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The effect of quaternary ammonium compounds (QACs) on quorum sensing and resistance of P. aeruginosa in clinical settings
IF 3.3 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-02-28 DOI: 10.1016/j.micpath.2025.107378
Khawla E. Alsamhary
Pseudomonas aeruginosa, a formidable opportunistic pathogen, is notorious for its ability to form biofilms and produce virulence factors that favor chronic infections, especially in cystic fibrosis patients. The misuse of disinfectants, combined with environmental leakage and biodegradation, has led to widespread exposure of microorganisms to sub-lethal concentrations of disinfectants, particularly quaternary ammonium compounds (QACs). This study investigates the interaction between QACs, specifically ethylbenzalkyl dimethyl ammonium chloride (EBAC), and the quorum sensing (QS) mechanisms governing P. aeruginosa behavior. The results demonstrate that exposure to sub-minimum inhibitory concentrations (sub-MICs) of EBAC not only enhances the biofilm-forming capability of P. aeruginosa isolates but also modulates the expression of crucial QS-regulated genes. Notably, the bacteria exhibit increased production of biofilm-associated virulence factors such as pyocyanin and elastase, and altered antibiotic susceptibility profiles, indicating a shift towards persistent infection phenotypes. These findings reveal that QAC exposure can significantly increase resistance to antibiotics and external stressors like hydrogen peroxide. These results emphasize the need to reassess the efficacy of QACs in clinical disinfection settings, particularly against P. aeruginosa infections, and highlight the potential for unintended consequences of their use regarding bacterial behavior and virulence. This study provides novel insights into the role of QACs in modulating QS-mediated virulence and antibiotic resistance, offering a new perspective on the risks associated with sub-lethal disinfectant exposure.
铜绿假单胞菌是一种可怕的机会性病原体,因其能够形成生物膜并产生有利于慢性感染的毒力因子而臭名昭著,尤其是在囊性纤维化患者中。消毒剂的滥用,加上环境泄漏和生物降解,导致微生物广泛接触亚致死浓度的消毒剂,特别是季铵化合物(QACs)。本研究调查了 QACs(特别是乙基苯烷基二甲基氯化铵(EBAC))与控制铜绿假单胞菌行为的法定量感应(QS)机制之间的相互作用。研究结果表明,暴露于亚最低抑制浓度(sub-MICs)的 EBAC 不仅能增强铜绿假单胞菌分离株的生物膜形成能力,还能调节关键 QS 调控基因的表达。值得注意的是,这些细菌显示出生物膜相关毒力因子(如脓氰蛋白和弹性蛋白酶)的产生增加,以及抗生素敏感性特征的改变,这表明它们正在向持续感染表型转变。这些研究结果表明,暴露于 QAC 可显著增加对抗生素和过氧化氢等外部应激源的耐药性。这些结果表明,有必要重新评估 QAC 在临床消毒环境中的功效,尤其是针对铜绿假单胞菌感染的功效,并强调了使用 QAC 可能会对细菌行为和毒力造成意想不到的后果。这项研究为QACs在调节QS介导的毒力和抗生素耐药性方面的作用提供了新的见解,为亚致死消毒剂暴露的相关风险提供了新的视角。
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引用次数: 0
Characterization of novel phages KPAФ1, KP149Ф1, and KP149Ф2 for lytic efficiency against clinical MDR Klebsiella pneumoniae infections
IF 3.3 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-02-28 DOI: 10.1016/j.micpath.2025.107440
Shraddha S. Dandekar , Sinta Thanikkal , Arti Londhe , Pankhudi Bhutada , Ujjayni Saha , Shubhankar Pawar , Rachel Samson , Mahesh Dharne , Sunil D. Saroj , Santosh Koratkar
Phage therapy offers a promising approach to the increasing antimicrobial resistance of Klebsiella pneumoniae. This study highlights three novel lytic bacteriophages—KPAФ1, KP149Ф1, and KP149Ф2— targeting multidrug-resistant (MDR) K. pneumoniae. These phages belong to the Myoviridae and Podoviridae family and demonstrate their efficacy and stability across a wide range of temperatures (up to 60°C) and pH levels (pH 4 to 11). Genomic analysis reveals that they are free from virulence, toxicity, and antimicrobial resistance genes, making them promising candidates for therapeutic use. Among these phages, KPAФ1 showed the highest lytic activity with a 26.15% lysis against MDR K. pneumoniae isolates. Additionally, a phage cocktail comprising all three phages improved lytic efficacy to 32.30%. This study also examined the antimicrobial resistance profiles of K. pneumoniae isolates, emphasizing the critical need for alternative treatments. By effectively targeting resistant strains, these phages offer a potential candidacy to be used as a viable alternative or a complementary antimicrobial agent to traditional antibiotics, opening up the possibility for advanced phage-based therapies. The promising results from this study pave the way for developing new treatments that could significantly improve patient care and outcomes from the growing issue of resistant bacterial infections.
