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INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY · 2025 · IF 5.2

Synergistic inhibition of Pseudomonas aeruginosa by EGCG and I3A: preliminary mechanisms and application in fish meat preservation

Yongqi Tian,Yuanyuan Chen,Ruyang Huang,Tao Wang,Shaoyun Wang

Synergistic bacteriostatic action represents a potent strategy for combating microbial contamination in the food industry. This study investigated the synergistic bacteriostatic effect of epigallocatechin gallate (EGCG) and indole-3-carboxaldehyde (I3A). Results showed a pronounced synergistic action of EGCG and I3A against diverse food spoilage microorganisms, most notably Pseudomonas aeruginosa ( P. aeruginosa ), with a fractional inhibitory concentration index (FICI) of 0.25. Further research revealed that EGCG disrupted the cell wall and cell membrane of P. aeruginosa , while supplementing I3A significantly boosted the concentration of intracellular reactive oxygen species, thereby inflicting cellular damage. Moreover, the EGCG-I3A treatment inhibited the biofilm formation of P. aeruginosa in a dose-dependent manner, with the effectiveness increasing with the quantity of I3A added. Metabolomic study revealed a perturbation in glutathione and taurine metabolic pathways post synergistic treatment, compromising redox homeostasis. This synergistic treatment also downregulated uracil, proline, and glutamate metabolites, thereby suppressing Quorum Sensing (QS) and biofilm-associated expression within P. aeruginosa . Additionally, the combination significantly inhibited P. aeruginosa growth in fish meat. In essence, this study underscored the synergistic bacteriostatic efficacy of EGCG and I3A, highlighting its potential application in food preservation.

CAS / MDL: 487-89-8
研究领域: 食品科学 · 微生物学 · 生物化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Microbiology Spectrum · 2025 · IF 3.8

Regulatory roles of an sRNA derived from the 5´ UTR and sequence internal to lapA in Pseudomonas aeruginosa PAO1

Xiaojuan Tan,Jingjing Xiao,Qianqian Liu,Ting Yang,Dandan Feng,Ruyi Zheng,Liping Luo,Xi Cheng,Dongsheng Du,Minghui Li,Jinwei Zhou,Guoping Zhu

Several key virulence factors of Pseudomonas aeruginosa are regulated by quorum-sensing systems, small noncoding RNAs (sRNAs), and environmental stress, leading to a high mortality rate. Our previous studies indicated that the alkaline phosphatase LapA regulated P. aeruginosa PAO1 biofilm formation in a chronic wound model established with ex vivo porcine skin explants. Notably, one particular sRNA located upstream of the lapA gene was highly expressed in the model. Therefore, the sRNA was further characterized via northern blotting and rapid amplification of cDNA ends. The results revealed that the sRNA we named LapS is 197 nucleotides in length and is derived from the 5´ UTR and sequence internal to the lapA gene. Next, LapS mutation, overexpression, and complementation strains were constructed from the PAO1 strain, and phenotypic experiments associated with lapA were performed and compared with those of the ΔlapA and wild-type strains. The results indicated that LapS is involved in regulating swarming motility, rhamnolipid and alkaline phosphatase production, las/rhl quorum-sensing systems, and biofilm formation by controlling the level of lapA mRNA under phosphate-depleted conditions. Therefore, this LapS-lapA signaling cascade is beneficial for balancing the virulence regulation of P. aeruginosa. Additionally, an in vitro study indicated that LapS directly and post-transcriptionally regulated at least one unlinked gene, putA, which encodes bifunctional proline dehydrogenase, a virulence factor of P. aeruginosa. Collectively, our findings reveal a previously unstudied regulatory sRNA and advance the understanding of the roles of sRNAs in the pathogenicity of P. aeruginosa.

CAS / MDL: 168982-69-2 67605-85-0
研究领域: 微生物学 · 分子生物学 · 病原体研究
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Nature Communications · 2025 ·Vol. 16 ·期 1 ·1-19 · IF 15.7

CRISPRi screen identifies FprB as a synergistic target for gallium therapy in Pseudomonas aeruginosa

Zhang Yu,Zhang Tingting,Xiao Xue,Wang Yejun,Kawalek Adam,Ou Jinzhao,Ren Anmin,Sun Wenhao,de Bakker Vincent,Liu Yujie,Li Yuelong,Yang Liang,Ye Liang,Jia Ning,Veening Jan-Willem,Liu Xue

