Pub Date : 2024-08-20DOI: 10.1016/j.micpath.2024.106875
This study evaluated the probiotic properties, safety profile, and antioxidative and immune system-enhancing effects of Enterococcus faecium strains isolated from human infant feces. E. faecium KU22001, E. faecium KU22002, and E. faecium KU22005 exhibited potential probiotic properties; however, to eliminate concerns about toxin production and antibiotic resistance, the E. faecium strains were heat-treated prior to experimental usage. E. faecium KU22001 showed the highest antioxidant activity and lowest reactive oxygen species production among the three strains. The immune system-enhancing effects of heat-killed E. faecium strains were evaluated using a nitric oxide assay. E. faecium KU22001 induced an increase in the mRNA expression of inducible nitric oxide synthase, cyclooxygenase-2, and proinflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, and interleukin-6 in RAW 264.7 cells. Furthermore, E. faecium KU22001 activated the mitogen-activated protein kinase pathway, which was a key regulator of the immune system. These results demonstrate the potential use of E. faecium KU22001 as a multifunctional food material.
{"title":"Antioxidative and immunity-enhancing effects of heat-killed probiotic Enterococcus faecium KU22001 without toxin or antibiotic resistance","authors":"","doi":"10.1016/j.micpath.2024.106875","DOIUrl":"10.1016/j.micpath.2024.106875","url":null,"abstract":"<div><p>This study evaluated the probiotic properties, safety profile, and antioxidative and immune system-enhancing effects of <em>Enterococcus faecium</em> strains isolated from human infant feces. <em>E. faecium</em> KU22001, <em>E. faecium</em> KU22002, and <em>E. faecium</em> KU22005 exhibited potential probiotic properties; however, to eliminate concerns about toxin production and antibiotic resistance, the <em>E. faecium</em> strains were heat-treated prior to experimental usage. <em>E. faecium</em> KU22001 showed the highest antioxidant activity and lowest reactive oxygen species production among the three strains. The immune system-enhancing effects of heat-killed <em>E. faecium</em> strains were evaluated using a nitric oxide assay. <em>E. faecium</em> KU22001 induced an increase in the mRNA expression of inducible nitric oxide synthase, cyclooxygenase-2, and proinflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, and interleukin-6 in RAW 264.7 cells. Furthermore, <em>E. faecium</em> KU22001 activated the mitogen-activated protein kinase pathway, which was a key regulator of the immune system. These results demonstrate the potential use of <em>E. faecium</em> KU22001 as a multifunctional food material.</p></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036343","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}
Pub Date : 2024-08-20DOI: 10.1016/j.micpath.2024.106877
Background
Candida albicans is an opportunistic pathogen commonly found in human mucous membranes. In light of the escalating challenge posed by antibiotic resistance of C. albicans strains worldwide, it is an urgently necessary to explore alternative therapeutic options.
Objective
This study aims to assess the efficacy of two Cinnamaldehyde derivatives, 2-Cl Cinnamaldehyde (2-Cl CA) and 4-Cl Cinnamaldehyde (4-Cl CA), against C. albicans through both in vitro experiments and in vivo murine models and to evaluate their potential as new drug candidates for treating C. albicans.
Methods and results
The minimum inhibitory concentrations (MICs) of Cinnamaldehyde 2-Cl and 4-Cl benzene ring derivatives against C. albicans were 25 μg/mL. Time-killing experiments revealed that both Cinnamaldehyde derivatives exhibited fungicidal activity against C. albicans at concentrations of 5 MIC and 10 MIC. In the checkerboard experiment, 4-Cl CA did not show any antagonistic effect when combined with first-line antifungal drugs. Instead, it exhibited additive effects in combination with nystatin. Both 2-Cl and 4-Cl CA demonstrated inhibitory activity against C. albicans biofilm formation, especially at 8 MIC and 16 MIC concentrations. In C. albicans biofilm eradication experiments, although high drug concentrations of 2-Cl and 4-Cl CA were unable to eradicate the biofilm completely, they were still effective in killing C. albicans cells within the biofilm. Moreover, sub-inhibitory concentrations of 4-Cl CA (ranging from 5 to 20 μg/mL) significantly inhibited cell aggregation and hyphal formation. Furthermore, 4-Cl CA effectively inhibited intracellular C. albicans infection in macrophages. Lastly, the effectiveness of 4-Cl CA was evaluated in a mouse model of hematogenous disseminated candidiasis caused by C. albicans, which revealed that 4-Cl CA significantly reduced fungal burden and improved mouse survival compared to the untreated controls.
