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Chromobacterium violaceum, one free-living Gram-negative bacterium, is abundantly presented in tropics and sub-tropics soil and aquatic environment; it is also an opportunistic human pathogen. Here, two cinnamic acid derivatives, i.e., 4-dimethylaminocinnamic acid (DCA) and 4-methoxycinnamic acid (MCA), were identified as potential quorum sensing (QS) and biofilm inhibitors in C. violaceum ATCC12472. Both DCA (100 μg/mL) and MCA (200 μg/mL) inhibited the levels of N-decanoyl-homoserine lactone (C10-HSL) and reduced the production of certain virulence factors in C. violaceum, including violacein, hemolysin, and chitinase. Metabolomics analysis indicated that QS-related metabolites, such as ethanolamine and L-methionine, were down-regulated after treatment with DCA and MCA. Quantitative real-time polymerase chain reaction (qRT-PCR) demonstrated that DCA and MCA markedly suppressed the expression of two QS-related genes (cviI and cviR). In addition, DCA and MCA also inhibited biofilm formation and enhanced the susceptibility of biofilms to tobramycin, which was evidenced by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). Our results indicated that DCA and MCA can serve as QS-based agent for controlling pathogens.Key Points• DCA and MCA inhibited QS and biofilm formation in C. violaceum.• The combination of DCA or MCA and tobramycin removed the preformed biofilm of C. violaceum.• DCA or MCA inhibited virulence factors and expressions of cviI and cviR of C. violaceum.• DCA or MCA are potential antibiotic accelerants for treating C. violaceum infection.

Quorum sensing (QS) and clustered regularly interspaced short palindromic repeats (CRISPR) systems are envisaged as revolutionary in abating plant bacterial pathogens. Bacterial cell-cell communication and plant pathogen QSSMs (quorum sensing signaling molecules) are dissected for underlying mechanisms in prominent pathogens, viz., , nd . Biofilm formation and virulence mechanisms are critically addressed to repurpose potential QS inhibition strategies. CRISPR technologies are combined with CRISPR engineering to produce enhanced disease-resistant varieties, with potential applications. QS-CRISPR interplay for deciphering the key interactive changes in plant health management is prioritized for deliberate future research outcomes. Sustainable agricultural practices are envisaged for successful lab-to-field authentic field trials and large-scale applicability across the globe. Potential technical limitations, the need for stringent agricultural laws, and future innovations are addressed. Moreover, the cost-effectiveness, enhanced crop production, yield, and productivity hindering the above key plant bacterial pathogens are comprehensively addressed against these plant bacterial pathogens. Furthermore, a future outlook characterized by extensive outreach and global implications is substantiated regardless of regional specificity, climate change, and global warming. A decade of research on advancements in adequate plant protection is revisited to incorporate augmented approaches, including artificial intelligence (AI) and machine learning, in sustainable agriculture. The significance of the present review is based on addressing QSSMs and plant protection strategies encompassing modern molecular biological techniques.

The activation of C—C bonds enables rapid construction of new organic frameworks owing to facile structural reorganization. Nevertheless, enantioselective C—C activation remains heavily underexplored and has been predominantly limited to intramolecular reactions. We herein report two categories of asymmetric intermolecular [4 + 2] annulations between benzocyclobutenones (BCBs) and unsaturated reagents, namely, alkynes and cyclic dicarbonyl compounds. The atroposelective coupling of BCB with several classes of sterically hindered alkynes afford C—N and C—C axially chiral 2-naphthols. The [4 + 2] annulation of BCBs and α -dicarbonyls afford spirocyclic products. Both coupling systems proceed efficiently with excellent regio-, chemo- and enantioselectivity via substrate activation and judicious choice of chiral bidentate phosphine ligands. Synthetic transformations of selected products are demonstrated, and the derived chiral products are shown to be useful additives in C—H bond activation or as ligands in Pd-catalyzed C—C coupling. Enantioselective C—C activation remains heavily underexplored and has been predominantly limited to intramolecular reactions. Here the authors report two categories of asymmetric intermolecular [4+2] annulations between benzocyclobutenones and unsaturated reagents, namely, alkynes and cyclic dicarbonyl compounds.