噬菌体疗法为解决肺炎克雷伯氏菌抗药性不断增加的问题提供了一种前景广阔的方法。本研究重点介绍了三种新型溶菌噬菌体--KPAФ1、KP149Ф1和KP149Ф2--针对耐多药(MDR)肺炎克雷伯菌的治疗方法。这些噬菌体属于肌病毒科(Myoviridae)和荚膜病毒科(Podoviridae),在很宽的温度范围(高达 60°C)和 pH 值范围(pH 值为 4 至 11)内都显示出了它们的有效性和稳定性。基因组分析表明,它们没有毒力、毒性和抗菌药耐药性基因,因此很有希望用于治疗。在这些噬菌体中,KPAФ1 的溶菌活性最高,对 MDR 肺炎克氏菌分离株的溶菌率为 26.15%。此外,由这三种噬菌体组成的噬菌体鸡尾酒将溶菌效率提高到了 32.30%。这项研究还考察了肺炎克氏菌分离株的抗菌药耐药性情况,强调了替代治疗的迫切需要。这些噬菌体能有效靶向耐药菌株,有望成为传统抗生素的可行替代品或补充抗菌剂,为基于噬菌体的先进疗法提供了可能。这项研究取得的令人鼓舞的成果为开发新的治疗方法铺平了道路,这些新疗法可以大大改善病人护理和治疗效果,解决日益严重的耐药性细菌感染问题。
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引用次数: 0
Antileishmanial activity of Ptilostemon chamaepeuce subsp. cyprius
IF 3.3 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-02-28 DOI: 10.1016/j.micpath.2025.107441
Chad Schou , Justus Mukavi , Jandirk Sendker , Androulla Miliotou , Vasiliki Christodoulou , Yiannis Sarigiannis , Aleksandar Jovanovic , Thomas J. Schmidt , Panagiotis Karanis
<div><h3>Background</h3><div>Phytochemicals from unexplored plant species may be vital to unlocking pharmaceutical antibiotic and antiparasitic discoveries. New compounds need to be discovered to combat antimicrobial resistance. This study aimed to investigate ethanolic leaf extracts from five endemic and four indigenous plants from Cyprus for antibacterial, antileishmanial, and antioxidant activities.</div></div><div><h3>Methods</h3><div>Ethanolic leaf extracts were screened for antibacterial activity using a broth microdilution assay and iodonitrotetrazolium chloride (INT) as a colourimetric redox indicator for determining the minimum inhibitory concentration (MIC) against four Gram-positive and two Gram-negative American Type Culture Collection (ATCC) reference bacteria. Total phenolic content (TPC), total flavonoid content (TFC) and radical scavenging activity assays were performed to screen for antioxidant potential. <em>Leishmania infantum</em> clinical culture (MCAN/CY/2005/CD57) was used to screen the extracts for <em>in vitro</em> antileishmanial activity. Their cytotoxicity <em>in vitro</em> was assessed using the resazurin fluorometric assay with a HepG2 cell line. As an estimate of <em>in vitro</em> toxicity, a brine shrimp lethality assay was performed.</div></div><div><h3>Results</h3><div>The ethanol extract of <em>Ptilostemon chamaepeuce</em> subsp. <em>cyprius</em> (Greuter) Chrtek & B. Slavik demonstrated antibacterial activity against <em>Enterococcus faecalis</em> (ATCC 29212) with minimum inhibitory concentration (MIC) < 0.625 mg/mL and antileishmanial activity against a clinical isolate of <em>L</em><em>.</em> <em>infantum</em> (MCAN/CY/2005/CD57) from an infected dog (promastigote IC<sub>50</sub> of 105.7 ± 2.5 μg/mL and amastigote IC<sub>50</sub> of 118.5 ± 4.3 μg/mL) after 48 h and compared to the activity of the reference drug, miltefosine (IC<sub>50</sub> of 3.7 ± 0.1 μg/mL and 18.5 ± 2.3 μg/mL, respectively). Liquid-chromatography-mass spectrometry (LC-MS) analysis revealed the presence of at least five sesquiterpene lactones (STLs) in <em>P. cham</em>. subsp. <em>cyprius</em> ethanolic extract. The main compound, deacylcynaropicrin, based on its high-resolution mass spectrum, is believed to be primarily responsible for the antileishmanial activity observed <em>in vitro</em>.</div><div><em>Quercus alnifolia</em> Poech ethanolic extract showed antibacterial activity against four Gram-positive and one Gram-negative bacteria with MIC values of < 0.625 mg/mL, respectively, and antioxidant capacity in DPPH radical scavenging assay with IC<sub>50</sub> of 0.155 ± 0.002 mg/mL and compared to ascorbic acid (IC<sub>50</sub> of 0.036 ± 0.000 mg/mL) and Trolox (IC<sub>50</sub> of 0.047 ± 0.001 mg/mL).</div></div><div><h3>Conclusion</h3><div>The ethanolic extract of <em>Ptilostemon chamaepeuce</em> subsp. <em>cyprius</em> demonstrated dose-dependent antileishmanial activity. This is the first data report of <em>P</em><em>