Conclusion
The 4-Cl CA exhibited inhibitory effects against C. albicans through both in vivo and in vitro models, demonstrating its therapeutic potential as a promising new drug candidate for treating drug-resistant candidiasis albicans.
背景:白色念珠菌是一种常见于人体粘膜的机会性病原体。鉴于全球范围内白色念珠菌菌株对抗生素的耐药性所带来的挑战不断升级,迫切需要探索其他治疗方案:本研究旨在通过体外实验和体内小鼠模型评估两种肉桂醛衍生物--2-氯肉桂醛(2-Cl CA)和 4-氯肉桂醛(4-Cl CA)对白僵菌的疗效,并评估它们作为治疗白僵菌新药候选物的潜力:肉桂醛 2-Cl 和 4-Cl 苯环衍生物对白茨球菌的最低抑制浓度(MICs)为 25 μg/mL。杀菌时间实验表明,肉桂醛衍生物在 5 MIC 和 10 MIC 浓度下对白僵菌都具有杀菌活性。在棋盘实验中,4-Cl CA 与一线抗真菌药物联用时未显示出任何拮抗作用。相反,它与硝司他丁合用时却显示出了相加效应。2-Cl 和 4-Cl CA 对白僵菌生物膜的形成都有抑制作用,尤其是在 8 MIC 和 16 MIC 浓度下。在消灭白僵菌生物膜的实验中,虽然高浓度的 2-Cl 和 4-Cl CA 无法完全消灭生物膜,但仍能有效杀死生物膜内的白僵菌细胞。此外,亚抑制浓度的 4-Cl CA(5 至 20 μg/mL)能显著抑制细胞聚集和菌丝形成。此外,4-Cl CA 还能有效抑制巨噬细胞内的白僵菌感染。最后,在由白念珠菌引起的血源性播散性念珠菌病小鼠模型中评估了 4-Cl CA 的有效性,结果显示,与未经处理的对照组相比,4-Cl CA 能明显减轻真菌负担,提高小鼠存活率:结论:4-Cl CA 在体内和体外模型中都表现出了对白念珠菌的抑制作用,证明了其作为治疗耐药白念珠菌的候选新药的治疗潜力。
{"title":"Antifungal activity of Cinnamaldehyde derivatives against fluconazole-resistant Candida albicans","authors":"","doi":"10.1016/j.micpath.2024.106877","DOIUrl":"10.1016/j.micpath.2024.106877","url":null,"abstract":"<div><h3>Background</h3><p><em>Candida albicans</em> is an opportunistic pathogen commonly found in human mucous membranes. In light of the escalating challenge posed by antibiotic resistance of <em>C. albicans</em> strains worldwide, it is an urgently necessary to explore alternative therapeutic options.</p></div><div><h3>Objective</h3><p>This study aims to assess the efficacy of two Cinnamaldehyde derivatives, 2-Cl Cinnamaldehyde (2-Cl CA) and 4-Cl Cinnamaldehyde (4-Cl CA), against <em>C. albicans</em> through both <em>in vitro</em> experiments and <em>in vivo</em> murine models and to evaluate their potential as new drug candidates for treating <em>C. albicans</em>.</p></div><div><h3>Methods and results</h3><p>The minimum inhibitory concentrations (MICs) of Cinnamaldehyde 2-Cl and 4-Cl benzene ring derivatives against <em>C. albicans</em> were 25 μg/mL. Time-killing experiments revealed that both Cinnamaldehyde derivatives exhibited fungicidal activity against <em>C. albicans</em> at concentrations of 5 MIC and 10 MIC. In the checkerboard experiment, 4-Cl CA did not show any antagonistic effect when combined with first-line antifungal drugs. Instead, it exhibited additive effects in combination with nystatin. Both 2-Cl and 4-Cl CA demonstrated inhibitory activity against <em>C. albicans</em> biofilm formation, especially at 8 MIC and 16 MIC concentrations. In <em>C. albicans</em> biofilm eradication experiments, although high drug concentrations of 2-Cl and 4-Cl CA were unable to eradicate the biofilm completely, they were still effective in killing <em>C. albicans</em> cells within the biofilm. Moreover, sub-inhibitory concentrations of 4-Cl CA (ranging from 5 to 20 μg/mL) significantly inhibited cell aggregation and hyphal formation. Furthermore, 4-Cl CA effectively inhibited intracellular <em>C. albicans</em> infection in macrophages. Lastly, the effectiveness of 4-Cl CA was evaluated in a mouse model of hematogenous disseminated candidiasis caused by <em>C. albicans</em>, which revealed that 4-Cl CA significantly reduced fungal burden and improved mouse survival compared to the untreated controls.