Inhibitory effect of norharmane on Serratia marcescens NJ01 quorum sensing-mediated virulence factors and biofilm formation.

Serratia marcescens NJ01, a Gram-negative bacterium, can infect tomato leaves and cause chlorosis and wilting. The present study evaluated the quorum sensing (QS) and biofilm inhibitory effects of seven carboline compounds against S. marcescens NJ01 at 20 µg ml-1, and subsequently focused the study on norharmane as this had the best inhibitory activity. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis confirmed the down-regulation of QS and biofilm related genes bsmA, bsmB, fimA, fimC, flhD, pigA, pigC and shlA on exposure to norharmane. Fourier-Transform Infrared Spectroscopy (FT-IR) analysis showed a reduction in the major components of the exopolysaccharide (EPS) matrix such as nucleic acids, proteins and fatty acids, which are involved in forming the tertiary structure of biofilms. Norharmane exposure also enhanced the susceptibility of the biofilm to ofloxacin. Hence, norharmane has the potential for use as an antibiotic adjuvant to enhance the efficacy of conventional antibiotics to reduce pathogenic bacterial infections.

Growth inhibition and metabolomic analysis of Xanthomonas oryzae pv. oryzae treated with resveratrol.

BACKGROUND: Xanthomonas oryzae pv. oryzae (Xoo) can cause destructive bacterial blight in rice. As an antibacterial, resveratrol may inhibit Xoo growth. This study focused on the potential structural-activity relationship of resveratrol and its derivatives against Xoo growth, and 1H-NMR-based metabolomic analysis was applied to investigate the global metabolite changes in Xoo after resveratrol treatment. RESULTS: Resveratrol showed the strongest inhibitory effects on Xoo growth compared with its derivatives, which lacked double bonds (compounds 4-6) or hydroxyls were substituted with methoxyls (compounds 7-9). The IC50 of resveratrol against Xoo growth was 11.67 ± 0.58 µg/mL. Results indicated that the double bond of resveratrol contributed to its inhibitory effects on Xoo growth, and hydroxyls were vital for this inhibition. Interestingly, resveratrol also significantly inhibited Xoo flagellum growth. Based on 1H-NMR global metabolic analysis, a total of 30 Xoo metabolites were identified, the changes in the metabolic profile indicated that resveratrol could cause oxidative stress as well as disturb energy, purine, amino acid, and NAD+ metabolism in Xoo, resulting in the observed inhibitory effects on growth. CONCLUSIONS: This study showed that the double bond of resveratrol contributed to its inhibitory effects on Xoo growth, and hydroxyls were also the important active groups. Resveratrol could cause oxidative stress of Xoo cells, and disturb the metabolism of energy, purine, amino acid and NAD +, thus inhibit Xoo growth.

Quorum sensing inhibition and tobramycin acceleration in Chromobacterium violaceum by two natural cinnamic acid derivatives.

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.

New Sesquiterpenoids From Plant-Associated Irpex lacteus.

Bacteria produce a large number of virulence factors through the quorum sensing (QS) mechanism. Inhibiting such QS system of the pathogens without disturbing their growth is a potential strategy to control multi-drug-resistant pathogens. To accomplish this, two new tremulane-type sesquiterpenoids, irpexolaceus H (1) and I (2), along with two known furan compounds, irpexlacte B (3) and C (4), were isolated from Orychophragmus violaceus (L.) OE Schulz endophytic fungus Irpex lacteus (Fr.) Fr. Their structures were elucidated by detailed spectroscopic data (NMR, HRESIMS, IR, and UV), single-crystal X-ray diffraction, and electronic circular dichroism (ECD) analysis. Furthermore, those compounds were evaluated for anti-quorum sensing (anti-QS) activity, and compound 3 was found contributing to the potential QS inhibitory activity.

Corrigendum: New Sesquiterpenoids From Plant-Associated Irpex lacteus.

[This corrects the article DOI: 10.3389/fchem.2022.905108.].

Sesquiterpenoids and furan derivatives from the Orychophragmus violaceus (L.) O.E. Schulz endophytic fungus Irpex lacteus OV38.

Nine undescribed compounds, including six tremulane-type sesquiterpenoids, irpexolaceus A-F, one phenolic bisabolane-type sesquiterpenoid, irpexolaceus G, and two furan derivatives, irpexonjust A-B, as well as eight known analogs, were isolated from an endophytic fungus (Irpex lacteus OV38) of Orychophragmus violaceus (L.) O.E. Schulz, a Chinese medicinal and edible plant. The structures of these natural compounds were elucidated based on NMR, HRESIMS, single-crystal X-ray diffraction, and ECD spectroscopic data. Among the tested isolates (50 µg/mL), the inhibitory effects of irpexolaceus A, C, D, F, and G, irpexonjust B, and irpexlacte B against NO release from LPS-induced RAW 264.7 cells were higher than 45%, while irpexlacte C (42.6%), irpexolaceus B (39.6%), irpexonjust A (43.7%), and irpexolaceus E (33.6%) exhibited weaker inhibitory effects on the release of NO.

Inhibition of Quorum Sensing and Virulence in Serratia marcescens by Hordenine.

Serratia marcescens NJ01 is a pathogenic bacterium isolated from diseased tomato leaves. Here, we report on the development of a tomato- S. marcescens host-pathogen system as a model to evaluate the effects of hordenine on quorum sensing (QS)-mediated pathogenicity under native conditions. Exposure to hordenine at 25, 50, and 100 µg/mL significantly inhibited the production of acyl-homoserine lactones and the formation of biofilms. Hordenine treatment notably enhanced the susceptibility of the preformed biofilms to ciprofloxacin by reducing the production of extracellular polysaccharides, destroying the architecture of biofilms, and changing the permeability of membranes, as evidenced by the scattered appearance and dominant red fluorescence in the combination-treated biofilms. Furthermore, the addition of hordenine affected the production of virulence factors, influenced the intracellular metabolites, and downregulated the expressions of QS- and biofilm-related genes. The plant infection model indicated that hordenine could significantly attenuate the pathogenicity of S. marcescens NJ01 in tomato plants. Thus, hordenine could act as a potential pesticide or pesticide accelerant in treating crop infections.

Hordenine: A Novel Quorum Sensing Inhibitor and Antibiofilm Agent against Pseudomonas aeruginosa.

The quorum sensing (QS) inhibitory activity of hordenine from sprouting barley against foodborne pathogen Pseudomonas aeruginosa was evaluated for the first time here. At concentrations ranging from 0.5 to 1.0 mg mL-1, hordenine inhibited the levels of acyl-homoserine lactones. The enhanced susceptibility of hordenine with netilmicin on P. aeruginosa PAO1 biofilm formation as well as their efficiency in disrupting preformed biofilms was also evaluated using scanning electron microscopy and confocal laser scanning microscopy (CLSM). Hordenine treatment inhibited the production of QS-related extracellular virulence factors of P. aeruginosa PAO1. Additionally, quantitative real-time polymerase chain reaction analysis demonstrated that the expressions of QS-related genes, lasI, lasR, rhlI, and rhlR, were significantly suppressed. Our results indicated that hordenine can serve as a competitive inhibitor for signaling molecules and act as a novel QS-based agent to defend against foodborne pathogens.