背景:来自未开发植物物种的植物化学物质可能是发现药物抗生素和抗寄生虫药物的关键。需要发现新的化合物来对抗抗菌药耐药性。本研究旨在调查塞浦路斯五种特有植物和四种本地植物乙醇叶提取物的抗菌、抗利什曼病和抗氧化活性:采用肉汤微量稀释法和碘硝基氯化四氮唑(INT)作为比色氧化还原指示剂筛选乙醇叶提取物的抗菌活性,以确定其对四种革兰氏阳性和两种革兰氏阴性美国类型培养物收集中心(ATCC)参考细菌的最小抑菌浓度(MIC)。总酚含量(TPC)、总黄酮含量(TFC)和自由基清除活性测定用于筛选抗氧化潜力。婴儿利什曼原虫临床培养物(MCAN/CY/2005/CD57)用于筛选提取物的体外抗利什曼活性。在 HepG2 细胞系中,使用利马苏林荧光测定法评估了这些提取物的体外细胞毒性。为了评估体外毒性,还进行了卤虫致死试验:结果:Ptilostemon chamaepeuce subsp. cyprius (Greuter) Chrtek & B. Slavik 的乙醇提取物对粪肠球菌(ATCC 29212)具有抗菌活性,最低抑菌浓度(MIC)为 105.7±2.5 μg/mL,母细胞 IC50 为 118.5±4.3 μg/mL),并与参考药物米替福新(IC50 分别为 3.7±0.1 μg/mL 和 18.5±2.3 μg/mL)的活性进行了比较。液相色谱-质谱法(LC-MS)分析表明,P. cham.subsp.cyprius乙醇提取物中至少含有五种倍半萜内酯(STL)。根据其高分辨率质谱,主要化合物脱乙酰基炔诺酮被认为是体外观察到的抗利什曼活性的主要成分。Quercus alnifolia Poech 乙醇提取物对四种革兰氏阳性菌和一种革兰氏阴性菌具有抗菌活性,与抗坏血酸(IC50 为 0.036±0.000 mg/mL)和 Trolox(IC50 为 0.047±0.001 mg/mL)相比,其 MIC 值为 0.155±0.002 mg/mL:Ptilostemon chamaepeuce subsp.cyprius的乙醇提取物具有剂量依赖性抗利什曼病活性。这是 Ptilostemon chamaepeuce subsp. cyprius 和 Quercus alnifolia 乙醇提取物在初步研究中显示抗菌、抗利什曼病和抗氧化活性的首次数据报告。此外,这是第一份关于 P. cham.这些发现凸显了这些地方性植物作为开发针对革兰氏阳性细菌感染和利什曼病的新药来源的潜力,鼓励了进一步的药物研究。
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引用次数: 0
Whole genome sequencing and In silico analysis of the safety and probiotic features of Lacticaseibacillus paracasei FMT2 isolated from fecal microbiota transplantation (FMT) capsules
IF 3.3 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-02-28 DOI: 10.1016/j.micpath.2025.107405
Amani Sliti , Ryeong-Hui Kim , Dokyung Lee , Jae-Ho Shin
Lacticaseibacillus paracasei is widely used as a probiotic supplement and food additive in the medicinal and food industries. However, its application requires careful evaluation of safety traits associated with probiotic pathogenesis, including the transfer of antibiotic-resistance genes, the presence of virulence and pathogenicity factors, and the potential disruptions of the gut microbiome and immune system. In this study, we conducted whole genome sequencing (WGS) of L. paracasei FMT2 isolated from fecal microbiota transplantation (FMT) capsules and performed genome annotation to assess its probiotic and safety attributes. Our comparative genomic analysis assessed this novel strain's genetic attributes and functional diversity and unraveled its evolutionary relationships with other L. paracasei strains. The assembly yielded three contigs: one corresponding to the chromosome and two corresponding to plasmids. Genome annotation revealed the presence of 2838 DNA-coding sequences (CDS), 78 ribosomal RNAs (rRNAs), 60 transfer RNAs (tRNAs), three non-coding RNAs (ncRNAs), and 126 pseudogenes. The strain lacked antibiotic resistance genes and pathogenicity factors. Two intact prophages, one Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) region, and three antimicrobial peptide gene clusters were identified, highlighting the genomic stability and antimicrobial potential of the strain. Furthermore, genes linked to probiotic functions, such as mucosal colonization, stress resistance, and biofilm formation, were characterized. The pan-genome analysis identified 3358 orthologous clusters, including 1775 single-copy clusters, across all L. paracasei strains. Notably, L. paracasei FMT2 contained many unique singleton genes, potentially contributing to its distinctive probiotic properties. Our findings confirm the potential of L. paracasei FMT2 for food and therapeutic applications based on its probiotic profile and safety.