With the rise of antibiotic-resistant bacteria, non-antibiotic therapies like gallium gain increasing attention. Intravenous gallium nitrate is under Phase II clinical trials to treat chronic Pseudomonas aeruginosa infections in cystic fibrosis patients. However, its clinical efficacy is constrained by the achievable peak concentration in human tissue. To address this limitation, we apply a genome-wide CRISPR interference approach (CRISPRi-seq) to identify potential synergistic targets with gallium. We classify the essential genes by response time and growth reduction, pinpointing the most vulnerable therapeutic targets in this species. In addition, we identify a highly conserved gene, fprB , encoding a ferredoxin-NADP⁺ reductase, whose deletion sensitizes P. aeruginosa to gallium, lowering its MIC by 32-fold and shifting mode of action from bacteriostatic to bactericidal. Further investigation reveals that FprB plays a critical role in modulating oxidative stress induced by gallium, via control of iron homeostasis and reactive oxygen species accumulation. Deleting fprB enhances gallium’s efficacy against biofilm formation and improves outcomes in a murine lung infection model of P. aeruginosa , suggesting FprB is a promising drug target in combination with gallium. Overall, our data show CRISPRi-seq as a powerful tool for systematic genetic analysis of P. aeruginosa , advancing the identification of novel therapeutic targets.

CAS / MDL: 771-97-1
研究领域: 微生物学 · 分子生物学 · 药理学 · 基因组学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF CONTROLLED RELEASE · 2024 · IF 10.5

Tailored multilayer nanoparticles against resistant P. aeruginosa by disrupting the thickened mucus, dense biofilm and hyperinflammation

Mao Xu,Shihui Yu,Pengyu Li,Yili Chen,Yujun Chen,Jieyi Pan,Xin Deng,Haiyan Hu

Therapeutic challenges of chronic pulmonary infections caused by multidrug-resistant Pseudomonas aeruginosa (MDR P. aeruginosa ) biofilms due to significantly enhanced antibiotic resistance. This resistance is driven by reduced outer membrane permeability, biofilm barriers, and excessive secretion of virulence factors. Thickened mucus in the airways exacerbates the problem by impeding antibiotic penetration, providing a breeding ground for biofilms, consequently aggravating infection. Moreover, biofilms recruit numerous immune cells, resulting in chronic inflammation and lung tissue damage. In turn, damaged airway further facilitates bacterial colonization and elevated mucus production. To thoroughly disintegrate the stubborn triad of “thickened mucus & dense biofilm & excessive inflammation” and address drug resistance, tailored multilayer nanoparticles (NPVC/PBIP NPs) were developed. NPVC/PBIP NPs were engineered through self-assembly of vanillin-chitosan amphiphilic polymer loading polymyxin B-linoleic acid ion pairs in. Then polyaspartic acid and N -acetylcysteine-ε-poly- l -lysine were coated by layer-by-layer on the surface of vanillin-chitosan NPs via electrostatic interactions. As expected, the NAC units on NPVC/PBIP NPs effectively thinned human clinical sputum and porcine sputum, resulting in rapid sputum penetration followed by biofilm permeation. NPVC/PBIP NPs achieved over 99 % eradication of mature biofilms in vitro . Furthermore, they effectively inhibited virulence factors production and bacteria re-adhesion (biofilm reformation) while exhibiting superior anti-inflammatory and antioxidant activities. In a chronic pulmonary infection model, NPVC/PBIP NPs remarkably thinned airway mucus, reduced bacterial burden by 99.7 %, alleviated inflammatory cell infiltration, and minimized lung tissue damage. In summary, the NPVC/PBIP NPs represent a novel and promising strategy to manage MDR P. aeruginosa biofilms associated infections by disintegrating the stubborn triad of “thickened mucus & dense biofilm & excessive inflammation”.

研究领域: 医学 · 微生物学 · 药剂学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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APPLIED MICROBIOLOGY AND BIOTECHNOLOGY · 2018 ·Vol. 103 ·期 2 ·903-915 · IF 3.34

Chlorogenic acid attenuates virulence factors and pathogenicity of Pseudomonas aeruginosa by regulating quorum sensing