</p></div><div><h3>Conclusion</h3><p>The 4-Cl CA exhibited inhibitory effects against <em>C. albicans</em> through both <em>in vivo</em> and <em>in vitro</em> models, demonstrating its therapeutic potential as a promising new drug candidate for treating drug-resistant candidiasis albicans.</p></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036342","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}
Pub Date : 2024-08-19DOI: 10.1016/j.micpath.2024.106867
Bacillus thuringiensis Berliner is recognized as a predominant bioinsecticide but its antifungal potential has been relatively underexplored. A novel B. thuringiensis strain NBAIR BtAr was isolated and morphologically characterized using light and scanning electron microscopy, revealing presence of bipyramidal, cuboidal, and spherical parasporal crystals. The crude form of lipopeptides was extracted from NBAIR BtAr and assessed for its antagonistic activity in vitro, and demonstrated 100 % inhibition of Sclerotium rolfsii Sacc. at a minimum inhibitory concentration of 50 μL of the crude lipopeptide extract per mL of potato dextrose agar. To identify the antagonistic genes responsible, we performed whole genome sequencing of NBAIR BtAr, revealing the presence of circular chromosome of 5,379,913 bp and 175,362 bp plasmid with 36.06 % guanine-cytosine content and 5814 protein-coding sequences. Average nucleotide identity and whole genome phylogenetic analysis delineated the NBAIR BtAr strain as konkukian serovar. Gene ontology analysis revealed associations of 1474, 1323, and 1833 genes with biological processes, molecular function, and cellular components, respectively. Antibiotics & secondary metabolite analysis shell analysis of the whole genome yielded secondary metabolites biosynthetic gene clusters with 100 %, 85 %, 40 %, and 35 % similarity for petrobactin, bacillibactin, fengycin, and paenilamicin, respectively. Also, novel biosynthetic gene clusters, along with antimicrobial genes, including zwittermicin A, chitinase, and phenazines, were identified. Moreover, the presence of eight bacteriophage sequences, 18 genomic islands, insertion sequences, and one CRISPR region indicated prior occurrences of genetic exchange and thus improved competitive fitness of the strain. Overall, the whole genome sequence of NBAIR BtAr is presented, with its taxonomic classification and critical genetic attributes that contribute to its strong antagonistic activity against S. rolfsii.