{"title":"Whole genome sequencing and In silico analysis of the safety and probiotic features of Lacticaseibacillus paracasei FMT2 isolated from fecal microbiota transplantation (FMT) capsules","authors":"Amani Sliti ,&nbsp;Ryeong-Hui Kim ,&nbsp;Dokyung Lee ,&nbsp;Jae-Ho Shin","doi":"10.1016/j.micpath.2025.107405","DOIUrl":"10.1016/j.micpath.2025.107405","url":null,"abstract":"<div><div><em>Lacticaseibacillus paracasei</em> is widely used as a probiotic supplement and food additive in the medicinal and food industries. However, its application requires careful evaluation of safety traits associated with probiotic pathogenesis, including the transfer of antibiotic-resistance genes, the presence of virulence and pathogenicity factors, and the potential disruptions of the gut microbiome and immune system. In this study, we conducted whole genome sequencing (WGS) of <em>L. paracasei</em> FMT2 isolated from fecal microbiota transplantation (FMT) capsules and performed genome annotation to assess its probiotic and safety attributes. Our comparative genomic analysis assessed this novel strain's genetic attributes and functional diversity and unraveled its evolutionary relationships with other <em>L. paracasei</em> strains. The assembly yielded three contigs: one corresponding to the chromosome and two corresponding to plasmids. Genome annotation revealed the presence of 2838 DNA-coding sequences (CDS), 78 ribosomal RNAs (rRNAs), 60 transfer RNAs (tRNAs), three non-coding RNAs (ncRNAs), and 126 pseudogenes. The strain lacked antibiotic resistance genes and pathogenicity factors. Two intact prophages, one Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) region, and three antimicrobial peptide gene clusters were identified, highlighting the genomic stability and antimicrobial potential of the strain. Furthermore, genes linked to probiotic functions, such as mucosal colonization, stress resistance, and biofilm formation, were characterized. The pan-genome analysis identified 3358 orthologous clusters, including 1775 single-copy clusters, across all <em>L. paracasei</em> strains. Notably, <em>L. paracasei</em> FMT2 contained many unique singleton genes, potentially contributing to its distinctive probiotic properties. Our findings confirm the potential of <em>L. paracasei</em> FMT2 for food and therapeutic applications based on its probiotic profile and safety.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"202 ","pages":"Article 107405"},"PeriodicalIF":3.3,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537387","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
Environmental transition navigates phenotype switching, affecting the virulence and multidrug-resistant profile of pathogenic Morganella morganii
IF 3.3 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-02-28 DOI: 10.1016/j.micpath.2025.107430
Vikash Kumar, Basanta Kumar Das, Suvra Roy, Souvik Dhar, Kampan Bisai, Anupam Adhikari, Angana Majumder, Asim Kumar Jana
The bacteria's ability to respond to environmental changes is critical for their survival. This allows them to form intricate communities, withstand stress, and initiate virulence responses in hosts during infection, a phenomenon known as phenotypic switching. In this study, we investigated the role of shaking conditions on phenotype switch in multidrug-resistant and pathogenic Morganella morganii both under in vitro and in vivo conditions. The results demonstrate that M. morganii grown in non-shaking conditions, possibly causing low fluid shear, developed floccules or cellular aggregates, and substantially increased biofilm formation. Meanwhile, the bacterium grown in shaking conditions was non-flocculated and produced less biofilm. This phenotype switch leads to a significant change in the protein secretome and multidrug resistance profile. In the non-shaking condition, M. morganii secretes two main proteins of ∼80 and ∼100 kDa and displays multiple antibiotic resistance (MAR) values of 0.39. In contrast, the bacterial cell in a shaking flask secreted one prominent protein of ∼50 kDa and exhibited a lower MAR value of 0.31. These observations correspond with a significant reduction in both in vitro and in vivo virulence of M. morganii grown in non-shaking conditions, namely haemolysin, swimming motility, histomorphological changes, and survival assay as compared to bacterial cells in a shaking flask displayed higher virulence in both in vitro and in vivo condition. Furthermore, non-shaking tube-grown cells have higher expression of saa, astA, ibeA, papC and papG genes as compared to cells grown in the shaking flask exhibiting higher expression of kpsMT K1, kpsMTK5”, stx1, ireA and cdt genes. Taking together, the study offers strong evidence supporting the presence of two phenotype forms in the multidrug-resistant and pathogenic M. morganii strain, showing differential phenotypes. Additionally, since water flow and movement are prevalent characteristics in aquaculture systems, they can exert fluid shear on the resident microbial communities. Therefore, our study could serve as a foundation for understanding the behavior of M. morganii in aquaculture settings and enable the possibility of monitoring and controlling this multidrug-resistant and pathogenic bacterium by steering phenotypes.