Wang Hong,Chu Weihua,Ye Chao,Gaeta Bruno,Tao Huimin,Wang Min,Qiu Zheng

Quorum sensing (QS) is a cell-to-cell communication that is used by bacteria to regulate collective behaviors. Quorum sensing controls virulence factor production in many bacterial species and it is regarded as an attractive target to combat bacterial pathogenicity, especially against antibiotic-resistant bacteria. Chlorogenic acid (CA), abundant in fruits, vegetables, and Chinese herbs, processes multiple activities. In this research, we explored its quorum sensing quenching activity. In Pseudomonas aeruginosa , CA significantly inhibited the formation of biofilm, the ability of swarming, and virulence factors including protease and elastase activities and rhamnolipid and pyocyanin production. CA showed similar inhibitory effects in Chromobacterium violaceum on its biofilm formation, swarming motility, chitinolytic activity and violacein production. We examined the expression of QS-related genes in  P.aeruginosa  and found these genes were all downregulated by CA treatment. Computational modeling revealed that CA can form hydrogen bonds with all three QS receptors. Caenorhabditis elegans and mouse infection models were employed to explore the anti-virulence ability of CA and its effect on pathogenesis process in vivo . CA extended the survival period and reduced the quantity of P. aeruginosa in nematode gut, showing a moderate protective effect on C. elegans . In mice wound model, CA-treated groups showed an accelerating healing rate and the bacteria number in wound area was also decreased by CA treatment. It is suggested by our research that CA has potential to be used as an anti-virulence factor in P. aeruginosa infection.

研究领域: 微生物学 · 药理学 · 感染病学
✓ 已验证 DOI PubMed 高影响因子
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SENSORS AND ACTUATORS B-CHEMICAL · 2020 · IF 7.1

Gelatin-based photonic hydrogels for visual detection of pathogenic Pseudomonas aeruginosa

Yujie Gao,Yu Chen,Miaomiao Li,Lizhen Jia,Lianbin Zhang,Jintao Zhu

Identification or detection of pathogenic microbes is one of the most important aspects to prevent and/or treat bacterial infection. In this study, we report a facile yet versatile strategy for preparation of gelatin-based photonic hydrogel sensors for visual detection of Pseudomonas aeruginosa ( P. aeruginosa ). The photonic hydrogels are generated by in-situ photopolymerization of acrylamide (AM), N , N ’-methylenebis-(acrylamide) (BIS), and gelatin methacrylate (GelMA) with the self-assembled one-dimensional (1D) chain-like structures of carbon-encapsulated Fe 3 O 4 nanoparticles (Fe 3 O 4 @C NPs). In the presence of P. aeruginosa , the hydrolysis of gelatin triggered by gelatinase reduces the crosslinking density of photonic hydrogel, expands the hydrogel in volume, increases the lattice spacing of the colloidal particles, and red-shifts the reflection spectra of the photonic hydrogel. The optical appearance variation of the photonic hydrogel, resulting from the reflection peak shift, can be observed by naked eyes. Besides, we show that the photonic hydrogels exhibit negligible appearance changes with the presence of Escherichia coli ( E. coli ), indicating their potential for distinguishing various bacteria by a simple structural color variation. This finding provides a proof-of-concept for a colorimetric sensor for visual detection of P. aeruginosa and demonstrates the great potential of the photonic hydrogels in visual detection of pathogens.

研究领域: 生物医学工程 · 微生物学 · 材料科学
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Food Science & Nutrition · 2021 ·Vol. 9 ·期 7 ·3873-3884 · IF 2.863

Rapid detection of Pseudomonas aeruginosa using a DNAzyme-based sensor

Mingcan Qin,Xiaoyi Ma,Shihui Fan,Hangjie Wu,Wanli Yan,Xiaopeng Tian,Jing Lu,Mingsheng Lyu,Shujun Wang

In the present study, a DNAzyme was screened in vitro through the use of a DNA library and crude extracellular mixture (CEM) of Pseudomonas aeruginosa . Following eight rounds of selection, a DNAzyme termed PAE-1 was obtained, which displayed high rates of cleavage with strong specificity. A fluorescent biosensor was designed for the detection of P. aeruginosa in combination with the DNAzyme. A detection limit as low as 1.2 cfu/ml was observed. Using proteases and filtration, it was determined that the target was a protein with a molecular weight of 10 kDa–50 kDa. The DNAzyme was combined with a polystyrene board to construct a simple indicator plate sensor which produced a color that identified the target within 10 min. The results were reliable when tap water and food samples were tested. The present study provides a novel experimental strategy for the development of sensors based on a DNAzyme to rapidly detect P. aeruginosa in the field.

