首页 > 最新文献

Microbial pathogenesis最新文献

英文 中文
Molecular characterization of two phenotypes of Mixta calida isolated from post-liver transplant drainage fluid 肝移植后引流液中分离的两种表型calida的分子特征。
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-11-24 DOI: 10.1016/j.micpath.2025.108203
Bo Jiang , Xiaoyan Zhu , Yujie Lv , Yanmei Wang , Hongying Yang , Ya Yang , Yunmin Xu , Bin Shan , Guibo Song

Background

This study investigated the molecular basis of phenotypic variation between mucoid (mixA) and dry (mixB) Mixta calida strains from a liver transplant recipient.

Methods

Genomic analysis (comparative and pangenome), virulence/antibiotic resistance profiling, transcriptomic analysis, and quantitative biofilm assays were conducted.

Results

MixA and mixB showed >99.99 % sequence identity and extensive collinearity. Pangenome analysis identified mixA's unique CLUSTER3688 (O-antigen/teichoic acid export protein), suggesting altered cell surface modification. Virulence/resistance profiles and MICs were largely conserved. Significant differential gene expression occurred: mixA upregulated stress response and carbohydrate utilization genes, while downregulating sulfur metabolism, ABC transporters, ribosome, and peptidoglycan biosynthesis genes, suggesting lower metabolic activity. Biofilm assays showed no significant biomass difference, but mixA's unique surface export gene may influence structure.

