As the antibiotic resistance of pathogens becomes increasingly severe, it is becoming more feasible to use methods that suppress the virulence of pathogens rather than exerting selective pressure on their growth. Pseudomonas aeruginosa, a dangerous opportunistic pathogen, infects hosts by producing multiple virulence factors, which are regulated by quorum-sensing (QS) systems, including the las systems, rhl systems, and pqs systems. This study used the chromosome lacZ transcription fusion reporter model to screen the traditional Chinese medicine monomer library and found that bakuchiol can effectively inhibit the pqs system and related virulence phenotypes of P. aeruginosa, including the production of virulence factors (pyocyanin, hydrogen cyanide, elastase, and lectin) and motility (swarming, swimming, and twitching motility) without affecting its growth. Subsequently, through genetic complementation analysis, we found that bakuchiol inhibited the function of the transcriptional activation protein PqsR of the pqs system in P. aeruginosa in a concentration-dependent manner. Furthermore, molecular dynamics simulation study results indicated that bakuchiol can target PqsR of the pqs system, thereby inhibiting the pqs system. Among the amino acids in PqsR, ALA-168 may be a key amino acid residue in the hydrophobic interaction between PqsR protein and bakuchiol. Finally, in vivo experiments demonstrated that bakuchiol attenuated the pathogenicity of P. aeruginosa to Chinese cabbage (Brassica pekinensis) and Caenorhabditis elegans. In summary, this study suggests that bakuchiol is an effective inhibitor that targets the pqs system of P. aeruginosa, providing a new strategy for addressing P. aeruginosa infections.

Plant fungal diseases, such as apple tree canker caused by Valsa mali, have caused severe losses in agricultural production. Traditional chemical fungicides induce drug resistance in pathogens and cause environmental pollution. Therefore, it is of substantial importance to screen efficient and environmentally friendly bacterial strains as potential biocontrol agents. The tea rhizosphere harbors abundant microbial resources, and previous research has identified microorganisms with antifungal activity existing in this environment. Therefore, in this study, we isolated antagonistic bacteria with broad-spectrum biocontrol potential from tea rhizosphere soil. In this study, a strain with strong antagonistic activity against V. mali was isolated from tea rhizosphere soil. Based on morphological characteristics, 16S rRNA gene sequencing, and whole-genome analysis, the isolated strain was identified as Bacillus velezensis and designated as LW-66. This strain demonstrated broad-spectrum antifungal activity against various plant pathogenic fungi, including Valsa mali, Fusarium graminearum, Bipolaris sorokinianum, Alternaria solani, and Exserohilum turcicum. The active extract of B. velezensis maintained strong stability across a wide range of temperatures (25–90 °C) and pH values (2–8), with stability decreasing only when the temperature reached 100 °C or pH ≥ 10. In a preventive assay using detached apple branches inoculated with V. mali, the control efficacy of LW-66 against apple tree canker reached more than 90%. Additionally, in a therapeutic assay using V. mali-infected potted apple seedlings, the LW-66 bone-glue bacterial agent achieved a survival rate of up to 90%. Whole-genome analysis revealed that the genome of LW-66 contains 13 predicted secondary metabolite biosynthetic gene clusters, seven of which showed high homology (≥92% similarity) with known antimicrobial gene clusters, including surfactin, bacillaene, macrolactin H, fengycin, difficidin, bacillibactin, and bacilysin. These gene clusters may be connected to the broad-spectrum antifungal activity of B. velezensis, as well as its ability to disrupt hyphal morphology. The volatile organic compounds produced by LW-66 inhibited V. mali growth by 91.70%. Collectively, these findings demonstrate that B. velezensis LW-66 has a wide antimicrobial range and strong antagonistic effects against multiple plant pathogenic fungi. Therefore, B. velezensis shows promise as a biocontrol agent for managing fungal diseases in plants, providing a basis for developing LW-66-derived biocontrol products aimed at controlling diseases such as apple tree canker.

Pseudomonas aeruginosa is a common Gram-negative bacterium in hospital infections and one of the main pathogens causing opportunistic infections in humans. In recent years, the drug resistance of P. aeruginosa has become increasingly severe. Therefore, it is urgent to explore new targets for antibacterial therapy. In P. aeruginosa, iron is an essential element not only for cell growth but also for successful infection. Two siderophores are produced by P. aeruginosa: pyoverdine and pyochelin. They help P. aeruginosa to obtain iron and play an important role in interspecific competition, anti-oxidative stress, and virulence. Furthermore, siderophores have been used to design “Trojan horse” antibiotics. These antibiotic–siderophore conjugates enter the cytoplasm of P. aeruginosa via siderophore uptake systems for pyoverdine and pyochelin, releasing antibacterial substances and exerting corresponding effects against P. aeruginosa. This review discusses the synthesis, secretion, and uptake of siderophores in P. aeruginosa as well as the role of the “Trojan horse” strategy in treating P. aeruginosa infections.

Pseudomonas aeruginosa, an opportunistic pathogen, is a major threat to hospital infection control and global public health due to its strong environmental adaptability, complex virulence systems, efficient biofilm formation capability, and widespread multidrug resistance. Traditional single-target antibiotics are often inadequate for clinical treatment. The research into Plant-Derived Bioactive Compounds for combating P. aeruginosa infections is reviewed, highlighting their advantages (many of which are extensively studied in Traditional Chinese Medicine) over conventional antibiotics. The antimicrobial mechanisms of these compounds include the inhibition of bacterial quorum sensing (QS) systems to suppress virulence factor expression rather than direct anti-bactericidal effects, delaying the development of resistance. The abundant natural medicinal plants and their diverse chemical structures provide ample material for active compound screening to identify unique chemical compositions with specific binding to pathogen targets. Plant-Derived Bioactive Compounds exhibit excellent safety profiles, targeting bacterial-specific pathways or host immune regulation, resulting in minimal off-target toxicity. Plant-Derived Bioactive Compounds exert anti-P. aeruginosa effects via inhibition of QS systems to reduce pathogenicity by disrupting intercellular signaling, suppressing biofilm formation/maturity to overcome biofilm-associated resistance, directly interacting with bacterial structure. Plant-Derived Bioactive Compounds are promising treatments for drug-resistant P. aeruginosa infections, providing lead compounds for novel anti-infective drug development.