研究领域: 分子生物学 · 微生物学 · 生物传感技术
✓ 已验证 DOI PubMed 高影响因子
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Biotechnology Journal · 2024 ·Vol. 19 ·期 2 ·2300542 · IF 3.2

Initial cyclic-di-GMP upregulation triggers sporadic cellular expansion leading to improved cellular survival

Yongshuai Yang,Siyu Guo,Can-Jian Hong,Zhao-Xun Liang,Chun Loong Ho

Bacterial second messenger c-di-GMP upregulation is associated with the transition from planktonic to sessile microbial lifestyle, inhibiting cellular motility, and virulence. However, in-depth elucidation of the cellular processes resulting from c-di-GMP upregulation has not been fully explored. Here, we report the role of upregulated cellular c-di-GMP in promoting planktonic cell growth of Escherichia coli K12 and Pseudomonas aeruginosa PAO1. We found a rapid expansion of cellular growth during initial cellular c-di-GMP upregulation, resulting in a larger planktonic bacterial population. The initial increase in c-di-GMP levels promotes bacterial swarming motility during the growth phase, which is subsequently inhibited by the continuous increase of c-di-GMP, and ultimately facilitates the formation of biofilms. We demonstrated that c-di-GMP upregulation triggers key bacterial genes linked to bacterial growth, swarming motility, and biofilm formation. These genes are mainly controlled by the master regulatory genes csgD and csrA . This study provides us a glimpse of the bacterial behavior of evading potential threats through adapting lifestyle changes via c-di-GMP regulation.

研究领域: 微生物学 · 分子生物学
✓ 已验证 DOI PubMed 高影响因子
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Biofilm · 2024 · IF 5.9

Dopamine, an exogenous quorum sensing signaling molecule or a modulating factor in Pseudomonas aeruginosa?

Shi-Liang Xiang,Kai-Zhong Xu,Lu-Jun Yin,Yong Rao,Bo Wang,Ai-Qun Jia

Pseudomonas aeruginosa is recognized globally as an opportunistic pathogen of considerable concern due to its high virulence and pathogenicity, especially in immunocompromised individuals. While research has identified several endogenous quorum sensing (QS) signaling molecules that enhance the virulence and pathogenicity of P. aeruginosa , investigations on exogenous QS signaling molecules or modulating factors remain limited. This study found that dopamine serves as an exogenous QS signaling molecule or modulating factor of P. aeruginosa PAO1, enhancing the production of virulence factors and biofilms. Compared to the control group, treatment with 40 μM dopamine resulted in a 33.1 % increase in biofilm formation, 68.1 % increase in swimming mobility, 63.1 % increase in swarming mobility, 147.2 % increase in the signaling molecule 3-oxo-C12-HSL, and 50.5 %, 28.5 %, 27.0 %, and 33.2 % increases in the virulence factors alginate, rhamnolipids, protease, and pyocyanin, respectively. This study further explored the mechanism of dopamine regulating the biofilm formation and virulence of P. aeruginosa PAO1 through transcriptome and metabolome. Transcriptomic analysis showed that dopamine promoted the expression of virulence genes psl, alg, lasA, rhlABC , rml , and phz in P. aeruginosa PAO1. Metabolomic analysis revealed changes in the concentrations of tryptophan, pyruvate, ethanolamine, glycine, 3-hydroxybutyric acid, and alizarin. Furthermore, KEGG enrichment analysis of altered genes and metabolites indicated that dopamine enhanced phenylalanine, tyrosine, and tryptophan in P. aeruginosa PAO1. The results of this study will contribute to the development of novel exogenous QS signaling molecules or modulating factors and advance our understanding of the interactions between P. aeruginosa and the host environment.

CAS / MDL: 62-31-7
研究领域: 微生物学 · 分子生物学 · 感染与免疫
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Frontiers in Microbiology · 2024 · IF 4

pH-mediated potentiation of gallium nitrate against Pseudomonas aeruginosa

Liu Chang,Cui Chenxuan,Tan Xiaoxin,Miao Junjie,Wang Wei,Ren Han,Wu Hua,Zheng Cuiying,Ren Huan,Kang Weijun

