A comprehensive review of the pathogenic mechanisms of Pseudomonas aeruginosa: synergistic effects of virulence factors, quorum sensing, and biofilm formation
Pseudomonas aeruginosa (P. aeruginosa) is a ubiquitous opportunistic pathogen and a major cause of nosocomial infections worldwide. It can provoke a spectrum of clinical manifestations-ranging from postoperative wound infections, pressure ulcers, abscesses, and otitis media to life-threatening bacte...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2025.1619626/full |
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| author | Xindan Zhang Xindan Zhang Duo Zhang Duo Zhang Di Zhou Di Zhou Shuai Zheng Shuai Zheng Shuang Li Qinlong Hou Qinlong Hou Gen Li Gen Li Huiming Han Huiming Han |
| author_facet | Xindan Zhang Xindan Zhang Duo Zhang Duo Zhang Di Zhou Di Zhou Shuai Zheng Shuai Zheng Shuang Li Qinlong Hou Qinlong Hou Gen Li Gen Li Huiming Han Huiming Han |
| author_sort | Xindan Zhang |
| collection | DOAJ |
| description | Pseudomonas aeruginosa (P. aeruginosa) is a ubiquitous opportunistic pathogen and a major cause of nosocomial infections worldwide. It can provoke a spectrum of clinical manifestations-ranging from postoperative wound infections, pressure ulcers, abscesses, and otitis media to life-threatening bacteremia and sepsis, especially in burn patients. Over the past decade, extensive research has elucidated its complex virulence repertoire, including exotoxins, proteases, and siderophores; the hierarchical Quorum Sensing (QS) networks; and its robust capacity for biofilm formation. In this review, we consolidate significant studies published since 2015 to develop a comprehensive framework elucidating the virulence mechanisms of P. aeruginosa. Beyond cataloging individual factors, we highlight how QS regulators coordinate toxin production and biofilm maturation, and how these processes converge to facilitate immune evasion. We further examine cross-talk between QS circuits (Las, Rhl, and Pqs), their response to environmental cues, and the modulatory role of host signals. Despite these advances, significant gaps remain: the spatiotemporal interplay among different virulence modules; the precise molecular triggers of biofilm dispersal; and the dynamics of bacterial–host immune interactions in vivo. Notably, targeting QS with small-molecule inhibitors has shown promise in attenuating pathogenicity, yet translating these findings into clinical therapies requires more nuanced understanding of resistance emergence and host microbiome effects. We propose that future investigations prioritize (1) the structural biology of QS receptors to guide rational inhibitor design; (2) single-cell and organ-on-a-chip models to dissect biofilm heterogeneity; (3) dual-omics approaches to map host–pathogen signaling crosstalk; and (4) environmental modulators-such as iron availability and shear stress-that fine-tune virulence expression. Such multidisciplinary efforts will underpin the development of next-generation anti-virulence therapies, ultimately improving prevention and treatment of P. aeruginosa infections and safeguarding public health. |
| format | Article |
| id | doaj-art-ee01cdf626d048d796a024652114f514 |
| institution | Kabale University |
| issn | 1664-302X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj-art-ee01cdf626d048d796a024652114f5142025-08-20T03:28:17ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2025-07-011610.3389/fmicb.2025.16196261619626A comprehensive review of the pathogenic mechanisms of Pseudomonas aeruginosa: synergistic effects of virulence factors, quorum sensing, and biofilm formationXindan Zhang0Xindan Zhang1Duo Zhang2Duo Zhang3Di Zhou4Di Zhou5Shuai Zheng6Shuai Zheng7Shuang Li8Qinlong Hou9Qinlong Hou10Gen Li11Gen Li12Huiming Han13Huiming Han14The School of Basic Medicine, Beihua University, Jilin, ChinaThe Center for Infection and Immunity, Beihua University, Jilin, ChinaThe School of Basic Medicine, Beihua University, Jilin, ChinaThe Center for Infection and Immunity, Beihua University, Jilin, ChinaThe School of Basic Medicine, Beihua University, Jilin, ChinaThe Center for Infection and Immunity, Beihua University, Jilin, ChinaThe School of Basic Medicine, Beihua University, Jilin, ChinaThe Center for Infection and Immunity, Beihua University, Jilin, ChinaDepartment of Science and Education, Affiliated Hospital of Beihua