Microbial pathogenesis最新文献

{"title":"Effect of novel non-coding small RNA111 of Pseudomonas aeruginosa on bacterial virulence","authors":"Fanghong Wang ,&nbsp;Qiwei Li ,&nbsp;Song Li ,&nbsp;Peng Zhou ,&nbsp;Peng Ma ,&nbsp;Lan Wang ,&nbsp;Yaqin Liu ,&nbsp;Zhongzhong Guo ,&nbsp;Hongwei Liu ,&nbsp;Youqiang Li ,&nbsp;Weiguo Yin ,&nbsp;Juanjuan Han","doi":"10.1016/j.micpath.2024.107077","DOIUrl":"10.1016/j.micpath.2024.107077","url":null,"abstract":"<div><div><em>Pseudomonas aeruginosa</em> is an important gram-negative pathogen that often causes skin, respiratory, and bloodstream infections. The virulence of <em>P. aeruginosa</em> is regulated by sRNAs through a complex network, which is still incompletely understood. This study employed transcriptome sequencing (RNA-Seq) to screen sRNA 111, and real-time quantitative PCR was conducted for validation. In addition, an overexpression strain of sRNA111 was constructed and the effects of overexpression of sRNA111 on virulence factors such as biofilm formation, pyocyanin, swarming motility, inflammatory factors, and biofilm-associated factors were analyzed. The results revealed that sRNA111 might be closely related to the formation of <em>P. aeruginosa</em> biofilm. Compared to the vector, sRNA111 was found to enhance <em>P. aeruginosa</em> biofilm formation while also suppressing swarming motility, invasive ability, and adhesion capability. Meanwhile, sRNA111 up-regulated the expression of biofilm-related genes, such as Anr, pel family, polB, recA, etc., more significantly in the biofilm environment compared with the wild strain. In addition, sRNA111 effectively promoted the expression of inflammatory factors in the biofilm environment compared with the planktonic environment. These results implied that sRNA111 regulates the formation of <em>P. aeruginosa</em> biofilm and other virulence factors and further modulates the process of infection immunity.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"197 ","pages":"Article 107077"},"PeriodicalIF":3.3,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic defense: Quercetin and chondroitin sulfate combat bacterial trigger of rheumatoid arthritis, Proteus mirabilis through in-vitro and in-vivo mechanisms","authors":"P. Snega Priya ,&nbsp;Raghul Murugan ,&nbsp;R. Srileka ,&nbsp;S.P. Ramya Ranjan Nayak ,&nbsp;Thirumal Margesan ,&nbsp;Rajakrishnan Rajagopal ,&nbsp;Mukesh Pasupuleti ,&nbsp;Kathiravan Muthu Kumarodoss ,&nbsp;Jesu Arockiaraj","doi":"10.1016/j.micpath.2024.107086","DOIUrl":"10.1016/j.micpath.2024.107086","url":null,"abstract":"<div><div>Rheumatoid arthritis, a chronic autoimmune disorder characterized by joint inflammation, is thought to be exacerbated by bacterial infections, notably <em>Proteus mirabilis</em>. This study explores the combined effects of quercetin, a potent antioxidant and anti-inflammatory flavonoid, and chondroitin sulfate, known for its cartilage-protective properties, as a potential therapeutic approach. Molecular docking analyses revealed favourable interactions between these compounds and key pro-inflammatory cytokines IL-6 and TNF-α, suggesting their potential to disrupt inflammation-related signaling pathways. In vitro assays demonstrated that the quercetin-chondroitin sulfate combination (1:1 ratio) significantly inhibited oxidative stress and hemolysis, highlighting its enhanced anti-inflammatory and membrane-protective effects. The free radical scavenging assays further confirmed the antioxidant potential of this combination, which demonstrated strong radical scavenging activity. Antimicrobial assays showed notable antibacterial effects, with an increased inhibition zone against <em>P. mirabilis</em> when quercetin and chondroitin sulfate were combined, suggesting a synergistic antimicrobial action. In vivo, zebrafish subjected to bacterial stress showed improved survival rates with the quercetin and chondroitin sulfate combination treatment, along with enhanced mineralization and significant modulation of alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) activities, indicating its protective role in maintaining joint health. Furthermore, gene expression analysis revealed a substantial reduction in pro-inflammatory markers, including TNF-α and IL-6, demonstrating the quercetin and chondroitin sulfate combination's ability to mitigate inflammation. Together, these findings suggest that the quercetin and chondroitin sulfate combination hold significant therapeutic potential in reducing oxidative stress, inflammation, and microbial-induced RA exacerbations.