A Cyclic Disulfide Diastereomer From Bioactive Fraction of Bruguiera gymnorhiza Shows Anti–Pseudomonas aeruginosa Activity

Abstract

Pseudomonas aeruginosa is an opportunistic pathogen that commonly causes hospital-acquired infection and is of great concern in immunocompromised patients. The quorum sensing (QS) mechanism of P. aeruginosa is well studied and known to be responsible for pathogenicity and virulence. The QS inhibitor derived from the natural product can be an important therapeutic agent for pathogen control. The present study reports the role of Bruguiera gymnorhiza purified fraction (BG138) in inhibiting virulence factor production, biofilm formation, quorum sensing molecules, and expression of QS-related genes of P. aeruginosa. Structural characterization of BG138 by high resolution mass spectrometry, Fourier transform infrared spectroscopy, 1D (1H and 13C NMR) and 2D NMR reveals that the fraction is a mixture of already known cyclic disulfide diastereomer, namely, brugierol and isobrugierol. The minimum inhibitory concentration (MIC) of BG138 against P. aeruginosa was 32 μg/ml. Biofilm formation was significantly reduced at sub-MIC concentrations of BG138. Scanning electron microscopy analysis reports the concentration-dependent biofilm inhibition and morphological changes of P. aeruginosa. Flow cytometry–based cell viability assay showed that P. aeruginosa cells exhibit increased propidium iodide uptake on treatment with 32 and 64 μg/ml of BG138. At sub-MIC concentrations, BG138 exhibited significant inhibition of virulence factors and reduced swimming and swarming motility of P. aeruginosa. Furthermore, the effect of BG138 on the expression of QS-related genes was investigated by qRT-PCR. Taken together, our study reports the isolation and structural characterization of bioactive fraction BG138 from B. gymnorhiza and its anti-biofilm, anti-virulence, anti-quorum sensing, and cell-damaging activities against P. aeruginosa.

1H-Pyrrole-2,5-dicarboxylic acid, a quorum sensing inhibitor from one endophytic fungus in Areca catechu L., acts as antibiotic accelerant against Pseudomonas aeruginosa

“…The results indicated that PT22 may impede acylated homoserine lactone (AHL) production, resulting in QSI activity, and presents higher activity in reducing C4-HSL production. The endophytic fungus Bruguiera gymnorhiza purified fraction (BG138) interferes with the P. aeruginosa QS system, resulting in a decrease in QS signaling molecules and transcriptional levels of the QS-related genes ( Dahibhate et al., 2022 ). Similar results were found in which citrinin could downregulate the QS-related genes ( las I, las R, rhl I, and rhl R) and showed a QSI activity of P. aeruginosa ( Ji et al., 2023 ).…”

“…The growth curves measurement assays were performed according to the reported methods with some modifications ( Dahibhate et al., 2022 ). Overnight cultures of P. aeruginosa PAO1 were inoculated into 5 mL fresh LB broth with 0.1% volume percent and supplemented with different concentrations of PT22 (0.50 mg/mL, 0.75 mg/mL, 1.00 mg/mL, and 2.00 mg/mL).…”

Chemical Constituents and Biological Activities of Bruguiera Genus and Its Endophytes: A Review

“…The diversity of diterpenoids in plants playing important roles in plant development, stress resistance, and interactions with environmental microorganisms, depends on the various skeletons biosynthesized by terpene synthases and the substrate promiscuity of cytochrome P450 monooxygenases (P450s), along with other postmodification enzymes [38]. In the genus Bruguiera, researchers have isolated five different skeletal types of diterpenoid (Table 2 and Figure 3), namely ent-pimarane (79-82), isopi-marane (83)(84), ent-beyerane (85-86), ent-kaurane (62)(63)(64)(65)(66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76)(77)(78), and ent-gibberellane (59-61), with the key intermediate pimarane in their biosynthesis. Most sesterpenoids are sourced from marine organisms, with approximately 15% of these compounds having been isolated from plants [44].…”

“…Previous research indicates that sulfides play a crucial role in plant defense against various pathogens and pests [73]. Dahibhate et al [74] discovered that a mixture of brugierol and isobrugierol exhibited inhibitory activity against Pseudomonas aeruginosa by reducing the formation of virulence biofilms controlled by the quorum sensing system, lowering the level of virulence factors, thereby attenuating the pathogenicity of the bacterium against Bruguiera plants. Simultaneously, Zhang et al [21,75] cultured and isolated the endophytic fungus C. cladosporioides MA-299 from the leaves of B. gymnorrhiza, obtaining seven sulfur-containing 12-membered macrocyclic lactones (179)(180)(181)(182)(183)(184)(185).…”