The emergence of multidrug-resistant Pseudomonas aeruginosa isolates is a growing concern for public health, necessitating new therapeutic strategies. Gallium nitrate [Ga(NO3)3], a medication for cancer-related hypercalcemia, has attracted great attention due to its ability to inhibit P. aeruginosa growth and biofilm formation by disrupting iron metabolism. However, the antibacterial efficacy of Ga(NO3)3 is not always satisfactory. It is imperative to investigate the factors that affect the bactericidal effects of Ga(NO3)3 and to identify new ways to enhance its efficacy. This study focused on the impact of pH on P. aeruginosa resistance to Ga(NO3)3, along with the underlying mechanism. The results indicate that acidic conditions could increase the effectiveness of Ga(NO3)3 against P. aeruginosa by promoting the production of pyochelin and gallium uptake. Subsequently, using glutamic acid, a clinically compatible acidic amino acid, the pH was significantly lowered and enhanced the bactericidal and inhibitory efficacy of Ga(NO3)3 against biofilm formation by P. aeruginosa, including a reference strain PA14 and several multidrug-resistant clinical isolates. Furthermore, we used an abscess mouse model to evaluate this combination in vivo; the results show that the combination of glutamic acid and Ga(NO3)3 significantly improved P. aeruginosa clearance. Overall, the present study demonstrates that acidic conditions can increase the sensitivity of P. aeruginosa to Ga(NO3)3. Combining glutamic acid and Ga(NO3)3 is a potential strategy for the treatment of P. aeruginosa infections.

CAS / MDL: 6461-04-7
研究领域: 微生物学 · 感染与免疫 · 药理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ENVIRONMENTAL POLLUTION · 2020 · IF 6.793

Bioreduction of hexavalent chromium on goethite in the presence of Pseudomonas aeruginosa

Yihao Li,Huimin Wang,Pingxiao Wu,Langfeng Yu,Saeed Rehman,Junfeng Wang,Shanshan Yang,Nengwu Zhu

The effective mineral absorption and bioreduction were considered as two preferred processes to alleviate the bioavailability and toxicity of toxic trace metals. In this study, the bioreduction of hexavalent chromium (Cr(VI)) on goethite (FeOOH) in the presence of Pseudomonas aeruginosa ( P. aeruginosa ) was investigated with different environmental factors, including carbon source concentrations, pH, temperature and initial Cr(VI) concentrations. The characterization of FeOOH– P. aeruginosa indicated that P. aeruginosa was surrounded by FeOOH, which could provide the essential iron for bacterial growth and reduce Cr(VI) to Cr(III). The optimal experimental conditions for Cr(VI) (initial concentration: 35 mg L −1 ) absorption (∼46%) and bioreduction (∼54%) involved a temperature of 45 °C and pH of 5.5. Meanwhile, extracellular polymeric substances (EPS) secreted by P. aeruginosa and its functional groups played important roles in the reduction of Cr(VI). They could reduce Cr(VI) to Cr(III) and transform to Cr(OH) 3 or Fe x -Cr (1-x) (OH) 3 precipitation. These results of this study are of significant importance to better understand the environmental geochemical behavior of Cr(VI) with the interactions between soil minerals and microorganisms .

CAS / MDL: 7778-50-9
研究领域: 环境科学 · 微生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Frontiers in Microbiology · 2023 · IF 5.2

Geraniol attenuates virulence factors by inhibiting quorum sensing of Pseudomonas aeruginosa

Li Wen-Ru,Zeng Tao-Hua,Zhang Zhi-Qing,Shi Qing-Shan,Xie Xiao-Bao

Pseudomonas aeruginosa is a ubiquitous opportunistic pathogen that can cause severe respiratory tract infections. Geraniol, a chemical component of essential oils, has antimicrobial and anti-inflammatory activities, along with low toxicity. However, the effect and mechanism of geraniol against P. aeruginosa virulence factors are rarely studied. In this study, we investigated the quorum sensing (QS) inhibitory effects and mechanisms of geraniol against P. aeruginosa PAO1, using physiological and biochemical techniques, quantitative reverse transcription polymerase chain reaction, and transcriptomics. Geraniol slightly affected P. aeruginosa PAO1 growth, prolonged the lag phase, and delayed growth periods in a concentration-dependent manner. Geraniol inhibited three QS systems of P. aeruginosa, las, rhl, and pqs by suppressing the expression level of their key genes, including the three signal synthetase encoding genes of lasI, rhlI, and pqsABCDEH, and the corresponding signal receptor encoding genes of lasR, rhlR, and pqsR. Geraniol also suppressed certain virulence genes regulated by these three QS systems, including rhlABC, lasAB, lecAB, phzABMS, and pelABG, resulting in the attenuation of the related virulence factors, rhamnolipids, exoprotease LasA, elastase, lectin, pyocyanin, and biofilm. In conclusion, geraniol can suppress the virulence factors of P. aeruginosa PAO1 by inhibiting the three QS systems of las, rhl, and pqs. This study is significant for improving the treatment of bacterial infections caused by P. aeruginosa.

CAS / MDL: 106-24-1
研究领域: 微生物学 · 药理学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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