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"197 ","pages":"Article 107086"},"PeriodicalIF":3.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting PI3Kγ Pathway for Treating Dengue virus Infection","authors":"Felipe R. da S. Santos ,&nbsp;Deborah F. Valadão ,&nbsp;Jordana L. Bambirra ,&nbsp;Thaiane P. Moreira ,&nbsp;Carla D.F. de Sousa ,&nbsp;Ingredy B.S. Passos ,&nbsp;Celso M. Queiroz-Junior ,&nbsp;Caio T. Fagundes ,&nbsp;Mauro M. Teixeira ,&nbsp;Vivian V. Costa ,&nbsp;Daniele G. Souza","doi":"10.1016/j.micpath.2024.107060","DOIUrl":"10.1016/j.micpath.2024.107060","url":null,"abstract":"<div><div>Dengue disease is a major problem worldwide, impacting millions of people annually with no specific approved treatments. The pathogenesis of dengue is a complex interplay of viral and host factors, driven in particular by an excessive inflammatory response triggered by the infection. While it has been observed that various viruses can modulate the PI3K/Akt signaling pathway to aid replication and theunderlying mechanisms remainunclear. The study aims to explore the impact of PI3Kγ inhibition during Dengue virus (DENV) infection <em>in vivo</em>. Experiments were performed using both wild-type (WT) and PI3Kγ knockout mice inoculated with DENV. Parameters, including survival rates, hematologic, virologic, histopathologic, and inflammatory analyzes, were evaluated. Additionally, the therapeutic potential of a selective PI3Kγ inhibitor (AS605240) was investigated in DENV-infected A129 mice. PI3Kγ deficiency resulted in lower lethality and provided protection against DENV-induced thrombocytopenia, decreased hemoconcentration, vascular permeability, and liver damage compared to DENV-infected WT littermates. In addition, PI3Kγ deficiency correlated with reduced viral replication in the blood, spleen and liver alongside decreased production of inflammatory mediators in plasma and spleen. Pharmacologic inhibition of PI3Kγ not only ameliorated DENV-induced thrombocytopenia and liver injury, but also reduced DENV replication in target organs. Treatment with AS605240 reduced the concentration of IL-6 in the spleen and plasma.This study sheds light on the significant pro-viral effects of the PI3Kγ signaling pathway during DENV infection and its central role in pathogenesis by curbing excessive DENV-induced inflammation. Inhibition of PI3Kγ shows promising host-directed target for developing novel Dengue disease therapies, offering substantial benefits to hosts.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"197 ","pages":"Article 107060"},"PeriodicalIF":3.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142554407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A whole genome sequencing-based assay to investigate antibiotic susceptibility and strain lineage of Helicobacter pylori","authors":"Yue Tong ,&nbsp;Ruoyu Dang ,&nbsp;Yongmei Yin ,&nbsp;Changjun Men ,&nbsp;Rimo Xi","doi":"10.1016/j.micpath.2024.107069","DOIUrl":"10.1016/j.micpath.2024.107069","url":null,"abstract":"<div><div><em>Helicobacter pylori</em> (<em>H. pylori</em>) antibiotic resistance has been widespread and increasing worldwide, which presented a significant challenge to the successful eradication of <em>H. pylori</em> infection. Identification of antibiotic resistance and exploration of potential resistance mechanisms are thus necessary for effective treatment. For this purpose, we herein develop a whole genome sequencing (WGS) assay based on next-generation sequencing (NGS) to detect the entire genome of 73 <em>H. pylori</em> strains isolated from gastric mucosa of patients in Tianjin, China, and analyzed the association between single-nucleotide polymorphism (SNP) in resistance-related genes and phenotypic sensitivity. We discovered the consistent relationship between genotypic and phenotypic resistance by A2143 C/G in <em>23S rRNA</em> for clarithromycin (Kappa: 0.882), N87 K/I in <em>gyrA</em> for levofloxacin (Kappa: 0.883), and wild-type of <em>pbp1</em> for amoxicillin. In addition, we obtained 4 super-resistant clinical strains of <em>H. pylori</em>, which formed thick, sticky biofilms, were extremely resistant to all antibiotics regardless of the present of mutations in antibiotic targets sites. Therefore, biofilm formation is also a mechanism of drug resistance, and biofilm-related proteins or genes are also expected to be used as screening markers for H. pylori resistance.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"197 ","pages":"Article 107069"},"PeriodicalIF":3.