细菌应对环境变化的能力对其生存至关重要。这使它们能够形成复杂的群落,承受压力,并在感染过程中对宿主启动毒力反应,这种现象被称为表型转换。在本研究中,我们研究了在体外和体内条件下,摇动条件对耐多药摩根氏菌和致病摩根氏菌表型转换的作用。结果表明,在非摇动条件下生长的摩根氏菌(可能造成低流体剪切力)会形成絮状物或细胞聚集体,并显著增加生物膜的形成。与此同时,在振荡条件下生长的细菌没有絮状物,产生的生物膜也较少。这种表型转换导致蛋白质分泌组和多药耐药性特征发生了显著变化。在非振荡条件下,摩根氏菌分泌两种主要蛋白质,分别为 80 和 100 kDa,多重抗生素耐药性(MAR)值为 0.39。相比之下,摇瓶中的细菌细胞只分泌一种 50 kDa 的主要蛋白质,MAR 值较低,为 0.31。这些观察结果表明,与摇瓶中的细菌细胞相比,在非摇动条件下生长的摩根氏菌在体外和体内的毒力都明显降低,即溶血素、游动性、组织形态学变化和存活率测定在体外和体内都显示出较高的毒力。此外,与在振荡烧瓶中生长的细胞相比,在非振荡管中生长的细胞具有更高的 saa、astA、ibeA、papC 和 papG 基因表达量,而在振荡烧瓶中生长的细胞则具有更高的 kpsMT K1、kpsMT "K5"、stx1、ireA 和 cdt 基因表达量。总之,这项研究提供了强有力的证据,证明耐多药和致病的摩根氏菌菌株存在两种表型,表现出不同的表型。此外,由于水流和运动是水产养殖系统的普遍特征,它们会对常驻微生物群落产生流体剪切力。因此,我们的研究可作为了解水产养殖环境中 M. morganii 行为的基础,并可通过引导表型来监测和控制这种耐多药的致病细菌。
{"title":"Environmental transition navigates phenotype switching, affecting the virulence and multidrug-resistant profile of pathogenic Morganella morganii","authors":"Vikash Kumar,&nbsp;Basanta Kumar Das,&nbsp;Suvra Roy,&nbsp;Souvik Dhar,&nbsp;Kampan Bisai,&nbsp;Anupam Adhikari,&nbsp;Angana Majumder,&nbsp;Asim Kumar Jana","doi":"10.1016/j.micpath.2025.107430","DOIUrl":"10.1016/j.micpath.2025.107430","url":null,"abstract":"<div><div>The bacteria's ability to respond to environmental changes is critical for their survival. This allows them to form intricate communities, withstand stress, and initiate virulence responses in hosts during infection, a phenomenon known as phenotypic switching. In this study, we investigated the role of shaking conditions on phenotype switch in multidrug-resistant and pathogenic <em>Morganella morganii</em> both under <em>in vitro</em> and <em>in vivo</em> conditions. The results demonstrate that <em>M</em>. <em>morganii</em> grown in non-shaking conditions, possibly causing low fluid shear, developed floccules or cellular aggregates, and substantially increased biofilm formation. Meanwhile, the bacterium grown in shaking conditions was non-flocculated and produced less biofilm. This phenotype switch leads to a significant change in the protein secretome and multidrug resistance profile. In the non-shaking condition, <em>M. morganii</em> secretes two main proteins of ∼80 and ∼100 kDa and displays multiple antibiotic resistance (MAR) values of 0.39. In contrast, the bacterial cell in a shaking flask secreted one prominent protein of ∼50 kDa and exhibited a lower MAR value of 0.31. These observations correspond with a significant reduction in both <em>in vitro</em> and <em>in vivo</em> virulence of <em>M</em>. <em>morganii</em> grown in non-shaking conditions, namely haemolysin, swimming motility, histomorphological changes, and survival assay as compared to bacterial cells in a shaking flask displayed higher virulence in both <em>in vitro</em> and <em>in vivo</em> condition. Furthermore, non-shaking tube-grown cells have higher expression of <em>saa</em>, <em>astA</em>, <em>ibeA</em>, <em>papC</em> and <em>papG</em> genes as compared to cells grown in the shaking flask exhibiting higher expression of <em>kpsMT K</em>1, <em>kpsMT</em> “<em>K5</em>”, <em>stx</em><sub>1</sub>, <em>ireA</em> and <em>cdt</em> genes. Taking together, the study offers strong evidence supporting the presence of two phenotype forms in the multidrug-resistant and pathogenic <em>M</em>. <em>morganii</em> strain, showing differential phenotypes. Additionally, since water flow and movement are prevalent characteristics in aquaculture systems, they can exert fluid shear on the resident microbial communities. Therefore, our study could serve as a foundation for understanding the behavior of <em>M. morganii</em> in aquaculture settings and enable the possibility of monitoring and controlling this multidrug-resistant and pathogenic bacterium by steering phenotypes.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"202 ","pages":"Article 107430"},"PeriodicalIF":3.3,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537370","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
Endophytic bacteria of Gracilaria edulis in combating human bacterial pathogens by PPDHMP – A crude to single molecule product development approach
IF 3.3 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-02-28 DOI: 10.1016/j.micpath.2025.107431
Manas Manam, Sankalp Srivatsa, W. Jabez Osborne
Resistance in human bacterial pathogens and lack of novel antibiotic development has led to the need for new antibiotics. Therefore, the current study was focused on endophytic bacteria from Gracilaria edulis, an edible seaweed, capable of synthesizing novel bioactive compounds with potential applications in the inhibition of human pathogens. The endophyte, identified as Bacillus subtilis through 16S rRNA gene sequencing, exhibited significant antibacterial activity against bacterial human pathogens. Using GC-MS, FTIR and NMR the lead compound was identified as Pyrrolo[1,2-α] pyrazine-1,4-dione, hexahydro-3-(2-methylpropyl) (PPDHMP). Optimized media composition using glucose, proline and valine significantly enhanced the production of PPDHMP which was observed by the increase in zone of inhibition. Molecular docking of PPDHMP indicated a high binding affinity to beta-lactamase, suggesting its potential as a beta-lactamase inhibitor. PPDHMP exhibited cell wall inhibitory activity and ADMET analysis revealed promising pharmacokinetic and toxicity profiles indicating its potential for further evaluation as an oral antibiotic candidate. Phytotoxicity assessments and hemolytic assay confirmed the non-toxic nature of the metabolites produced. This research highlights the immense potential of marine endophytes in addressing the escalating issue of antibiotic resistance and paves the way for innovative solutions in antimicrobial therapy.