{"title":"Hybrid de novo whole genome assembly of lipopeptide producing novel Bacillus thuringiensis strain NBAIR BtAr exhibiting antagonistic activity against Sclerotium rolfsii","authors":"","doi":"10.1016/j.micpath.2024.106867","DOIUrl":"10.1016/j.micpath.2024.106867","url":null,"abstract":"<div><p><em>Bacillus thuringiensis</em> Berliner is recognized as a predominant bioinsecticide but its antifungal potential has been relatively underexplored. A novel <em>B</em>. <em>thuringiensis</em> strain NBAIR BtAr was isolated and morphologically characterized using light and scanning electron microscopy, revealing presence of bipyramidal, cuboidal, and spherical parasporal crystals. The crude form of lipopeptides was extracted from NBAIR BtAr and assessed for its antagonistic activity <em>in vitro</em>, and demonstrated 100 % inhibition of <em>Sclerotium rolfsii</em> Sacc. at a minimum inhibitory concentration of 50 μL of the crude lipopeptide extract per mL of potato dextrose agar. To identify the antagonistic genes responsible, we performed whole genome sequencing of NBAIR BtAr, revealing the presence of circular chromosome of 5,379,913 bp and 175,362 bp plasmid with 36.06 % guanine-cytosine content and 5814 protein-coding sequences. Average nucleotide identity and whole genome phylogenetic analysis delineated the NBAIR BtAr strain as <em>konkukian</em> serovar. Gene ontology analysis revealed associations of 1474, 1323, and 1833 genes with biological processes, molecular function, and cellular components, respectively. Antibiotics & secondary metabolite analysis shell analysis of the whole genome yielded secondary metabolites biosynthetic gene clusters with 100 %, 85 %, 40 %, and 35 % similarity for petrobactin, bacillibactin, fengycin, and paenilamicin, respectively. Also, novel biosynthetic gene clusters, along with antimicrobial genes, including zwittermicin A, chitinase, and phenazines, were identified. Moreover, the presence of eight bacteriophage sequences, 18 genomic islands, insertion sequences, and one CRISPR region indicated prior occurrences of genetic exchange and thus improved competitive fitness of the strain. Overall, the whole genome sequence of NBAIR BtAr is presented, with its taxonomic classification and critical genetic attributes that contribute to its strong antagonistic activity against <em>S. rolfsii</em>.</p></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142012080","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}
Pub Date : 2024-08-18DOI: 10.1016/j.micpath.2024.106871
The H9N2 avian influenza virus (AIV) is spreading worldwide. Presence of H9N2 virus tends to increase the chances of infection with other pathogens which can lead to more serious economic losses. In a previous study, a regulated delayed lysis Salmonella vector was used to deliver a DNA vaccine named pYL233 encoding M1 protein, mosaic HA protein and chicken GM-CSF adjuvant. To further increase its efficiency, chitosan as a natural adjuvant was applied in this study. The purified plasmid pYL233 was coated with chitosan to form a DNA containing nanoparticles (named CS233) by ionic gel method and immunized by intranasal boost immunization in birds primed by oral administration with Salmonella strain. The CS233 DNA nanoparticle has a particle size of about 150 nm, with an encapsulation efficiency of 93.2 ± 0.12 % which protected the DNA plasmid from DNase I digestion and could be stable for a period of time at 37°. After intranasal boost immunization, the CS233 immunized chickens elicited higher antibody response, elevated CD4+ T cells and CD8+ T cells activation and increased T-lymphocyte proliferation, as well as increased productions of IL-4 and IFN-γ. After challenge, chickens immunized with CS233 resulted in the lowest levels of pulmonary virus titer and viral shedding as compared to the other challenge groups. The results showed that the combination of intranasal immunization with chitosan-coated DNA vaccine and oral immunization with regulatory delayed lytic Salmonella strain could enhance the immune response and able to provide protection against H9N2 challenge.
