Paeonol Interferes With Quorum-Sensing in Pseudomonas aeruginosa and Modulates Inflammatory Responses In Vitro and In Vivo

Tang, Huaqiao; Yang, Dan; Zhu, Ling; Shi, Fei; Ye, Gang; Guo, Hongrui; Deng, Huidan; Zhao, Ling; Xu, Zhiwen; Li, Yinglun

doi:10.3389/fimmu.2022.896874

Cited by 14 publications

(14 citation statements)

References 58 publications

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“…The present study showed that the level of serum LPS was increased and positively correlated with the abundance of Pseudomonas aeruginosa in GAD patients. Previous studies also reported that Pseudomonas aeruginosa induces macrophages to release various proinflammatory cytokines and chemokines through activation of the TLR4/MyD88/NF-κB signaling pathway ( 49 , 50 ). Our results provide evidence for the association between systemic inflammatory response and ear canal dysbiosis.…”

Section: Discussionmentioning

confidence: 89%

Microbiota-ear-brain interaction is associated with generalized anxiety disorder through activation of inflammatory cytokine responses

Feng

Zhu²,

Li³

et al. 2023

Front. Immunol.

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IntroductionGeneralized anxiety disorder (GAD) is one of the most enduring anxiety disorders, being associated with increased systemic inflammation. However, the trigger and mechanisms underlying the activation of inflammatory cytokine responses in GAD remain poorly understood.Materials and methodsWe characterized the ear canal microbiome in GAD patients through 16S rRNA gene sequencing and metagenomic sequencing and identified the serum inflammatory markers in GAD patients. Spearman correlations were applied to test the relationship between the microbiota changes and systemic inflammation.ResultsOur findings showed the higher microbial diversity, accompanied with the significantly increased abundance of Proteobacteria, and decreased abundance of Firmicutes in the ear canal of GAD participants compared to that of the age- and sex-matched healthy controls (HC). Metagenomic sequencing showed that Pseudomonas aeruginosa were significantly increased at species-level in GAD patients. Furthermore, we observed the relative abundance of Pseudomonas aeruginosa was positively associated with elevated systemic inflammatory markers and the severity of disease, suggesting that these ear canal microbiota alterations might be correlated with GAD by activating the inflammatory response.ConclusionsThese findings indicate that microbiota-ear-brain interaction via upregulating inflammatory reaction involve in the development of GAD, as well as suggest that ear canal bacterial communities may be a target for therapeutic intervention.

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Section: Discussionmentioning

confidence: 89%

Microbiota-ear-brain interaction is associated with generalized anxiety disorder through activation of inflammatory cytokine responses

Feng

Zhu²,

Li³

et al. 2023

Front. Immunol.

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“…It has been demonstrated to exert a wide range of activities, spanning from immune regulatory activity [88], anti-inflammatory [89], to antibacterial effect [90,91]. Paeonol efficiently reduces infection of macrophages by P. aeruginosa, as described recently [92]. Furthermore, it has the potential to drastically impede the expression of QS-regulated gene rhlI/R and pqsA/R [93].…”

Section: Natural Molecules Reducing Pseudomonas Aeruginosa Growthmentioning

confidence: 89%

“…1 Paeonol effects on Pseudomonas aeruginosa infected macrophages. Based on the work of Tang H et al (2022) [ 92 ]. Pathogen bacteria and their genes are in yellow, macrophage is in blue and the components of immune system in other colours …”

Section: Main Textmentioning

confidence: 99%

Recent advances in therapeutic targets identification and development of treatment strategies towards Pseudomonas aeruginosa infections

et al. 2023

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The opportunistic human pathogen Pseudomonas aeruginosa is the causal agent of a wide variety of infections. This non-fermentative Gram-negative bacillus can colonize zones where the skin barrier is weakened, such as wounds or burns. It also causes infections of the urinary tract, respiratory system or bloodstream. P. aeruginosa infections are common in hospitalized patients for which multidrug-resistant, respectively extensively drug-resistant isolates can be a strong contributor to a high rate of in-hospital mortality. Moreover, chronic respiratory system infections of cystic fibrosis patients are especially concerning, since very tedious to treat. P. aeruginosa exploits diverse cell-associated and secreted virulence factors, which play essential roles in its pathogenesis. Those factors encompass carbohydrate-binding proteins, quorum sensing that monitor the production of extracellular products, genes conferring extensive drug resistance, and a secretion system to deliver effectors to kill competitors or subvert host essential functions. In this article, we highlight recent advances in the understanding of P. aeruginosa pathogenicity and virulence as well as efforts for the identification of new drug targets and the development of new therapeutic strategies against P. aeruginosa infections. These recent advances provide innovative and promising strategies to circumvent infection caused by this important human pathogen.

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“…Quantitative gene expression analysis was carried out on CFX Connect™ Real-Time PCR Detection System (Bio-Rad Laboratories, Segrate, Italy), using SYBR ® Select Master Mix for CFX (Life Technologies, Carlsbad, CA, USA) and ubiquitin for normalization. The primers used for real-time PCR analysis are reported in Table 2 [ 78 , 80 , 99 , 100 ].…”

Section: Methodsmentioning

confidence: 99%

Spiramycin Disarms Pseudomonas aeruginosa without Inhibiting Growth

et al. 2023

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Spiramycin is a 16-membered macrolide antibiotic currently used in therapy to treat infections caused by Gram-positive bacteria responsible for respiratory tract infections, and it is also effective against some Gram-negative bacteria and against Toxoplasma spp. In contrast, Pseudomonas aeruginosa, which is one of the pathogens of most concern globally, is intrinsically resistant to spiramycin. In this study we show that spiramycin inhibits the expression of virulence determinants in P. aeruginosa in the absence of any significant effect on bacterial multiplication. In vitro experiments demonstrated that production of pyoverdine and pyocyanin by an environmental strain of P. aeruginosa was markedly reduced in the presence of spiramycin, as were biofilm formation, swarming motility, and rhamnolipid production. Moreover, treatment of P. aeruginosa with spiramycin sensitized the bacterium to H2O2 exposure. The ability of spiramycin to dampen the virulence of the P. aeruginosa strain was confirmed in a Galleria mellonella animal model. The results demonstrated that when G. mellonella larvae were infected with P. aeruginosa, the mortality after 24 h was >90%. In contrast, when the spiramycin was injected together with the bacterium, the mortality dropped to about 50%. Furthermore, marked reduction in transcript levels of the antimicrobial peptides gallerimycin, gloverin and moricin, and lysozyme was found in G. mellonella larvae infected with P. aeruginosa and treated with spiramycin, compared to the larvae infected without spiramycin treatment suggesting an immunomodulatory activity of spiramycin. These results lay the foundation for clinical studies to investigate the possibility of using the spiramycin as an anti-virulence and anti-inflammatory drug for a more effective treatment of P. aeruginosa infections, in combination with other antibiotics.

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Paeonol Interferes With Quorum-Sensing in Pseudomonas aeruginosa and Modulates Inflammatory Responses In Vitro and In Vivo

Cited by 14 publications

References 58 publications

Microbiota-ear-brain interaction is associated with generalized anxiety disorder through activation of inflammatory cytokine responses

Microbiota-ear-brain interaction is associated with generalized anxiety disorder through activation of inflammatory cytokine responses

Recent advances in therapeutic targets identification and development of treatment strategies towards Pseudomonas aeruginosa infections

Spiramycin Disarms Pseudomonas aeruginosa without Inhibiting Growth

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