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142539345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-bacteria, anti-biofilm, and anti-virulence activity of the synthetic compound MTEBT-3 against carbapenem-resistant Klebsiella pneumoniae strains ST3984","authors":"Rui Zhang ,&nbsp;Yujie Liu ,&nbsp;Shiyu Wang ,&nbsp;Jianbang Kang ,&nbsp;Yan Song ,&nbsp;Donghong Yin ,&nbsp;Shuyun Wang ,&nbsp;Binbin Li ,&nbsp;Xiaoman Zhao ,&nbsp;Jinju Duan","doi":"10.1016/j.micpath.2024.107068","DOIUrl":"10.1016/j.micpath.2024.107068","url":null,"abstract":"<div><h3>Purpose</h3><div>The rise of carbapenem-resistant Klebsiella pneumoniae (CRKP) has led to increased morbidity and mortality in clinical patients, highlighting the urgent need for effective antibacterial agents.</div></div><div><h3>Methods</h3><div>We obtained a synthetic compound, MTEBT-3, using hydrophobic triphenylamine as the skeleton and hydrophilic ammonium salts. We determined the MIC of MTEBT-3 using the macro-broth susceptibility testing method. We isolated a clinical CRKP strain ST3984 and performed synergistic antibiotic sensitivity tests, time-kill assays, and resistance evolution studies. Biofilm formation under sub-MIC conditions was evaluated using crystal violet staining and CLSM. Additionally, biofilm proteins and polysaccharides were quantified. We assessed the bactericidal mechanism of MTEBT-3 by examining the integrity of CRKP bacterial cell membranes and analyzing the transcription of virulence-regulating genes via quantitative real-time PCR.</div></div><div><h3>Results</h3><div>MTEBT-3 exhibited broad-spectrum antibacterial activity with a low resistance rate, achieving the MIC of 8 μg/mL. The compound displayed additive effects with meropenem and imipenem and synergistic effects with tigecycline. It maintained its efficacy over multiple bacterial generations, with no significant increase in resistance observed. Under sub-MIC conditions, the biomass of biofilms was significantly reduced, and the levels of proteins and polysaccharides within the biofilms were markedly lowered in a concentration-dependent manner. The bactericidal mechanism of MTEBT-3 involved disrupting the integrity of CRKP bacterial cell membranes, leading to increased permeability. Quantitative real-time PCR results showed that MTEBT-3 effectively suppressed the expression of key virulence genes, including fimH, wbbM, rmpA, and rmpA2, which are associated with biofilm formation and bacterial adhesion.</div></div><div><h3>Conclusion</h3><div>The significant antimicrobial activity of MTEBT-3 against clinically isolated CRKP, along with its synergistic or additive effects with commonly used antibiotics, positions it as a promising candidate for treatment. Its ability to disrupt biofilm formation and reduce virulence factor expression further underscores its potential in managing CRKP infections.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"197 ","pages":"Article 107068"},"PeriodicalIF":3.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the efficacy of endophytic bacteria in controlling rice sheath blight: In vitro and In vivo studies","authors":"Sunera ,&nbsp;Zeeshan Khan ,&nbsp;Muhammad Irshad ,&nbsp;Muhammad Zakria ,&nbsp;Saddam Saqib ,&nbsp;Wajid Zaman","doi":"10.1016/j.micpath.2024.107084","DOIUrl":"10.1016/j.micpath.2024.107084","url":null,"abstract":"<div><div>Rice production is highly susceptible to various pathogens, including <em>Rhizoctonia solani</em>, <em>Curvularia lunata</em>, and <em>Epicoccum rostratum</em>, which are major threats in Asia. Exploring biological control methods using endophytic bacteria offers promising opportunities to enhance rice resilience against these lethal diseases. Using 16S RNA sequencing, we identified four endophytic isolates of <em>Bacillus</em> spp. from rice roots, stems, and leaves. We evaluated the antagonistic activity of these endophytic bacterial isolates against rice pathogens both <em>in vitro</em> and <em>in vivo</em>. These isolates inhibited the growth of <em>C. lunata</em> by 82 %, <em>R. solani</em> by 79 %, and <em>E. rostratum</em> by 88 % <em>in vitro</em>. The detached leaf assay for sheath blight (ShB) disease severity in strains ranged from 10.4 % to 73.3 %. <em>In vivo</em> results showed that <em>B. amyloliquefaciens</em> (R-19) exhibited the lowest disease intensity at 7.2 % and the highest disease suppression at 78.8 %. The fungicide propiconazole at 0.1 % treatment showed the lowest disease intensity of 7.7 % and the highest disease suppression of 73.4 %, compared to the