Camellia nitidissima Chi (CNC) is a valuable medicinal and edible plant in China. In this study, CNC flowers were extracted with 95% ethanol, then partitioned into dichloromethane, ethyl acetate, n-butanol, and water fractions, with the antioxidant capacity of flavonoids and other phytochemicals in CNC flowers investigated for the first time. Results showed that the ethyl acetate fraction exhibited the strongest antioxidant capacity and highest total phenolic content (TPC) compared with the other fractions. Furthermore, in the ethyl acetate fraction, the 50% effective concentrations (EC50) of ABTS+ and DPPH radical scavenging activities were 64.24 ± 1.80 and 78.80 ± 0.34 μg/mL, respectively, and the ferric reducing antioxidant power (FRAP) was 801.49 ± 2.30 μM FeSO4 at 1,000 μg/mL. Pearson's correlation coefficients and principal component analyses (PCA) for the TPC and antioxidant capacity of the five fractions indicated that the phenolic compounds were the major antioxidant constituents in the flowers. To exploit the antioxidants in CNC flowers, 21 phenolic compounds in the ethanolic extract fraction were identified by HPLC Triple TOF MS/MS, next, 12 flavonoids were isolated and elucidated, of which compounds 1-5 showed potent antioxidant capacity. In addition, the potential structure-activity relationship among these 12 flavonoids showed that (1) the o-catechol group in the B-ring was primarily responsible for the antioxidant capacity of flavonoids and (2) steric hindrance, produced by glycosides and other groups, could reduce the antioxidant capacity of the flavonoids.

Proton magnetic resonance–based metabolomics analysis was performed to determine the global metabolite changes in pathogenic bacterium Pseudomonas aeruginosa PAO1 following exposure to quorum sensing (QS) inhibitor hordenine. Pyocyanin inhibition assay confirmed that hordenine exhibited potent QS inhibitory activity. A total of 40 metabolites were assigned by PMR spectra. Hordenine treatment resulted in the destruction of QS system in P. aeruginosa PAO1 by downregulating the expressions of genes involved in QS. The synthesis of antioxidant enzymes was repressed and the oxidative stress was enhanced due to the dysfunctional QS system of P. aeruginosa PAO1. The enhanced oxidative stress induced by the dysfunctional QS system of P. aeruginosa PAO1 altered the membrane components, enhanced membrane permeability, and disturbed energy metabolism, amino acid metabolism, and nucleotide metabolism, and would ultimately attenuate the pathogenicity of P. aeruginosa PAO1. Hordenine may have promising potential for controlling nosocomial pathogens.

Phomopsis liquidambari S47 is an endophytic fungus isolated from the leaves of Punica granatum. Here, we are the first to report a quorum sensing (QS) inhibitor 1-(4-amino-2-hydroxyphenyl)ethanone (AHE) isolated and identified from the metabolites of P. liquidambari S47. Exposure to AHE at sub-MIC concentrations notably suppressed the secretion of acyl-homoserine lactones and virulence factors in Pseudomonas aeruginosa PAO1. To investigate the metabolic variations of P. aeruginosa PAO1 exposed to AHE, magnetic resonance imaging-based metabolomic analysis was performed. AHE treatment created a disturbance in the QS system by suppressing the expressions of QS-related genes. The disturbed QS system resulted in the inhibited activity of antioxidant enzymes and thus enhanced oxidative stress. The vegetable infection assay showed that the virulence of P. aeroginosa PAO1 was attenuated which could be due to the impacts to the amino acid and nucleotide metabolism by enhanced oxidative stress. These findings suggest that AHE has a potential to become an antivirulence “agent” to tackle P. aeruginosa infection.Key points• AHE treatment inhibited AHL secretion and virulence factors production.• AHE treatment aggravated oxidative stress and disturbed metabolism.• AHE suppressed QS-related gene expressions and reduced virulence of P. aeruginosa.

Bacillus cereus, a common food-borne pathogen, forms biofilms and generates virulence factors through a quorum sensing (QS) mechanism. In this study, six compounds (dankasterone A, demethylincisterol A3, zinnimidine, cyclo-(L-Val-L-Pro), cyclo-(L-Ile-L-Pro), and cyclo-(L-Leu-L-Pro)) were isolated from the endophytic fungus Pithomyces sacchari of the Laurencia sp. in the South China Sea. Among them, demethylincisterol A3, a sterol derivative, exhibited strong QS inhibitory activity against B. cereus. The QS inhibitory activity of demethylincisterol A3 was evaluated through experiments. The minimum inhibitory concentration (MIC) of demethylincisterol A3 against B. cereus was 6.25 μg/mL. At sub-MIC concentrations, it significantly decreased biofilm formation, hindered mobility, and diminished the production of protease and hemolysin activity. Moreover, RT-qPCR results demonstrated that demethylincisterol A3 markedly inhibited the expression of QS-related genes (plcR and papR) in B. cereus. The exposure to demethylincisterol A3 resulted in the downregulation of genes (comER, tasA, rpoN, sinR, codY, nheA, hblD, and cytK) associated with biofilm formation, mobility, and virulence factors. Hence, demethylincisterol A3 is a potentially effective compound in the pipeline of innovative antimicrobial therapies.