{"title":"Endophytic bacteria of Gracilaria edulis in combating human bacterial pathogens by PPDHMP – A crude to single molecule product development approach","authors":"Manas Manam,&nbsp;Sankalp Srivatsa,&nbsp;W. Jabez Osborne","doi":"10.1016/j.micpath.2025.107431","DOIUrl":"10.1016/j.micpath.2025.107431","url":null,"abstract":"<div><div>Resistance in human bacterial pathogens and lack of novel antibiotic development has led to the need for new antibiotics. Therefore, the current study was focused on endophytic bacteria from <em>Gracilaria edulis,</em> an edible seaweed, capable of synthesizing novel bioactive compounds with potential applications in the inhibition of human pathogens. The endophyte, identified as <em>Bacillus subtilis</em> through 16S rRNA gene sequencing, exhibited significant antibacterial activity against bacterial human pathogens. Using GC-MS, FTIR and NMR the lead compound was identified as Pyrrolo[1,2-α] pyrazine-1,4-dione, hexahydro-3-(2-methylpropyl) (PPDHMP). Optimized media composition using glucose, proline and valine significantly enhanced the production of PPDHMP which was observed by the increase in zone of inhibition. Molecular docking of PPDHMP indicated a high binding affinity to beta-lactamase, suggesting its potential as a beta-lactamase inhibitor. PPDHMP exhibited cell wall inhibitory activity and ADMET analysis revealed promising pharmacokinetic and toxicity profiles indicating its potential for further evaluation as an oral antibiotic candidate. Phytotoxicity assessments and hemolytic assay confirmed the non-toxic nature of the metabolites produced. This research highlights the immense potential of marine endophytes in addressing the escalating issue of antibiotic resistance and paves the way for innovative solutions in antimicrobial therapy.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"202 ","pages":"Article 107431"},"PeriodicalIF":3.3,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537368","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
Design and evaluation of potent multiepitope broad spectrum DNA and protein vaccine candidates against leptospirosis
IF 3.3 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-02-27 DOI: 10.1016/j.micpath.2025.107418
Anita Chauhan , Dhwani Jhala , Ritik Thumar , Kopal Kapoor , Aneri Joshi , Devanshi Gajjar , Sriram Seshadri , Satyamitra Shekh , Chaitanya Joshi , Amrutlal Patel
Leptospirosis is a widespread zoonotic disease that causes severe health complications with no approved vaccine which provide broad range protection. In this study, we have focused on LruC protein from the outer membrane of Leptospira spp. LruC protein has been considered as promising target for vaccine due to its immunogenicity and conservancy. We have identified total 13 conserved B-cell, CTL, and HTL epitopes from 22 different pathogenic Leptospira species and serovars, which were linked with 4 linkers and 3 adjuvants (HBHA, CTB, TLR4) to design 36 multiepitope vaccine constructs to study the effect of different components on vaccine effectiveness. The antigenicity, immunogenicity, and non-allergenicity of the constructs were confirmed through computational analyses. Physico-chemical properties, secondary structure, and tertiary models of the vaccine constructs were predicted and validated. Molecular docking studies were conducted with Toll-like receptors (TLR2, TLR4) to assess binding affinity, identifying three top vaccine candidates (HBHA-construct 6, CTB-construct 9, and TLR4-construct 12) for further investigation. Further, these candidates were successfully cloned into pVAX1 and pET30a vectors to prepare DNA and protein vaccines, respectively. Moreover, these multiepitope vaccines were tested in mice models to assess its immunogenicity. ELISA performed with antisera against vaccine antigen, as well as crude extract of pathogenic Leptospira species showed significant IgG responses, particularly in protein vaccines. Flow cytometry revealed increased IFN-γ producing CD4+ and CD8+ T cells, especially in the TLR4-adjuvanted vaccine groups. The microscopic agglutination test further confirmed the specificity of the antibody response to Leptospira serovars. Overall, this study demonstrates the potential of these multiepitope vaccine constructs in eliciting a robust immune response, laying the foundation for future challenge study and preclinical evaluation.