Conclusions

The mucoid/dry phenotypic variation in Mixta calida appears driven by combined subtle genomic differences, including unique surface component export genes, and significant transcriptional reprogramming affecting key metabolic, stress response, and cell surface pathways. These findings are crucial for understanding this emerging pathogen's adaptation and pathogenesis.
背景:本研究探讨了肝移植受体黏液型(mixA)和干型(mixB) calida菌株表型差异的分子基础。方法:进行基因组分析(比较基因组和泛基因组)、毒力/抗生素耐药性分析、转录组分析和定量生物膜分析。结果:MixA和mixB具有99.99%的序列一致性和广泛的共线性。泛基因组分析鉴定出mixA独特的CLUSTER3688 (o -抗原/磷壁酸输出蛋白),提示细胞表面修饰发生改变。毒力/抗性谱和mic在很大程度上是保守的。发生了显著的基因表达差异:mixA上调应激反应和碳水化合物利用基因,下调硫代谢、ABC转运蛋白、核糖体和肽聚糖生物合成基因,表明代谢活性较低。生物膜实验显示生物量差异不显著,但mixA独特的表面输出基因可能会影响结构。结论:calida的黏液/干燥表型变异似乎是由微妙的基因组差异共同驱动的,包括独特的表面成分输出基因,以及影响关键代谢、应激反应和细胞表面途径的显著转录重编程。这些发现对于理解这种新兴病原体的适应和发病机制至关重要。
{"title":"Molecular characterization of two phenotypes of Mixta calida isolated from post-liver transplant drainage fluid","authors":"Bo Jiang ,&nbsp;Xiaoyan Zhu ,&nbsp;Yujie Lv ,&nbsp;Yanmei Wang ,&nbsp;Hongying Yang ,&nbsp;Ya Yang ,&nbsp;Yunmin Xu ,&nbsp;Bin Shan ,&nbsp;Guibo Song","doi":"10.1016/j.micpath.2025.108203","DOIUrl":"10.1016/j.micpath.2025.108203","url":null,"abstract":"<div><h3>Background</h3><div>This study investigated the molecular basis of phenotypic variation between mucoid (mixA) and dry (mixB) <em>Mixta calida</em> strains from a liver transplant recipient.</div></div><div><h3>Methods</h3><div>Genomic analysis (comparative and pangenome), virulence/antibiotic resistance profiling, transcriptomic analysis, and quantitative biofilm assays were conducted.</div></div><div><h3>Results</h3><div>MixA and mixB showed &gt;99.99 % sequence identity and extensive collinearity. Pangenome analysis identified mixA's unique CLUSTER3688 (O-antigen/teichoic acid export protein), suggesting altered cell surface modification. Virulence/resistance profiles and MICs were largely conserved. Significant differential gene expression occurred: mixA upregulated stress response and carbohydrate utilization genes, while downregulating sulfur metabolism, ABC transporters, ribosome, and peptidoglycan biosynthesis genes, suggesting lower metabolic activity. Biofilm assays showed no significant biomass difference, but mixA's unique surface export gene may influence structure.</div></div><div><h3>Conclusions</h3><div>The mucoid/dry phenotypic variation in <em>Mixta calida</em> appears driven by combined subtle genomic differences, including unique surface component export genes, and significant transcriptional reprogramming affecting key metabolic, stress response, and cell surface pathways. These findings are crucial for understanding this emerging pathogen's adaptation and pathogenesis.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"210 ","pages":"Article 108203"},"PeriodicalIF":3.5,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145635869","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}
引用次数: 0
A novel peptide antagonist for SATB1 in the immune response to Leishmania infection 一种新的SATB1肽拮抗剂在利什曼原虫感染的免疫应答中。
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-11-21 DOI: 10.1016/j.micpath.2025.108191
Diksha Jawale, Shailza Singh
Peptide-based therapies are emerging as powerful tools in the treatment of inflammatory and infectious diseases, offering high specificity, low toxicity, and minimal side effects. In this study, we identify Special AT-rich Binding Protein-1 (SATB1) as a novel immunotherapy target for cutaneous leishmaniasis (CL). As a global chromatin regulator, SATB1 is initially confined to the cytoplasm, but as infection progresses, it translocates to the nucleus, triggering Basic Helix-Loop-Helix Family Member E40 (Bhlehe40) - mediated Granulocyte-macrophage colony-stimulating factor (GM-CSF) production and inflammatory responses involving IL-6, IL-17, IL-23, and Sphingosine-1-phosphate (S1P). To restore immune balance, we strategically disrupt conserved residues Lysine (Lys) 29, Arginine (Arg) 32, Glutamic acid (Gln) 34, and Asparagine (Asn) 36 within SATB1's nuclear localization signal (NLS) using machine learning (ML) based peptide design approaches. Structural predictions, motif identification, and peptide library screening led to the selection of three peptide candidates (P1, P2, and P3) based on binding affinity and molecular interactions. Experimental validation identified P3 as the most effective peptide, successfully mitigating infection and re-establishing immune homeostasis in vitro and in vivo. This research underscores the potential of peptide-based therapeutics in developing targeted treatments for cutaneous leishmaniasis and other immune-related disorders.
基于肽的疗法正在成为治疗炎症性和感染性疾病的有力工具,具有高特异性、低毒性和最小副作用。在这项研究中,我们确定了特殊AT-rich Binding Protein-1 (SATB1)作为皮肤利什曼病(CL)的一种新的免疫治疗靶点。作为一种全球性的染色质调节剂,SATB1最初局限于细胞质,但随着感染的进展,它转运到细胞核,触发碱性螺旋-环-螺旋家族成员E40 (Bhlehe40)介导的粒细胞-巨噬细胞集落刺激因子(gmcsf)的产生和涉及IL-6、IL-17、IL-23和鞘鞘苷-1-磷酸(S1P)的炎症反应。为了恢复免疫平衡,我们使用基于机器学习(ML)的肽设计方法,战略性地破坏SATB1核定位信号(NLS)中的保守残基赖氨酸(Lys) 29、精氨酸(Arg) 32、谷氨酸(Gln) 34和天冬酰胺(Asn) 36。结构预测,基序鉴定和肽库筛选导致基于结合亲和力和分子相互作用选择三个候选肽(P1, P2和P3)。实验验证,P3是最有效的肽,可以成功地减轻感染,并在体外和体内重建免疫稳态。这项研究强调了基于肽的治疗方法在开发针对皮肤利什曼病和其他免疫相关疾病的靶向治疗方面的潜力。
{"title":"A novel peptide antagonist for SATB1 in the immune response to Leishmania infection","authors":"Diksha Jawale,&nbsp;Shailza Singh","doi":"10.1016/j.micpath.2025.108191","DOIUrl":"10.1016/j.micpath.2025.108191","url":null,"abstract":"<div><div>Peptide-based therapies are emerging as powerful tools in the treatment of inflammatory and infectious diseases, offering high specificity, low toxicity, and minimal side effects. In this study, we identify Special AT-rich Binding Protein-1 (SATB1) as a novel immunotherapy target for cutaneous leishmaniasis (CL). As a global chromatin regulator, SATB1 is initially confined to the cytoplasm, but as infection progresses, it translocates to the nucleus, triggering Basic Helix-Loop-Helix Family Member E40 (Bhlehe40) - mediated Granulocyte-macrophage colony-stimulating factor (GM-CSF) production and inflammatory responses involving IL-6, IL-17, IL-23, and Sphingosine-1-phosphate (S1P). To restore immune balance, we strategically disrupt conserved residues Lysine (Lys) 29, Arginine (Arg) 32, Glutamic acid (Gln) 34, and Asparagine (Asn) 36 within SATB1's nuclear localization signal (NLS) using machine learning (ML) based peptide design approaches. Structural predictions, motif identification, and peptide library screening led to the selection of three peptide candidates (P1, P2, and P3) based on binding affinity and molecular interactions. Experimental validation identified P3 as the most effective peptide, successfully mitigating infection and re-establishing immune homeostasis <em>in vitro</em> and <em>in vivo</em>. This research underscores the potential of peptide-based therapeutics in developing targeted treatments for cutaneous leishmaniasis and other immune-related disorders.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"210 ","pages":"Article 108191"},"PeriodicalIF":3.5,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145587927","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}