Pseudomonas aeruginosa is a ubiquitous pathogen that is the leading cause of chronic infections. Bacterial biofilm formation facilitates CF development and restricts the anti-bacterial potential of many current antibiotics. The capacity of P. aeruginosa to form biofilms and resist antibiotics is closely correlated with quorum sensing (QS). Disrupting QS by QS inhibitors is a promising strategy for treating chronic infections. Here, we evaluated the effect of hordenine, a recently characterized QS inhibitor, on the susceptibility of aminoglycoside antibiotics against P. aeruginosa biofilms. Hordenine significantly enhanced the susceptibility of aminoglycoside antibiotics tobramycin, gentamycin, and amikacin against P. aeruginosa PAO1 biofilm formation. Combinations of hordenine and aminoglycoside antibiotics showed potent efficiency in disrupting the preformed biofilms of P. aeruginosa. Microscopic observations showed flat, scattered, and unstructured biofilm architecture after treatment with hordenine. Mechanistic study further revealed that hordenine treatment led to the downregulation of genes involved in QS and biofilm formation. Thus, our results suggest that hordenine has the potential to function as an antibiotic accelerant in treating P. aeruginosa infections.

is a ubiquitous pathogen that causes various infectious diseases through the regulation of quorum sensing (QS). The strategy of interfering with the QS systems of , coupled with a reduction in the dosage of conventional antibiotics, presents a potential solution to treating infection and mitigating antibiotic resistance. In this study, seven cinnamoyl hydroxamates were synthesized to evaluate their inhibitory effects on QS of . Among these cinnamic acid derivatives, we found cinnamoyl hydroxamic acid (CHA) and 3-methoxy-cinnamoyl hydroxamic acid (MCHA) were the two most effective candidates. Furtherly, the effect of CHA and MCHA on the production of virulence factors and biofilm of were evaluated. Ultimately, our study may offer promising potential for treating infections and reducing its virulence. The disc diffusion test were conducted to evaluate inhibitory effects on QS of seven cinnamoyl hydroxamates. The influence of CHA and MCHA on the production of virulence and flagellar motility of was furtherly explored. Scanning electron microscopy (SEM) experiment were conducted to evaluate the suppression of CHA and MCHA on the formed biofilm of . RT-qPCR was used to detect rhlI, lasA, lasB, rhlA, rhlB, and oprL genes in . docking study was performed to explore the molecular mechanism of CHA and MCHA. The synergistic effects of CHA with gentamicin were detected on biofilm cell dispersal. After treatment of CHA or MCHA, the production of multiple virulence factors, including pyocyanin, proteases, rhamnolipid, and siderophore, and swimming and swarming motilities in were inhibited significantly. And our results showed CHA and MCHA could eliminate the formed biofilm of . RT-qPCR revealed that CHA and MCHA inhibited the expression of QS related genes in . Molecular docking indicated that CHA and MCHA primarily inhibited the RhlI/R system in by competing with the cognate signaling molecule C4-HSL.Additionally, CHA exhibited potent synergistic effects with gentamicin on biofilm cell dispersal. is one of the most clinically and epidemiologically important bacteria and a primary cause of catheter-related urinary tract infections and ventilator-associated pneumonia. This study aims to explore whether cinnamoyl hydroxamates have inhibitory effects on QS. And our results indicate that CHA and MCHA, as two novel QSIs, offer promising potential for treating P. aeruginosa infections and reducing its virulence.

Siderophore is necessary for the survival of microorganisms and is interregulated with quorum sensing (QS) systems. It is related to growth, proliferation, virulence, and other bacterial social activities as a virulence factor. Thus, we speculated that the QS system could be occluded by inhibiting siderophore production. 2-Hydroxymethyl-1-methyl-5-nitroimidazole (HMMN), one siderophore inhibitor of Pseudomonas aeruginosa PAO1 ( P. aeruginosa PAO1), was obtained by using the Chromeazurol S (CAS) method. We found that HMMN inhibited siderophore production and influenced the biological effects of QS regulation, including biofilm formation and pyocyanin production. HMMN (150 μg/ml) inhibited the siderophore production of P. aeruginosa PAO1 by 69.37%. In addition, HMMN could inhibit pyocyanin production and biofilm formation and erase the formed biofilm of P. aeruginosa PAO1. HMMN (150 μg/ml) inhibited the biofilm formation of P. aeruginosa PAO1 by 28.24%. The erasure rate of the formed biofilm reached 17.03%. Furthermore, HMMN (150 μg/ml) inhibited P. aeruginosa PAO1 pyocyanin production by 36.06%. Meanwhile, positive-control hordenine (500.0 μg/ml) reduced the biofilm formation and pyocyanin production of P. aeruginosa PAO1 by 14.42% and 34.35%, respectively. The erasure rate of hordenine to the formed biofilm is 11.05% at 500 μg/ml. Quantitative real-time polymerase chain reaction (qRT-PCR) showed that HMMN downregulates not only siderophore-related genes but also QS-related genes, as well as hordenine. These results suggest that a siderophore inhibitor could be used as a QS inhibitor to occlude the QS system and reduce virulence.