University, Jilin, ChinaThe School of Basic Medicine, Beihua University, Jilin, ChinaThe Center for Infection and Immunity, Beihua University, Jilin, ChinaThe School of Basic Medicine, Beihua University, Jilin, ChinaThe Center for Infection and Immunity, Beihua University, Jilin, ChinaThe School of Basic Medicine, Beihua University, Jilin, ChinaThe Center for Infection and Immunity, Beihua University, Jilin, ChinaPseudomonas aeruginosa (P. aeruginosa) is a ubiquitous opportunistic pathogen and a major cause of nosocomial infections worldwide. It can provoke a spectrum of clinical manifestations-ranging from postoperative wound infections, pressure ulcers, abscesses, and otitis media to life-threatening bacteremia and sepsis, especially in burn patients. Over the past decade, extensive research has elucidated its complex virulence repertoire, including exotoxins, proteases, and siderophores; the hierarchical Quorum Sensing (QS) networks; and its robust capacity for biofilm formation. In this review, we consolidate significant studies published since 2015 to develop a comprehensive framework elucidating the virulence mechanisms of P. aeruginosa. Beyond cataloging individual factors, we highlight how QS regulators coordinate toxin production and biofilm maturation, and how these processes converge to facilitate immune evasion. We further examine cross-talk between QS circuits (Las, Rhl, and Pqs), their response to environmental cues, and the modulatory role of host signals. Despite these advances, significant gaps remain: the spatiotemporal interplay among different virulence modules; the precise molecular triggers of biofilm dispersal; and the dynamics of bacterial–host immune interactions in vivo. Notably, targeting QS with small-molecule inhibitors has shown promise in attenuating pathogenicity, yet translating these findings into clinical therapies requires more nuanced understanding of resistance emergence and host microbiome effects. We propose that future investigations prioritize (1) the structural biology of QS receptors to guide rational inhibitor design; (2) single-cell and organ-on-a-chip models to dissect biofilm heterogeneity; (3) dual-omics approaches to map host–pathogen signaling crosstalk; and (4) environmental modulators-such as iron availability and shear stress-that fine-tune virulence expression. Such multidisciplinary efforts will underpin the development of next-generation anti-virulence therapies, ultimately improving prevention and treatment of P. aeruginosa infections and safeguarding public health.https://www.frontiersin.org/articles/10.3389/fmicb.2025.1619626/fullPseudomonas aeruginosavirulence factorsquorum sensingbiofilmimmune evasion |
| spellingShingle | Xindan Zhang Xindan Zhang Duo Zhang Duo Zhang Di Zhou Di Zhou Shuai Zheng Shuai Zheng Shuang Li Qinlong Hou Qinlong Hou Gen Li Gen Li Huiming Han Huiming Han A comprehensive review of the pathogenic mechanisms of Pseudomonas aeruginosa: synergistic effects of virulence factors, quorum sensing, and biofilm formation Frontiers in Microbiology Pseudomonas aeruginosa virulence factors quorum sensing biofilm immune evasion |
| title | A comprehensive review of the pathogenic mechanisms of Pseudomonas aeruginosa: synergistic effects of virulence factors, quorum sensing, and biofilm formation |
| title_full | A comprehensive review of the pathogenic mechanisms of Pseudomonas aeruginosa: synergistic effects of virulence factors, quorum sensing, and biofilm formation |
| title_fullStr | A comprehensive review of the pathogenic mechanisms of Pseudomonas aeruginosa: synergistic effects of virulence factors, quorum sensing, and biofilm formation |
| title_full_unstemmed | A comprehensive review of the pathogenic mechanisms of Pseudomonas aeruginosa: synergistic effects of virulence factors, quorum sensing, and biofilm formation |
| title_short | A comprehensive review of the pathogenic mechanisms of Pseudomonas aeruginosa: synergistic effects of virulence factors, quorum sensing, and biofilm formation |
| title_sort | comprehensive review of the pathogenic mechanisms of pseudomonas aeruginosa synergistic effects of virulence factors quorum sensing and biofilm formation |
| topic | Pseudomonas aeruginosa virulence factors quorum sensing biofilm immune evasion |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2025.1619626/full |
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