引用次数: 0
Identification and pathogenicity evaluation of Bacillus cereus isolated from dairy goats in China 中国奶山羊蜡样芽孢杆菌的鉴定及致病性评价。
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-11-20 DOI: 10.1016/j.micpath.2025.108199
Zhenpeng Li, Jie Wang, BaoShan Wang, Yongcheng Meng, Zhen Huang, Sihan Zuo, Wanling Yao, Wangdong Zhang
Bacillus cereus (B. cereus) eye infections in dairy goats cause conjunctivitis and keratitis, threatening animal welfare and productivity. To isolate B. cereus, evaluate its pathogenicity, and characterize its biological properties, we employed morphological observation, biochemical identification, 16S rRNA gene sequencing, specific gene detection, growth curve analysis, antimicrobial susceptibility testing, virulence gene screening, and histopathological examination of experimentally infected mice. The isolated strain was confirmed as B. cereus and designated LY. On Luria-Bertani (LB) agar, the isolate formed circular, convex, waxy-white colonies; on sheep blood agar, it exhibited non-hemolytic, light gray, ground-glass-like colonies. It was Gram-positive, with slender rods, subterminal spores, and occurring singly or in chains. Biochemical tests showed fermentation of glucose, maltose, fructose, and xylose, but not mannitol or sucrose; it was catalase-positive, urease-negative, H2S-negative, nitrate reduction-negative, and methyl red (MR)-positive. Growth analysis revealed optimal growth at pH 7.0 and 37 °C, with growth observed between pH 7.0–9.0 and 32–42 °C. Antimicrobial susceptibility testing revealed resistance to 11 antibiotics, including penicillin, vancomycin, and polymyxin B, and susceptibility to 14, such as amikacin, gentamicin, and kanamycin. PCR confirmed the presence of virulence genes plcR, hblC, hblD, nheA, nheB, nheC, and entFM, indicating high pathogenic potential. Histopathology of infected mice revealed severe hemorrhage in parenchymal organs (e.g., liver, kidney) and the gastrointestinal tract (e.g., stomach, intestine). In conclusion, LY, a B. cereus strain with multiple virulence genes, strong pathogenicity, and multidrug resistance, was isolated, indicating potential pathogenic risks to dairy goat herds.
蜡样芽孢杆菌(B. cereus)在奶山羊眼部感染引起结膜炎和角膜炎,威胁动物福利和生产力。通过形态学观察、生化鉴定、16S rRNA基因测序、特异性基因检测、生长曲线分析、药敏试验、毒力基因筛选和组织病理学检查,对实验感染小鼠进行蜡样芽孢杆菌的分离、致病性评价和生物学特性的研究。经鉴定为蜡样芽孢杆菌,命名为LY。在Luria-Bertani (LB)琼脂上,分离物形成圆形、凸形、蜡白色菌落;在羊血琼脂上,菌落呈浅灰色、非溶血性、磨玻璃样。革兰氏阳性,杆状体纤细,孢子亚顶,单发或链状。生化试验显示有葡萄糖、麦芽糖、果糖和木糖发酵,但没有甘露醇或蔗糖发酵;过氧化氢酶阳性,脲酶阴性,h2s阴性,硝酸盐还原阴性,甲基红(MR)阳性。生长分析显示pH 7.0和37°C时生长最佳,pH 7-9和32-42°C时生长最佳。药敏试验显示对青霉素、万古霉素和多粘菌素B等11种抗生素耐药,对阿米卡星、庆大霉素和卡那霉素等14种抗生素敏感。PCR证实存在毒力基因plcR、hblC、hblD、nheA、nheB、nheC和entFM,具有高致病性。感染小鼠的组织病理学显示实质器官(如肝、肾)和胃肠道(如胃、肠)严重出血。结论:分离到一株具有多毒力基因、强致病性、耐多药的蜡样芽孢杆菌LY,对奶山羊群具有潜在的致病风险。
{"title":"Identification and pathogenicity evaluation of Bacillus cereus isolated from dairy goats in China","authors":"Zhenpeng Li,&nbsp;Jie Wang,&nbsp;BaoShan Wang,&nbsp;Yongcheng Meng,&nbsp;Zhen Huang,&nbsp;Sihan Zuo,&nbsp;Wanling Yao,&nbsp;Wangdong Zhang","doi":"10.1016/j.micpath.2025.108199","DOIUrl":"10.1016/j.micpath.2025.108199","url":null,"abstract":"<div><div><em>Bacillus cereus</em> (<em>B. cereus</em>) eye infections in dairy goats cause conjunctivitis and keratitis, threatening animal welfare and productivity. To isolate <em>B. cereus</em>, evaluate its pathogenicity, and characterize its biological properties, we employed morphological observation, biochemical identification, 16S rRNA gene sequencing, specific gene detection, growth curve analysis, antimicrobial susceptibility testing, virulence gene screening, and histopathological examination of experimentally infected mice. The isolated strain was confirmed as <em>B</em>. <em>cereus</em> and designated LY. On Luria-Bertani (LB) agar, the isolate formed circular, convex, waxy-white colonies; on sheep blood agar, it exhibited non-hemolytic, light gray, ground-glass-like colonies. It was Gram-positive, with slender rods, subterminal spores, and occurring singly or in chains. Biochemical tests showed fermentation of glucose, maltose, fructose, and xylose, but not mannitol or sucrose; it was catalase-positive, urease-negative, H<sub>2</sub>S-negative, nitrate reduction-negative, and methyl red (MR)-positive. Growth analysis revealed optimal growth at pH 7.0 and 37 °C, with growth observed between pH 7.0–9.0 and 32–42 °C. Antimicrobial susceptibility testing revealed resistance to 11 antibiotics, including penicillin, vancomycin, and polymyxin B, and susceptibility to 14, such as amikacin, gentamicin, and kanamycin. PCR confirmed the presence of virulence genes <em>plcR</em>, <em>hblC</em>, <em>hblD</em>, <em>nheA</em>, <em>nheB</em>, <em>nheC</em>, and <em>entFM</em>, indicating high pathogenic potential. Histopathology of infected mice revealed severe hemorrhage in parenchymal organs (e.g., liver, kidney) and the gastrointestinal tract (e.g., stomach, intestine). In conclusion, LY, a B. cereus strain with multiple virulence genes, strong pathogenicity, and multidrug resistance, was isolated, indicating potential pathogenic risks to dairy goat herds.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"210 ","pages":"Article 108199"},"PeriodicalIF":3.5,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145582601","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}
引用次数: 0
Bioengineered selenium nanoparticles synthesized using Ficus hispida ethyl acetate extract exhibit antibacterial and antioxidant activities 利用榕叶乙酸乙酯提取物合成的生物工程硒纳米颗粒具有抗菌和抗氧化活性。
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-11-20 DOI: 10.1016/j.micpath.2025.108202
Jatla Murali Prakash , Palanisamy Pethappachetty , Raslamol Kannurkaran , Shilpa Valiyaparambil , Deepti Kolli