infected control. Besides biocontrol efficacy, endophytic isolates enhance plant growth parameters, including shoot height, root length, fresh and dry weights, number of tillers, and grains per tiller. Plant hormones abscisic acid (ABA) and gibberellic acids (GA₃) increased by 35 % and 53 %, respectively, due to <em>B. subtilis</em> (R-20) and <em>B. amyloliquefaciens</em> (R-19), while flavonoid and indole acetic acid (IAA) concentrations surged by 30%–80 %. Similarly, chlorophyll (a, b), carotenoids, antioxidant enzymatic activity, phenolic content, carbohydrates, and proline contents were higher compared to the control. This study provides a foundation for future studies on novel and eco-friendly biocontrol agents. In addition, our study recommends the integration of endophytic bacteria into sustainable agriculture for enhancing rice production and reducing disease impacts.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"197 ","pages":"Article 107084"},"PeriodicalIF":3.3,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142539344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of erythromycin loaded PLGA nanoparticles for improved drug efficacy and sustained release against bacterial infections and biofilm formation","authors":"Kamal Mayattu,&nbsp;Jyutika Rajwade,&nbsp;Vandana Ghormade","doi":"10.1016/j.micpath.2024.107083","DOIUrl":"10.1016/j.micpath.2024.107083","url":null,"abstract":"<div><div>Bacterial infections are a common cause of sepsis, often leading to high patient mortality. Such infections are challenging to treat due to bacterial resistance to many existing drugs. Erythromycin (Ery) is a macrolide antibiotic used against bacterial infections with reported resistance. Recently, synthetic poly-lactide co-glycolic acid (PLGA) polymer nanoparticles (NPs) have displayed improved drug delivery characteristics and biocompatibility. In this study, PLGA-Ery NPs were synthesized by the o/w emulsion diffusion method, having a particle size of 159 ± 23 nm and displayed 71.89 % of encapsulation efficiency. The PLGA-Ery NPs showed 1.5, 2.1 and 1.5-fold improved MIC and antibacterial efficacy against <em>E. coli</em>, <em>S. aureus,</em> and <em>P. aeruginosa</em>, respectively than the pure drug. As illustrated by scanning electron microscopy, PLGA-Ery NPs caused damage to the bacterial cell walls. Furthermore, a surface coating with PLGA-Ery NPs on a glass surface showed efficient inhibition (&gt;90 %) of the biofilm formation by <em>P. aeruginosa,</em> as determined by fluorescence microscopy and MTT assay. This study demonstrates that PLGA-Ery NPs can increase the efficiency of erythromycin and can suppress the growth and biofilm formation of <em>P. aeruginosa</em>. Such polymeric nanoparticles drug nanoformulations have potential as an antimicrobial and as a surface coating for medical devices.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"197 ","pages":"Article 107083"},"PeriodicalIF":3.3,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptome analysis reveals the regulation of miR-19b on inflammation in bovine mammary epithelial cells","authors":"Yuhang Li ,&nbsp;Jian Yang ,&nbsp;Xingping Wang ,&nbsp;Zhuoma Luoreng","doi":"10.1016/j.micpath.2024.107082","DOIUrl":"10.1016/j.micpath.2024.107082","url":null,"abstract":"<div><div>MicroRNAs (miRNAs) are involved in various biological processes where they regulate the expression of mRNAs. Bovine mammary epithelial cells (bMECs) are functional cells that mediate mammary inflammatory immunity. Although numerous miRNAs regulate the function of bMECs, the role of miR-19b in bMECs has not been reported. In this study, the transcriptome of miR-19b overexpressed bMECs was analyzed by RNA-seq. Additionally, the differentially expressed genes (DEGs) were analyzed to establish the role of miR-19b in bMECs. The results revealed 269 DEGs between the miR-19b overexpression group and the negative control, including 199 up-regulated and 70 down-regulated genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that the DEGs regulated immune and inflammatory responses through <em>Staphylococcus aureus</em> (<em>S. aureus</em>) infection and phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway. In addition, the expression of miR-19b was significantly upregulated in lipophosphoric acid (LTA)-induced bMECs, and overexpression of miR-19b negatively regulated the expression of inflammatory cytokines <em>IL-1β</em> and <em>IL-6</em>, thereby alleviating the inflammatory response of LTA-induced bMECs. Based on the above results, we speculate that miR-19b may inhibit in dairy cow mammary inflammation caused by <em>S. aureus</em>, and this process may be mediated through the regulation of relevant gene expression and signaling pathways. The findings from this study provide a new reference for analyzing the molecular regulation of miR-19b in bMECs.