to attenuate Pseudomonas aeruginosa virulence

Jun Ying et al. Front Cell Infect Microbiol. .

Abstract

Introduction: In recent years, developing drugs that directly target pathways related to the pathogenic mechanisms of bacteria has been a research hotspot, and quorum sensing (QS) is one of the most effective strategies to combat multidrug-resistant bacteria. We evaluated the inhibitory effect of cyano-phycocyanin (C-PC) on the virulence of PA2 in vitro and in vivo and explored its potential as a quorum sensing inhibitor (QSI).

Methods: In this study, the minimum inhibitory concentration (MIC) and growth curve of C-PC on PA2 were determined, and the effect of C-PC on QS-regulated virulence factors and the anti-biofilm activity of C-PC against PA2 were investigated. The Pseudomonas quinolone signal (PQS) were analyzed by HPLC system and the expression levels of QS signaling molecules, virulence genes, biofilm and movement-related genes were detected by qPCR. The macrophage and mouse infection model were used to explore the anti-infection ability of C-PC in vitro and in vivo.

Results: C-PC attenuated biofilm formation, pyocyanin synthesis, motility, and PQS signaling molecule production. Moreover, C-PC significantly downregulated the transcription levels of QS-related genes in PA2, including pqsA and pqsR, as well as the expression of virulence factor genes phzA, lasA, lasB, flgF, fliE, exoS, exsA, lecA, popB, vasG, chiC, pelF, pslB, qseB, and pgsR. In vitro, C-PC reduced the adhesion and invasion of PA2 in RAW264.7 cells, and decreased LDH release and macrophage damage caused by PA2 infection. In vivo, C-PC reduced the pathogenicity of PA2 and improved mouse survival rates, showing a protective effect.

Conclusion: Taken together, these results suggest that C-PC showed strong anti-QS activity, providing new insights into the development of strategies against PA infection.

Keywords: C-PC; PQS; Pseudomonas aeruginosa; RAW264.7; biofilm.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Effects of different concentrations of C-PC on the growth of PA2. All data were expressed as means ± SD (n = 3). **P < 0.01 versus the untreated control group.
Figure 2
Figure 2
Effect of sub-MICs of C-PC on inhibition of pyocyanin production in PA2. All data were expressed as means ± SD (n = 3). **P < 0.01 versus the untreated control group.
Figure 3
Figure 3
Effect of sub-MICs of C-PC on inhibition of motility in PA2. (a, b) The swimming and swarming diameter statistics. All data were expressed as means ± SD (n = 3). *P < 0.05 and **P < 0.01 versus the untreated control group. (c) Swimming motility. (d) Swarming motility.
Figure 4
Figure 4
Effects of C-PC on biofilm formation of PA2 at different concentrations. (a) The biofilm quantified by crystal violet staining and measuring at A570 nm. (b) Light microscopic images. All data were expressed as means ± SD (n = 3). **P < 0.01 versus the untreated control group.
Figure 5
Figure 5
Effect of C-PC on inhibition of PQS production in PA2 analysied by HPLC assays. All data were expressed as means ± SD (n = 3). **P < 0.01 versus the PA2.
Figure 6
Figure 6
Transcriptional levels of the QS-related (a) and virulence genes (b) in PA2 with different concentrations C-PC for compared with untreated control detected by qPCR. All data were expressed as means ± SD (n = 3). *P < 0.05, **P < 0.01 versus the untreated control group.
Figure 7
Figure 7
Effects of C-PC on adhesion and invasion of PA2 infected RAW264.7 cells. (a) Effect of different concentrations of C-PC on RAW264.7 cell viability activity. (b) The adhesion of PA2 infected RAW264.7 cells. (c) The invasion of PA2 infected RAW264.7 cells. (d) Effects of C-PC on LDH activity of RAW264.7 cells infected with PA2. All data were expressed as means ± SD (n = 3). *P < 0.05, **P < 0.01 versus the untreated control group. ##P < 0.01 versus the PA2 group.
Figure 8
Figure 8
Effects of C-PC on the virulence of PA2 in a mouse model. (a) Mouse survival rate. (b) H&E staining of the heart, liver, spleen, lung, and kidney tissues.
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