Background

The emergence of multidrug-resistant bacteria necessitates the development of novel antimicrobial agents. Selenium nanoparticles (Se-NPs) synthesized via green methods offer promising antioxidant and antibacterial properties. Aim: This study investigates the synthesis, characterization, and bioactivity of Se-NPs mediated by Ficus hispida extract. Methodology: Ficus hispida fruit extract was used to synthesize Se-NPs by mixing 10 mL of the extract with 20 mL of 50 mM selenium solution, followed by reduction with 200 μL of 40 mM ascorbic acid. The formation of Se-NPs was confirmed by a ruby red color. Characterization was performed using UV–Vis spectroscopy (peaks at 203 nm and 257 nm), FT-IR (bands at 3362, 3245, 1648, 1383, 1202 cm−1), XRD (2θ: 23.5°, 29.7°, 41.4°, 43.6°, 45.4°, 51.7°, 55.9°, 61.5°), FE-SEM (particle size: 71.73–98.81 nm), HR-TEM (7.59–12.26 nm), zeta potential analysis (−37.1 mV), and EDAX (Se and O peaks). Antioxidant activity was assessed via DPPH assay, and antibacterial activity was evaluated by agar well diffusion against Escherichia coli, Bacillus subtilis, and Staphylococcus aureus.

Results

Se-NPs showed strong surface plasmon resonance and high crystallinity with hexagonal structure. They were predominantly spherical, monodispersed, and exhibited excellent colloidal stability. Antioxidant activity reached 71 % inhibition at 100 μg/mL, while ascorbic acid achieved 98.22 %. Antibacterial tests revealed inhibition zones of 14 mm (E. coli, B. subtilis) and 18 mm (S. aureus), compared to ciprofloxacin's 31–32 mm. HR-TEM of S. aureus treated with Se-NPs showed significant morphological alterations.