钩端螺旋体病是一种广泛传播的人畜共患疾病,会导致严重的健康并发症,但目前还没有获得批准的疫苗。在这项研究中,我们重点研究了钩端螺旋体外膜中的 LruC 蛋白。由于其免疫原性和保守性,LruC 蛋白被认为是有希望的疫苗靶点。我们从 22 种不同的致病钩端螺旋体和血清型中找出了 13 个保守的 B 细胞、CTL 和 HTL 表位,并将其与 4 种连接体和 3 种佐剂(HBHA、CTB、TLR4)连接,设计出 36 种多表位疫苗构建体,以研究不同成分对疫苗效果的影响。通过计算分析确认了构建体的抗原性、免疫原性和非过敏性。对疫苗构建体的理化性质、二级结构和三级模型进行了预测和验证。与 Toll 样受体(TLR2、TLR4)进行了分子对接研究,以评估结合亲和力,确定了三个顶级候选疫苗(HBHA-构建体 6、CTB-构建体 9 和 TLR4-构建体 12)供进一步研究。此外,这些候选疫苗被成功克隆到 pVAX1 和 pET30a 载体中,分别用于制备 DNA 疫苗和蛋白疫苗。此外,还在小鼠模型中测试了这些多位点疫苗,以评估其免疫原性。使用针对疫苗抗原的抗血清以及病原钩端螺旋体的粗提取物进行的 ELISA 检测显示,IgG 反应显著,尤其是在蛋白疫苗中。流式细胞术显示,产生 IFN-γ 的 CD4+ 和 CD8+ T 细胞增多,尤其是在 TLR4 佐剂疫苗组中。显微凝集试验进一步证实了针对钩端螺旋体血清的抗体反应的特异性。总之,这项研究证明了这些多位点疫苗构建物在激发强大免疫反应方面的潜力,为未来的挑战研究和临床前评估奠定了基础。
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引用次数: 0
Scutellaria baicalensis stem and leaf combat chicken-derived respiratory bacterial infection
IF 3.3 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-02-27 DOI: 10.1016/j.micpath.2025.107439
Xilin Wang , Shihai Wu , Ning Guo , Feike Yu , Xiaofeng Xu , Xinghai Wang , Xiaohan Yu , Xiaoye Liu , Hong Dong
The Chinese poultry industry has witnessed rapid development, with laying hens playing a pivotal role. However, the escalating demand has led to an exponential increase in the population of laying hens raised, resulting in emerging challenges. Particularly during bacterial infections, substantial losses can be incurred. Presently, most farms heavily rely on antibiotics for disease prevention and control. Although this approach has yielded positive outcomes, prolonged usage may lead to the emergence of drug-resistant strains and residues. Consequently, research on alternative drugs has been initiated due to antibiotic prohibition and growing pathogen resistance. Chinese herbal medicine holds significant prominence across various domains, including animal husbandry and disease treatment, owing to its traditional roots in China. Scutellaria baicalensis is a traditional Chinese medicine derived from the dried root of the labiatae family plant Scutellaria baicalensis that possesses bitter taste and cold properties while exhibiting effects such as heat clearance, dampness elimination, lung purification, fire expulsion and heat detoxification. The aboveground components of Scutellaria baicalensis encompass stems and leaves, which yield approximately three times more than their root counterparts as traditional Chinese medicine resources. Sculltllarla bactlalensls products have been successfully applied in animal husbandry with therapeutic effects against sore throat, respiratory diseases, and heat detoxification. Therefore, in pursuit of economic sustainability, this study aims at developing an extract from Scutellaria baicalensis stems and leaves for treating respiratory bacterial infections among laying hens. The findings indicate that this extract exhibits excellent therapeutic efficacy against respiratory diseases among laying hens by reducing inflammatory cell levels within their lungs.
{"title":"Scutellaria baicalensis stem and leaf combat chicken-derived respiratory bacterial infection","authors":"Xilin Wang ,&nbsp;Shihai Wu ,&nbsp;Ning Guo ,&nbsp;Feike Yu ,&nbsp;Xiaofeng Xu ,&nbsp;Xinghai Wang ,&nbsp;Xiaohan Yu ,&nbsp;Xiaoye Liu ,&nbsp;Hong Dong","doi":"10.1016/j.micpath.2025.107439","DOIUrl":"10.1016/j.micpath.2025.107439","url":null,"abstract":"<div><div>The Chinese poultry industry has witnessed rapid development, with laying hens playing a pivotal role. However, the escalating demand has led to an exponential increase in the population of laying hens raised, resulting in emerging challenges. Particularly during bacterial infections, substantial losses can be incurred. Presently, most farms heavily rely on antibiotics for disease prevention and control. Although this approach has yielded positive outcomes, prolonged usage may lead to the emergence of drug-resistant strains and residues. Consequently, research on alternative drugs has been initiated due to antibiotic prohibition and growing pathogen resistance. Chinese herbal medicine holds significant prominence across various domains, including animal husbandry and disease treatment, owing to its traditional roots in China. <em>Scutellaria baicalensis</em> is a traditional Chinese medicine derived from the dried root of the labiatae family plant <em>Scutellaria baicalensis</em> that possesses bitter taste and cold properties while exhibiting effects such as heat clearance, dampness elimination, lung purification, fire expulsion and heat detoxification. The aboveground components of <em>Scutellaria baicalensis</em> encompass stems and leaves, which yield approximately three times more than their root counterparts as traditional Chinese medicine resources. <em>Sculltllarla bactlalensls</em> products have been successfully applied in animal husbandry with therapeutic effects against sore throat, respiratory diseases, and heat detoxification. Therefore, in pursuit of economic sustainability, this study aims at developing an extract from <em>Scutellaria baicalensis</em> stems and leaves for treating respiratory bacterial infections among laying hens. The findings indicate that this extract exhibits excellent therapeutic efficacy against respiratory diseases among laying hens by reducing inflammatory cell levels within their lungs.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"202 ","pages":"Article 107439"},"PeriodicalIF":3.3,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143526615","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