H9N2 禽流感病毒(AIV)正在全球蔓延。H9N2 病毒的存在往往会增加感染其他病原体的机会,从而导致更严重的经济损失。在之前的一项研究中,使用了一种调控延迟裂解沙门氏菌载体来递送名为 pYL233 的 DNA 疫苗,该载体编码 M1 蛋白、镶嵌 HA 蛋白和鸡 GM-CSF 佐剂。为了进一步提高效率,本研究还使用了天然佐剂壳聚糖。用离子凝胶法将纯化的质粒 pYL233 包覆在壳聚糖上,形成含 DNA 的纳米颗粒(命名为 CS233),并对口服沙门氏菌株的禽类进行鼻内增免。CS233 DNA 纳米粒子的粒径约为 150 nm,封装效率为 93.2 ± 0.12%,可保护 DNA 质粒不被 DNase I 消化,并可在 37 度下稳定一段时间。经鼻内强化免疫后,CS233 免疫鸡产生了较高的抗体反应,CD4+ T 细胞和 CD8+ T 细胞活化程度提高,T 淋巴细胞增殖增加,IL-4 和 IFN-γ 的产生增加。挑战后,与其他挑战组相比,CS233 免疫鸡的肺病毒滴度和病毒脱落水平最低。结果表明,壳聚糖包被 DNA 疫苗鼻内免疫与调节性延迟裂解沙门氏菌株口服免疫相结合,可增强免疫应答,并能对 H9N2 病毒挑战提供保护。
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Pub Date : 2024-08-18DOI: 10.1016/j.micpath.2024.106870
Plants are a treasure trove of biological materials containing a wide range of potential phytochemicals that are target-specific, rapidly biodegradable, and environmentally friendly, with multiple medicinal effects. Unfortunately, the development of resistance to synthetic pesticides and antibiotics led to the discovery of new antibiotics, antioxidants, and biopesticides. This has also led to the creation of new medications that work very well. The current study aimed to prove that ornamental plants contain specialized active substances that are used in several biological processes. Mosquitoes, one of the deadliest animals on the planet, cause millions of fatalities each year by transmitting several human illnesses. Phytochemicals are possible biological agents for controlling pests that are harmful. The potential of leaf extracts of Bougainvillea glabra, Delonix regia, Lantana camara, and Platycladus orientalis against Culex pipiens and microbial agents was evaluated. Acetone extracts had more toxic effects against Cx. pipiens larvae (99.0–100 %, 72 h post-treatment), and the LC50 values were 142.8, 189.5, 95.4, and 71.1 ppm for B. glabra, D. regia, L. camara, and P. orientalis, respectively. Plant extracts tested in this study showed high insecticidal, antimicrobial, and antioxidant potential. GC-MS and HPLC analyses showed a higher number of terpenes, flavonoids, and phenolic compounds. The ADME analysis of element, caryophyllene oxide, caryophyllene, and copaene showed that they were similar to drugs and that they were better absorbed by the body and able to pass through the blood-brain barrier. Our results confirm the ability of ornamental plants to have promising larvicidal and antimicrobial activity and biotechnology.
植物是生物材料的宝库,蕴藏着大量潜在的植物化学物质,这些物质具有靶向特异性、可快速生物降解、环境友好和多种药用功效。不幸的是,由于对合成杀虫剂和抗生素产生抗药性,人们发现了新的抗生素、抗氧化剂和生物杀虫剂。这也导致了效果非常好的新药物的诞生。目前的研究旨在证明观赏植物含有专门的活性物质,可用于多种生物过程。蚊子是地球上最致命的动物之一,每年传播多种人类疾病,造成数百万人死亡。植物化学物质可能是控制有害害虫的生物制剂。研究人员评估了九重葛、Delonix regia、Lantana camara 和 Platycladus orientalis 的叶片提取物对库蚊和微生物制剂的潜力。丙酮萃取物对蜱螨幼虫的毒性更强(99.0-100%,处理后 72 小时),B. glabra、D. regia、L. camara 和 P. orientalis 的半数致死浓度分别为 142.8、189.5、95.4 和 71.1 ppm。本研究测试的植物提取物具有很高的杀虫、抗菌和抗氧化潜力。气相色谱-质谱(GC-MS)和高效液相色谱(HPLC)分析表明,萜类、黄酮类和酚类化合物的数量较多。元素、氧化叶黄素、叶黄素和 copaene 的 ADME 分析表明,它们与药物相似,能更好地被人体吸收,并能通过血脑屏障。我们的研究结果证实了观赏植物具有良好的杀幼虫和抗菌活性以及生物技术能力。
{"title":"Biological effects of Bougainvillea glabra, Delonix regia, Lantana camara, and Platycladus orientalis extracts and their possible metabolomics therapeutics against the West Nile virus vector, Culex pipiens (Diptera: Culicidae)","authors":"","doi":"10.1016/j.micpath.2024.106870","DOIUrl":"10.1016/j.micpath.2024.106870","url":null,"abstract":"<div><p>Plants are a treasure trove of biological materials containing a wide range of potential phytochemicals that are target-specific, rapidly biodegradable, and environmentally friendly, with multiple medicinal effects. Unfortunately, the development of resistance to synthetic pesticides and antibiotics led to the discovery of new antibiotics, antioxidants, and biopesticides. This has also led to the