Conclusion

Ficus hispida-mediated Se-NPs are eco-friendly, well-characterised, and display notable antioxidant and antibacterial activities, especially against Gram-positive bacteria. These findings support further biomedical exploration of FH-Se-NPs as alternative therapeutic agents.
背景:耐多药细菌的出现要求开发新型抗菌药物。通过绿色方法合成的硒纳米颗粒具有良好的抗氧化和抗菌性能。目的:研究榕叶提取物介导Se-NPs的合成、表征及其生物活性。方法:以榕果提取物10 mL与50 mM硒溶液20 mL混合,用40 mM抗坏血酸200 μL还原,合成Se-NPs。Se-NPs的形成被红宝石色证实。采用UV-Vis光谱(峰为203 nm和257 nm)、FT-IR(峰为3362、3245、1648、1383、1202 cm-1)、XRD (2θ: 23.5°、29.7°、41.4°、43.6°、45.4°、51.7°、55.9°、61.5°)、FE-SEM(粒径:71.73 ~ 98.81 nm)、HR-TEM(峰为7.59 ~ 12.26 nm)、zeta电位分析(-37.1 mV)和EDAX (Se和O峰)进行表征。DPPH法测定抗氧化活性,琼脂孔扩散法测定对大肠杆菌、枯草芽孢杆菌和金黄色葡萄球菌的抑菌活性。结果:Se-NPs具有强表面等离子共振和高结晶度的六方结构。它们主要呈球形,单分散,并表现出优异的胶体稳定性。在100 μg/mL时,抗坏血酸抑制率为98.22%,抗氧化活性为71%。抗菌试验显示,环丙沙星的抑制区为14 mm(大肠杆菌、枯草芽孢杆菌)和18 mm(金黄色葡萄球菌),而环丙沙星的抑制区为31-32 mm。经Se-NPs处理的金黄色葡萄球菌的HR-TEM表现出明显的形态学改变。结论:榕叶多糖介导的Se-NPs具有良好的抗氧化和抗菌活性,对革兰氏阳性菌具有显著的抗氧化和抗菌活性。这些发现支持了FH-Se-NPs作为替代治疗剂的进一步生物医学探索。
{"title":"Bioengineered selenium nanoparticles synthesized using Ficus hispida ethyl acetate extract exhibit antibacterial and antioxidant activities","authors":"Jatla Murali Prakash ,&nbsp;Palanisamy Pethappachetty ,&nbsp;Raslamol Kannurkaran ,&nbsp;Shilpa Valiyaparambil ,&nbsp;Deepti Kolli","doi":"10.1016/j.micpath.2025.108202","DOIUrl":"10.1016/j.micpath.2025.108202","url":null,"abstract":"<div><h3>Background</h3><div>The emergence of multidrug-resistant bacteria necessitates the development of novel antimicrobial agents. Selenium nanoparticles (Se-NPs) synthesized via green methods offer promising antioxidant and antibacterial properties. <strong>Aim</strong>: This study investigates the synthesis, characterization, and bioactivity of Se-NPs mediated by Ficus hispida extract. <strong>Methodology</strong>: Ficus hispida fruit extract was used to synthesize Se-NPs by mixing 10 mL of the extract with 20 mL of 50 mM selenium solution, followed by reduction with 200 μL of 40 mM ascorbic acid. The formation of Se-NPs was confirmed by a ruby red color. Characterization was performed using UV–Vis spectroscopy (peaks at 203 nm and 257 nm), FT-IR (bands at 3362, 3245, 1648, 1383, 1202 cm<sup>−1</sup>), XRD (2θ: 23.5°, 29.7°, 41.4°, 43.6°, 45.4°, 51.7°, 55.9°, 61.5°), FE-SEM (particle size: 71.73–98.81 nm), HR-TEM (7.59–12.26 nm), zeta potential analysis (−37.1 mV), and EDAX (Se and O peaks). Antioxidant activity was assessed via DPPH assay, and antibacterial activity was evaluated by agar well diffusion against <em>Escherichia coli</em>, Bacillus subtilis, and <em>Staphylococcus aureus</em>.</div></div><div><h3>Results</h3><div>Se-NPs showed strong surface plasmon resonance and high crystallinity with hexagonal structure. They were predominantly spherical, monodispersed, and exhibited excellent colloidal stability. Antioxidant activity reached 71 % inhibition at 100 μg/mL, while ascorbic acid achieved 98.22 %. Antibacterial tests revealed inhibition zones of 14 mm (<em>E. coli</em>, <em>B. subtilis</em>) and 18 mm (<em>S. aureus</em>), compared to ciprofloxacin's 31–32 mm. HR-TEM of <em>S. aureus</em> treated with Se-NPs showed significant morphological alterations.</div></div><div><h3>Conclusion</h3><div>Ficus hispida-mediated Se-NPs are eco-friendly, well-characterised, and display notable antioxidant and antibacterial activities, especially against Gram-positive bacteria. These findings support further biomedical exploration of FH-Se-NPs as alternative therapeutic agents.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"210 ","pages":"Article 108202"},"PeriodicalIF":3.5,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145582501","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}
引用次数: 0
Screening for novel therapeutic agents targeting multidrug-resistant Klebsiella pneumoniae 针对多药耐药肺炎克雷伯菌的新型治疗药物筛选。
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-11-20 DOI: 10.1016/j.micpath.2025.108186
José Eduardo Souza Echeverria , Jean Carlos Pael Vicente , Matheus Simplício Sena, Pedro Julio Franco Camilo, Mariana Carvalho Sturaro, Fabíola Lucini, Lisset Ortiz-Zamora, Luana Rossato, Ruana Carolina Cabral da Silva, Simone Simionatto
The occurrence of antimicrobial resistance, a major global health threat, can be attributed to the emergence of multidrug-resistant (MDR) Gram-negative bacteria, such as Klebsiella pneumoniae. To improve the therapeutic arsenal against MDR pathogens, this study evaluated the antibacterial activities of 240 compounds from the Global Health Priority Box (GHPB) against an MDR K. pneumoniae strain. In particular, this study examined the inhibitory concentrations of GHPB compounds and their antimicrobial synergy with polymyxin B (PMB) and effects on membrane permeability, nucleic acid and protein leakage, and the production of reactive oxygen species. Ultra-structural changes were investigated using scanning electron microscopy. The safety of compounds was evaluated using the hemolysis and Caenorhabditis elegans-based assays. Additionally, molecular docking analyses and pharmacokinetic parameter prediction were performed. Two compounds (MMV1794211 (M11) and MMV006187 (M18)) in combination with PMB exerted synergistic antimicrobial effects. The combination of M11 or M18 and PMB was associated with low toxicity. M11 and M18 interacted with DNA gyrase. Pharmacokinetic analysis revealed that M11 and M18 can be administered via the oral and parenteral routes, respectively. These findings suggest that M11 and M18, in combination with PMB are promising candidates for further preclinical evaluation against MDR K. pneumoniae infections.
抗菌素耐药性是一项重大的全球健康威胁,其发生可归因于肺炎克雷伯菌等多重耐药革兰氏阴性细菌的出现。为了提高对耐多药病原菌的治疗武库,本研究评估了全球卫生优先箱(GHPB)中240种化合物对耐多药肺炎克雷伯菌菌株的抗菌活性。本研究特别研究了GHPB化合物的抑制浓度及其与多粘菌素B (PMB)的抗菌协同作用,以及对膜通透性、核酸和蛋白质泄漏以及活性氧产生的影响。用扫描电镜观察其超微结构变化。采用溶血试验和秀丽隐杆线虫试验评价化合物的安全性。此外,还进行了分子对接分析和药代动力学参数预测。两种化合物MMV1794211 (M11)和MMV006187 (M18)与PMB联用具有协同抑菌作用。M11或M18与PMB联合使用毒性较低。M11和M18与DNA旋切酶相互作用。药代动力学分析显示,M11和M18可分别通过口服和肠外给药。这些发现表明,M11和M18联合PMB是进一步临床前评估抗耐多药肺炎克雷伯菌感染的有希望的候选药物。