TLR-4Ab and IFNγAb with exogenous IL-10 treated LPS induced mice shown differential inflammatory response upon RANKL-M-CSF stimulation in resident bone marrow cells
IF 3.3 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-02-27 DOI: 10.1016/j.micpath.2025.107416
Gopinath Mukherjee, Sharmistha Samanta, Biswadev Bishayi
The inflammatory response in bone tissue often triggered by LPS is a complex process. Since LPS through TLR4 and in presence of IFNγ activates osteoclast differentiation and bone resorption, therefore, suppression of osteoclastogenesis through inhibition of TLR4 vs IFNγ mediated inflammation could be a reasonable strategy for the treatment of inflammatory bone loss. Administration of anti-TLR4 (30 mg/kg) and anti-IFNγ antibodies (6.6 mg/kg) were utilized before LPS (5 mg/kg) challenge and subsequently mice were treated with mouse IL-10 (0.02 mg/kg). Then RBMCs were isolated from different groups of mice and stimulated (in vitro) with M-CSF (10 ng/ml) and RANKL (10 ng/ml) to induce bone marrow cell differentiation in presence of LPS (100 ng/ml). The involvement of RANKL and M-CSF in the regulation of bone inflammation underlines the intricate signaling pathways. Furthermore, the study sheds light on the potential therapeutic effects of exogenous IL-10 possibly through STAT3 signaling in the RBMCs. The use of antibodies against TLR4 and IFNγ, in conjugation with IL-10in LPS bone damage model, appears to downregulate the activation of NF-κB, and reduction of many pro-inflammatory cytokines regulating the inflammatory cascade in RBMC. This suggests a promising avenue for the development of treatments aimed at mitigating bone inflammation associated with bacterial infections. Therefore, inhibition of TLR4 and IFNγ could be explored as potential therapeutic agents against LPS induced bone loss.
通常由 LPS 引发的骨组织炎症反应是一个复杂的过程。由于 LPS 通过 TLR4 和 IFNγ 激活破骨细胞分化和骨吸收,因此,通过抑制 TLR4 和 IFNγ 介导的炎症抑制破骨细胞生成可能是治疗炎症性骨质流失的合理策略。在小鼠接受 LPS(5 毫克/千克)挑战之前,给小鼠注射抗 TLR4(30 毫克/千克)和抗 IFNγ 抗体(6.6 毫克/千克),然后用小鼠 IL-10(0.02 毫克/千克)治疗。RANKL和M-CSF参与了骨炎症的调控,这凸显了信号通路的复杂性。此外,该研究还揭示了外源性IL-10可能通过STAT3信号传导对RBMCs的潜在治疗作用。在 LPS 骨损伤模型中使用 TLR4 和 IFNγ 抗体与 IL-10 结合使用,似乎可以下调 NF-κB 的活化,并减少许多调节 RBMC 炎症级联的促炎细胞因子。因此,抑制 TLR4 和 IFNγ 可作为治疗 LPS 引起的骨质流失的潜在药物进行研究。
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引用次数: 0
Molecular epidemiology and antibiotic resistance profiling of Staphylococcus aureus isolates from camel mastitis
IF 3.3 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-02-26 DOI: 10.1016/j.micpath.2025.107435
Hamza Rasheed , Muhammad Ijaz , Arslan Ahmed , Muhammad Muddassir Ali
Mastitis is considered one of milk-producing animals' most widespread infectious diseases. The present study evaluated the prevalence of antibiotic-resistant isolates of Staphylococcus aureus (S. aureus) including methicillin-resistant S. aureus (MRSA), β-lactam-resistant S. aureus (BRSA), aminoglycoside-resistant S. aureus (ARSA), and tetracycline-resistant S. aureus (TRSA) from the udder of dromedary camels along with the associated risk factors and the antibiogram of resistant isolates. Phylogenetic analysis of antibiotic-resistant genes with NCBI sequences was performed to check their homology. A total of 384 milk samples were collected and subjected to standard microbiological procedures to isolate S. aureus. The results revealed that 177 milk samples were found positive for subclinical mastitis (SCM) out of which 101 milk samples were found positive for S. aureus. The molecular assay found the prevalence of MRSA, BRSA, ARSA, and TRSA as 48.51 %, 46.53 %, 42.57 %, and 39.60 % by targeting the mecA, blaZ, accA-aphD, and tetK genes respectively. The study isolates significant similarities to each other and to previously reported sequences from other countries that were found by in-silico analysis, indicating the possibility of pathogen transboundary transmission. This study also revealed potential risk factors that aid in the spread of mastitis in camels. Among various risk factors, the most significant were farm hygiene, physiological status of animals, type of mastitis, teat injury, use of teat dips, and milk leakage (p < 0.05). The antibiogram of antibiotic-resistant isolates of S. aureus revealed that the highest resistance was observed against penicillin followed by amoxicillin and oxytetracycline while levofloxacin was the most sensitive drug. This study highlights the high prevalence of antimicrobial-resistant S. aureus in camel mastitis. Identified risk factors provide valuable insights into management practices that contribute to disease occurrence, aiding in the development of targeted control strategies. Additionally, antimicrobial susceptibility findings offer guidance for optimizing treatment protocols to effectively manage S. aureus-induced mastitis in camels and mitigate the spread of antimicrobial resistance.
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引用次数: 0
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Microbial pathogenesis
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