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"197 ","pages":"Article 107082"},"PeriodicalIF":3.3,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibiofilm and antivirulence potentials of iodinated fmoc-phenylalanine against Staphylococcus aureus","authors":"Oluwatosin Oluwaseun Faleye,&nbsp;Jin-Hyung Lee,&nbsp;Yong-Guy Kim,&nbsp;Olajide Sunday Faleye,&nbsp;Jintae Lee","doi":"10.1016/j.micpath.2024.107080","DOIUrl":"10.1016/j.micpath.2024.107080","url":null,"abstract":"<div><div><em>Staphylococcus aureus</em> poses significant risks to public health due to its ability to form biofilm and produce virulence factors, contributing to the increase in antibiotic resistance and treatment complications. This emphasizes the urgent need for novel antimicrobial controls. Based on the premise that halogenation improves antimicrobial efficacy, this study investigated the ability of halogenated phenylalanine to effectively inhibit <em>S. aureus</em> biofilm formation and virulence activities. Among 29 halogenated compounds, Fmoc-4-iodo-phenylalanine (Fmoc-Iodo-Phe) displayed the highest antibiofilm effect against <em>S. aureus</em>, achieving 94.3 % reduction at 50 μg/mL. Microscopic studies confirmed its ability to prevent and disrupt mature biofilms. At 10 μg/mL, Fmoc-Iodo-Phe markedly inhibited virulence factors, such as cell surface hydrophobicity, hemolysin and slime production. It showed low propensity for resistance development and effectively inhibited biofilms formed by methicillin-resistant <em>S. aureus</em> (MRSA) and <em>S. epidermidis</em>, but was inactive against Gram-negative bacteria. Gene expression analysis complemented by molecular docking suggest that Fmoc-Iodo-Phe could target the AgrA quorum sensing cascade due to strong interactions with key residues at its DNA binding sites. Notably, it was non-cytotoxic in <em>Caenorhabditis elegans</em> model and satisfied drug-likeliness criteria based on ADMET prediction. Therefore, our findings position Fmoc-Iodo-Phe as a promising antimicrobial candidate against <em>S. aureus</em> infections, underscoring its potential as an alternative to traditional antibiotics.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"197 ","pages":"Article 107080"},"PeriodicalIF":3.3,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic effect of the combination of phenolic compounds and tobramycin on the inhibition of Pseudomonas aeruginosa biofilm","authors":"Emília Maria França Lima ,&nbsp;Vanessa Bueris ,&nbsp;Lígia Garcia Germano ,&nbsp;Marcelo Palma Sircili ,&nbsp;Uelinton Manoel Pinto","doi":"10.1016/j.micpath.2024.107079","DOIUrl":"10.1016/j.micpath.2024.107079","url":null,"abstract":"<div><div>Bacteria coordinate gene expression in a cell density-dependent manner using a communication process called quorum sensing (QS). The expression of virulence factors, biofilm formation and enzyme production are examples of QS-regulated phenotypes that can interfere with food quality and safety. Due to the importance of these phenotypes, the inhibition of bacterial communication as an anti-virulence strategy is of great interest. This work aimed to evaluate the effect of phenolic compounds on the inhibition of biofilm formation by <em>Pseudomonas aeruginosa</em> PAO1, using concentrations that do not interfere in bacterial growth. The synergistic effect of rosmarinic acid, baicalein, curcumin and resveratrol with tobramycin and between the phenolics themselves was evaluated. The tested combinations proved to be a good strategy for reducing the dose of antibiotics used in treatments and obtaining satisfactory results against <em>P. aeruginosa</em> biofilms. The combination of the four compounds at the highest concentration (500 μM) completely inhibited biofilm formation. The obtained results contribute to understanding the effect of phenolic compounds on QS inhibition, which may help to define the mechanism of inhibition, in addition to expanding the biotechnological potential of these compounds for future applications in the food, pharmaceutical and medical fields.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"197 ","pages":"Article 107079"},"PeriodicalIF":3.3,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}