{"title":"Screening for novel therapeutic agents targeting multidrug-resistant Klebsiella pneumoniae","authors":"José Eduardo Souza Echeverria ,&nbsp;Jean Carlos Pael Vicente ,&nbsp;Matheus Simplício Sena,&nbsp;Pedro Julio Franco Camilo,&nbsp;Mariana Carvalho Sturaro,&nbsp;Fabíola Lucini,&nbsp;Lisset Ortiz-Zamora,&nbsp;Luana Rossato,&nbsp;Ruana Carolina Cabral da Silva,&nbsp;Simone Simionatto","doi":"10.1016/j.micpath.2025.108186","DOIUrl":"10.1016/j.micpath.2025.108186","url":null,"abstract":"<div><div>The occurrence of antimicrobial resistance, a major global health threat, can be attributed to the emergence of multidrug-resistant (MDR) Gram-negative bacteria, such as <em>Klebsiella pneumoniae</em>. To improve the therapeutic arsenal against MDR pathogens, this study evaluated the antibacterial activities of 240 compounds from the Global Health Priority Box (GHPB) against an MDR <em>K. pneumoniae</em> strain. In particular, this study examined the inhibitory concentrations of GHPB compounds and their antimicrobial synergy with polymyxin B (PMB) and effects on membrane permeability, nucleic acid and protein leakage, and the production of reactive oxygen species. Ultra-structural changes were investigated using scanning electron microscopy. The safety of compounds was evaluated using the hemolysis and <em>Caenorhabditis elegans</em>-based assays. Additionally, molecular docking analyses and pharmacokinetic parameter prediction were performed. Two compounds (MMV1794211 (M11) and MMV006187 (M18)) in combination with PMB exerted synergistic antimicrobial effects. The combination of M11 or M18 and PMB was associated with low toxicity. M11 and M18 interacted with DNA gyrase. Pharmacokinetic analysis revealed that M11 and M18 can be administered via the oral and parenteral routes, respectively. These findings suggest that M11 and M18, in combination with PMB are promising candidates for further preclinical evaluation against MDR <em>K. pneumoniae</em> infections.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"210 ","pages":"Article 108186"},"PeriodicalIF":3.5,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145582553","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}
引用次数: 0
Lycopene nanoparticles deliver targeted improvements in broilers’ performance, immune competence, antioxidant defense, and resistance against Pasteurella multocida infection 番茄红素纳米颗粒可有针对性地提高肉鸡的生产性能、免疫能力、抗氧化防御能力和对多杀性巴氏杆菌感染的抵抗力。
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-11-19 DOI: 10.1016/j.micpath.2025.108200
Marwa I. Abd El-Hamid , Azza S. El-Demerdash , Rania M.S. El-Malt , Saqer S. Alotaibi , Mohammed E.E. Sayed Ahmed , Shaimaa A. Abd El-Kader , Manal A.M. Habaka , Dalia Ibrahim Mohamed , Mona S. Ibrahim , Dalia Kamel Zaki , Sherief M. Abdel-Raheem , Essam H. Elderhmy , Doaa Ibrahim
Avian pasteurellosis induced by Pasteurella multocida is marked by suboptimal performance and elevated mortality rates in broilers. An innovative dietary intervention utilizing lycopene-NPs was assessed for its efficacy on growth performance, general well-being, immune system, antioxidant capacity, and resistance to P. multocida in broilers. Five equal groups consisting of 250 broilers were administered either a basal diet or diets enriched with lycopene-NPs at levels of 50, 100, and 150 mg/kg and were experimentally infected with a multidrug-resistant and multi-virulent P. multocida strain at 28 d of age. The incorporation of dietary lycopene-NPs, particularly at higher levels, significantly diminished P. multocida colonization, abundance, and the transcription of its virulence genes (pfhA, exbB, ompA, sodA, and sodC), thereby ameliorating the compromised growth performance and lung histomorphological alterations in challenged broilers. Broilers fortified with lycopene-NPs, particularly at a dosage of 150 mg/kg, exhibited downregulation of inflammation-regulated genes (IL-1β, IL-6, TNF-α, CCL4, CCL20, and CD36), and upregulation of mucosal barrier gene (MUC2). The lung redox balance improved due to the overexpression of NQO1, HO-1, and Nrf2 genes, and an elevation in the levels of T-AOC, GPX, SOD, and CAT enzymes, accompanied by a concurrent downregulation in the COX2 gene, besides reductions in H2O2, ROS, and MDA levels in broilers offered 150 mg/kg lycopene-NPs. Ultimately, novel dietary intervention with lycopene-NPs significantly enhanced immunological and antioxidant potential, mitigated avian pasteurellosis, and improved performance and overall health in challenged broilers.
多杀性巴氏杆菌引起的禽巴氏杆菌病在肉鸡中表现为生产性能不佳和死亡率升高。利用番茄红素nps对肉鸡生长性能、总体健康状况、免疫系统、抗氧化能力和对多毒杆菌抗性的影响进行了评估。每组250只肉仔鸡分别饲喂基础饲粮和富含番茄红素nps(50、100和150 mg/kg)的饲粮,并在28日龄时感染一种多重耐药、多重毒力的多毒杆菌。饲粮中加入番茄红素- nps,特别是高水平的番茄红素- nps,可显著减少多杀弧菌的定植、丰度及其毒力基因(pfhA、exbB、ompA、sodA和sodC)的转录,从而改善受感染肉鸡的生长性能和肺部组织形态学改变。番茄红素nps添加量为150 mg/kg时,肉鸡炎症调节基因(IL-1β、IL-6、TNF-α、CCL4、CCL20和CD36)表达下调,粘膜屏障基因(MUC2)表达上调。在150 mg/kg番茄红素nps组中,NQO1、HO-1和Nrf2基因过表达,T-AOC、GPX、SOD和CAT酶水平升高,COX2基因同时下调,H2O2、ROS和MDA水平降低,改善了肺氧化还原平衡。最终,番茄红素- nps的新型饲粮干预显著增强了挑战肉鸡的免疫和抗氧化能力,减轻了禽类巴氏杆菌病,改善了生产性能和整体健康状况。
{"title":"Lycopene nanoparticles deliver targeted improvements in broilers’ performance, immune competence, antioxidant defense, and resistance against Pasteurella multocida infection","authors":"Marwa I. Abd El-Hamid ,&nbsp;Azza S. El-Demerdash ,&nbsp;Rania M.S. El-Malt ,&nbsp;Saqer S. Alotaibi ,&nbsp;Mohammed E.E. Sayed Ahmed ,&nbsp;Shaimaa A. Abd El-Kader ,&nbsp;Manal A.M. Habaka ,&nbsp;Dalia Ibrahim Mohamed ,&nbsp;Mona S. Ibrahim ,&nbsp;Dalia Kamel Zaki ,&nbsp;Sherief M. Abdel-Raheem ,&nbsp;Essam H. Elderhmy ,&nbsp;Doaa Ibrahim","doi":"10.1016/j.micpath.2025.108200","DOIUrl":"10.1016/j.micpath.2025.108200","url":null,"abstract":"<div><div>Avian pasteurellosis induced by <em>Pasteurella multocida</em> is marked by suboptimal performance and elevated mortality rates in broilers. An innovative dietary intervention utilizing lycopene-NPs was assessed for its efficacy on growth performance, general well-being, immune system, antioxidant capacity, and resistance to <em>P. multocida</em> in broilers. Five equal groups consisting of 250 broilers were administered either a basal diet or diets enriched with lycopene-NPs at levels of 50, 100, and 150 mg/kg and were experimentally infected with a multidrug-resistant and multi-virulent <em>P. multocida</em> strain at 28 d of age. The incorporation of dietary lycopene-NPs, particularly at higher levels, significantly diminished <em>P. multocida</em> colonization, abundance, and the transcription of its virulence genes (<em>pfhA, exbB, ompA, sodA</em>, and <em>sodC</em>), thereby ameliorating the compromised growth performance and lung histomorphological alterations in challenged broilers. Broilers fortified with lycopene-NPs, particularly at a dosage of 150 mg/kg, exhibited downregulation of inflammation-regulated genes (<em>IL-1β, IL-6, TNF-α, CCL4, CCL20</em>, and <em>CD36</em>), and upregulation of mucosal barrier gene (<em>MUC2</em>). The lung redox balance improved due to the overexpression of <em>NQO1, HO-1,</em> and <em>Nrf2</em> genes, and an elevation in the levels of T-AOC, GPX, SOD, and CAT enzymes, accompanied by a concurrent downregulation in the <em>COX2</em> gene, besides reductions in H<sub>2</sub>O<sub>2</sub>, ROS, and MDA levels in broilers offered 150 mg/kg lycopene-NPs. Ultimately, novel dietary intervention with lycopene-NPs significantly enhanced immunological and antioxidant potential, mitigated avian pasteurellosis, and improved performance and overall health in challenged broilers.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"210 ","pages":"Article 108200"},"PeriodicalIF":3.5,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145573613","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}
引用次数: 0
Diversity, distribution, and climate change impacts on tick fauna in Saudi Arabia: A comprehensive ecological niche modeling approach 多样性、分布和气候变化对沙特阿拉伯蜱动物群的影响:一个全面的生态位建模方法
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-11-19 DOI: 10.1016/j.micpath.2025.108201
Abdullah D. Alanazi , Hanadi B. Baghdadi , Mohamed Abdelsalam , Hanen Chakroun
Ticks are obligate hematophagous ectoparasites that serve as significant vectors of pathogens affecting human and animal health globally. Despite their medical and veterinary importance in Saudi Arabia—a region experiencing rapid socio-economic transformations—comprehensive documentation of tick diversity and distribution patterns remains fragmented. This study systematically documented tick diversity and predicted current and future distributions using ecological niche modeling (ENM). We conducted a systematic literature review spanning 1979–2023, compiling 205 geospatial records across Saudi Arabia. Using nine modeling algorithms implemented in R environment, we assessed current ecological niches and projected future distributions under Representative Concentration Pathway (RCP) climate change scenarios for 2050 and 2070. The analysis identified 35 tick species across six genera, with Hyalomma and Rhipicephalus dominating the fauna. Hyalomma dromedarii, H. impeltatum, and Rhipicephalus turanicus emerged as the most prevalent species, showing increasing documentation trends particularly after 1993. Ecological niche models achieved exceptional accuracy (AUC values 0.86–0.99), identifying annual precipitation (Bio12) and mean annual temperature (Bio1) as primary distribution drivers. Climate projections revealed complex regional shifts in habitat suitability rather than uniform changes, with northern and coastal regions showing mixed patterns. The dominance of species transmitting Crimean-Congo hemorrhagic fever virus, Rickettsia, and Coxiella burnetii poses significant public health concerns. These findings support Saudi Vision 2030's sustainable development goals by enabling evidence-based land use planning, targeted disease surveillance, and integrated tick management strategies essential for protecting human and animal health amid ongoing environmental changes.
蜱是专性食血体外寄生虫,是影响全球人类和动物健康的病原体的重要载体。尽管蜱虫在沙特阿拉伯这一经历快速社会经济转型的地区具有重要的医学和兽医意义,但关于蜱虫多样性和分布模式的全面记录仍然支离破碎。本研究系统地记录了蜱的多样性,并利用生态位模型(ENM)预测了当前和未来的分布。我们对1979-2023年间的文献进行了系统的回顾,汇编了沙特阿拉伯的205个地理空间记录。利用R环境中实现的9种建模算法,对2050年和2070年代表性浓度路径(Representative Concentration Pathway, RCP)气候变化情景下的生态位和未来分布进行了评估。分析确定了6属35种蜱,以透明蜱和鼻头蜱为主。单眼透明蝇、刺眼透明蝇和图兰鼻头蝇是最常见的物种,特别是1993年以后,文献记录呈增加趋势。生态位模型的AUC值为0.86 ~ 0.99,表明年降水量(Bio12)和年平均温度(Bio1)是主要的分布驱动因素。气候预测显示,栖息地适宜性的区域变化复杂,而不是统一的变化,北部和沿海地区呈现混合模式。传播克里米亚-刚果出血热病毒、立克次体和伯氏柯谢氏菌的主要物种构成了重大的公共卫生问题。这些发现支持了沙特2030年愿景的可持续发展目标,实现了以证据为基础的土地利用规划、有针对性的疾病监测和综合蜱虫管理战略,这些战略对于在持续的环境变化中保护人类和动物健康至关重要。
{"title":"Diversity, distribution, and climate change impacts on tick fauna in Saudi Arabia: A comprehensive ecological niche modeling approach","authors":"Abdullah D. Alanazi ,&nbsp;Hanadi B. Baghdadi ,&nbsp;Mohamed Abdelsalam ,&nbsp;Hanen Chakroun","doi":"10.1016/j.micpath.2025.108201","DOIUrl":"10.1016/j.micpath.2025.108201","url":null,"abstract":"<div><div>Ticks are obligate hematophagous ectoparasites that serve as significant vectors of pathogens affecting human and animal health globally. Despite their medical and veterinary importance in Saudi Arabia—a region experiencing rapid socio-economic transformations—comprehensive documentation of tick diversity and distribution patterns remains fragmented. This study systematically documented tick diversity and predicted current and future distributions using ecological niche modeling (ENM). We conducted a systematic literature review spanning 1979–2023, compiling 205 geospatial records across Saudi Arabia. Using nine modeling algorithms implemented in R environment, we assessed current ecological niches and projected future distributions under Representative Concentration Pathway (RCP) climate change scenarios for 2050 and 2070. The analysis identified 35 tick species across six genera, with <em>Hyalomma</em> and <em>Rhipicephalus</em> dominating the fauna. <em>Hyalomma dromedarii</em>, <em>H. impeltatum</em>, and <em>Rhipicephalus turanicus</em> emerged as the most prevalent species, showing increasing documentation trends particularly after 1993. Ecological niche models achieved exceptional accuracy (AUC values 0.86–0.99), identifying annual precipitation (Bio12) and mean annual temperature (Bio1) as primary distribution drivers. Climate projections revealed complex regional shifts in habitat suitability rather than uniform changes, with northern and coastal regions showing mixed patterns. The dominance of species transmitting Crimean-Congo hemorrhagic fever virus, <em>Rickettsia</em>, and <em>Coxiella burnetii</em> poses significant public health concerns. These findings support Saudi Vision 2030's sustainable development goals by enabling evidence-based land use planning, targeted disease surveillance, and integrated tick management strategies essential for protecting human and animal health amid ongoing environmental changes.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"210 ","pages":"Article 108201"},"PeriodicalIF":3.5,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145569198","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}
引用次数: 0
Multi-omic analysis reveals lysine acylation and biofilm formation induced by central metabolites in methicillin-resistant Staphylococcus aureus 多组学分析显示耐甲氧西林金黄色葡萄球菌中心代谢物诱导赖氨酸酰化和生物膜形成。
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-11-19 DOI: 10.1016/j.micpath.2025.108198
Changxia Zhou , Mengying Chen , Rongzhen Wang , Xia Liu , Dabang Tian , Mei Xiao , Huiling Liu , Tian Tian , Yewen Sun , Minjia Tan , Jun-Yu Xu
Methicillin-resistant Staphylococcus aureus (MRSA) is a major multidrug-resistant pathogen responsible for severe infections, such as pneumonia and bloodstream infections. These infections are often associated with high mortality rates and pose a significant burden on public health. Studies have shown that biofilm formation is a key factor contributing to its enhanced drug resistance. Recent evidence also implicates core metabolites in biofilm regulation. However, their specific regulatory mechanisms remain unclear. In this study, we initially assessed how key metabolites from glycolysis and the tricarboxylic acid (TCA) cycle influenced MRSA physiology. Notably, glucose markedly enhanced bacterial proliferation and stimulated biofilm development. To further explore the molecular basis of glucose-induced changes in MRSA, we subsequently applied a multidimensional omics approach, including proteomics, acetylomics, succinylomics, and lactylomics. A total of 1666 proteins, 3761 lysine acetylated sites, 1809 succinylated sites, and 128 lactylated sites were identified by high-resolution mass spectrometry. Subsequent bioinformatic analysis revealed that these modifications were significantly enriched in ribosome-associated functions and metabolic pathways. To further explore their functional relevance, in vitro enzyme assays demonstrated that glucose-induced lysine succinylation modulates the activity of arsenate reductase. Building upon this, functional validation at both the bacterial and host cell levels confirmed the physiological significance of glucose-induced lysine acylation. In conclusion, these findings reveal that the core metabolite glucose promotes MRSA biofilm formation and induces extensive lysine acylation, which in turn regulates metabolic functions and virulence. Therefore, this study provides new insights into MRSA pathogenesis and suggests potential targets for anti-infective therapy.
耐甲氧西林金黄色葡萄球菌(MRSA)是一种主要的多重耐药病原体,可导致肺炎和血液感染等严重感染。这些感染往往与高死亡率有关,并对公共卫生造成重大负担。研究表明,生物膜的形成是其增强耐药性的关键因素。最近的证据也表明核心代谢物参与了生物膜的调节。然而,它们的具体监管机制尚不清楚。在这项研究中,我们初步评估了糖酵解和三羧酸(TCA)循环的关键代谢物如何影响MRSA生理学。值得注意的是,葡萄糖显著促进细菌增殖和刺激生物膜的发育。为了进一步探索葡萄糖诱导MRSA变化的分子基础,我们随后应用了多维组学方法,包括蛋白质组学、乙酰组学、琥珀组学和乳酸组学。通过高分辨率质谱分析,共鉴定出1666个蛋白、3761个赖氨酸乙酰化位点、1809个琥珀化位点和128个乳酸化位点。随后的生物信息学分析显示,这些修饰在核糖体相关功能和代谢途径中显著富集。为了进一步探讨它们的功能相关性,体外酶分析表明,葡萄糖诱导的赖氨酸琥珀酰化可调节砷酸盐还原酶的活性。在此基础上,在细菌和宿主细胞水平上的功能验证证实了葡萄糖诱导的赖氨酸酰化的生理意义。综上所述,这些发现表明核心代谢物葡萄糖促进MRSA生物膜的形成并诱导广泛的赖氨酸酰化,从而调节代谢功能和毒力。因此,该研究为MRSA的发病机制提供了新的见解,并为抗感染治疗提供了潜在的靶点。
{"title":"Multi-omic analysis reveals lysine acylation and biofilm formation induced by central metabolites in methicillin-resistant Staphylococcus aureus","authors":"Changxia Zhou ,&nbsp;Mengying Chen ,&nbsp;Rongzhen Wang ,&nbsp;Xia Liu ,&nbsp;Dabang Tian ,&nbsp;Mei Xiao ,&nbsp;Huiling Liu ,&nbsp;Tian Tian ,&nbsp;Yewen Sun ,&nbsp;Minjia Tan ,&nbsp;Jun-Yu Xu","doi":"10.1016/j.micpath.2025.108198","DOIUrl":"10.1016/j.micpath.2025.108198","url":null,"abstract":"<div><div>Methicillin-resistant <em>Staphylococcus aureus</em> (MRSA) is a major multidrug-resistant pathogen responsible for severe infections, such as pneumonia and bloodstream infections. These infections are often associated with high mortality rates and pose a significant burden on public health. Studies have shown that biofilm formation is a key factor contributing to its enhanced drug resistance. Recent evidence also implicates core metabolites in biofilm regulation. However, their specific regulatory mechanisms remain unclear. In this study, we initially assessed how key metabolites from glycolysis and the tricarboxylic acid (TCA) cycle influenced MRSA physiology. Notably, glucose markedly enhanced bacterial proliferation and stimulated biofilm development. To further explore the molecular basis of glucose-induced changes in MRSA, we subsequently applied a multidimensional omics approach, including proteomics, acetylomics, succinylomics, and lactylomics. A total of 1666 proteins, 3761 lysine acetylated sites, 1809 succinylated sites, and 128 lactylated sites were identified by high-resolution mass spectrometry. Subsequent bioinformatic analysis revealed that these modifications were significantly enriched in ribosome-associated functions and metabolic pathways. To further explore their functional relevance, <em>in vitro</em> enzyme assays demonstrated that glucose-induced lysine succinylation modulates the activity of arsenate reductase. Building upon this, functional validation at both the bacterial and host cell levels confirmed the physiological significance of glucose-induced lysine acylation. In conclusion, these findings reveal that the core metabolite glucose promotes MRSA biofilm formation and induces extensive lysine acylation, which in turn regulates metabolic functions and virulence. Therefore, this study provides new insights into MRSA pathogenesis and suggests potential targets for anti-infective therapy.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"210 ","pages":"Article 108198"},"PeriodicalIF":3.5,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145573638","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}
引用次数: 0
Corrigendum to “Design of recombinant bacteriocin fusion protein and evaluation of its anticancer and antibacterial activity” [Microb. Pathog. 205 (2025) 107633] “重组细菌素融合蛋白的设计及其抗癌和抗菌活性的评价”[微生物]。中华病理学杂志,205 (2025)107633 [j]。
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-11-19 DOI: 10.1016/j.micpath.2025.108161
Narges Yadollahi Movahed , Taher Mohamadian , Davoud Esmaeili , Fatemeh Foroohi , Payam Behzadi
{"title":"Corrigendum to “Design of recombinant bacteriocin fusion protein and evaluation of its anticancer and antibacterial activity” [Microb. Pathog. 205 (2025) 107633]","authors":"Narges Yadollahi Movahed ,&nbsp;Taher Mohamadian ,&nbsp;Davoud Esmaeili ,&nbsp;Fatemeh Foroohi ,&nbsp;Payam Behzadi","doi":"10.1016/j.micpath.2025.108161","DOIUrl":"10.1016/j.micpath.2025.108161","url":null,"abstract":"","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"210 ","pages":"Article 108161"},"PeriodicalIF":3.5,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145557402","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}
引用次数: 0
Editorial: Special issue: Bioinspired nanomaterials: Controlling biofilm and virulence of microbial pathogens 社论:特刊:生物启发纳米材料:控制生物膜和微生物病原体的毒力。
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-11-18 DOI: 10.1016/j.micpath.2025.108197
Fazlurrahman Khan
{"title":"Editorial: Special issue: Bioinspired nanomaterials: Controlling biofilm and virulence of microbial pathogens","authors":"Fazlurrahman Khan","doi":"10.1016/j.micpath.2025.108197","DOIUrl":"10.1016/j.micpath.2025.108197","url":null,"abstract":"","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"210 ","pages":"Article 108197"},"PeriodicalIF":3.5,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145564692","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}
引用次数: 0
期刊
Microbial pathogenesis
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1