creation of new medications that work very well. The current study aimed to prove that ornamental plants contain specialized active substances that are used in several biological processes. Mosquitoes, one of the deadliest animals on the planet, cause millions of fatalities each year by transmitting several human illnesses. Phytochemicals are possible biological agents for controlling pests that are harmful. The potential of leaf extracts of <em>Bougainvillea glabra, Delonix regia, Lantana camara,</em> and <em>Platycladus orientalis</em> against <em>Culex pipiens</em> and microbial agents was evaluated. Acetone extracts had more toxic effects against <em>Cx. pipiens</em> larvae (99.0–100 %, 72 h post-treatment), and the LC<sub>50</sub> values were 142.8, 189.5, 95.4, and 71.1 ppm for <em>B. glabra, D. regia, L. camara,</em> and <em>P. orientalis</em>, respectively. Plant extracts tested in this study showed high insecticidal, antimicrobial, and antioxidant potential. GC-MS and HPLC analyses showed a higher number of terpenes, flavonoids, and phenolic compounds. The ADME analysis of element, caryophyllene oxide, caryophyllene, and copaene showed that they were similar to drugs and that they were better absorbed by the body and able to pass through the blood-brain barrier. Our results confirm the ability of ornamental plants to have promising larvicidal and antimicrobial activity and biotechnology.</p></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142009039","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}
Pub Date : 2024-08-17DOI: 10.1016/j.micpath.2024.106866
Hospital associated infections or healthcare associated infections (HAIs) are a major threat to healthcare and medical management, mostly because of their recalcitrant nature. The primary cause of these HAIs is bacterial associations, especially the interspecies interactions. In interspecies interactions, more than one species co-exists in a common platform of extracellular polymeric substances (EPS), establishing a strong interspecies crosstalk and thereby lead to the formation of mixed species biofilms. In this process, the internal microenvironment and the surrounding EPS matrix of the biofilms ensure the protection of the microorganisms and allow them to survive under antagonistic conditions. The communications between the biofilm members as well as the interactions between the bacterial cells and the matrix polymers, also aid in the rigidity of the biofilm structure and allow the microorganisms to evade both the host immune response and a wide range of anti-microbials. Therefore, to design a treatment protocol for HAIs is difficult and it has become a growing point of concern. This review therefore first aims to discuss the role of microenvironment, molecular structure, cell-cell communication, and metabolism of mixed species biofilms in manifestation of HAIs. In addition, we discuss the electrochemical properties of mixed-species biofilms and their mechanism in developing drug resistance. Then we focus on the most dreaded bacterial HAI including oral and gut multi-species infections, catheter-associated urinary tract infections, surgical site infections, and ventilator-associated pneumonia. Further, we highlight the challenges to eradication of the mixed species biofilms and the current and prospective future strategies for the treatment of mixed species-associated HAI. Together, the review presents a comprehensive understanding of mixed species biofilm-mediated infections in clinical scenario, and summarizes the current challenge and prospect of therapeutic strategies against HAI.
医院相关感染或医疗相关感染(HAIs)是医疗保健和医疗管理的一大威胁,主要是因为它们具有顽固性。造成这些 HAIs 的主要原因是细菌关联,尤其是种间相互作用。在种间相互作用中,一个以上的物种共存于细胞外聚合物质(EPS)的共同平台上,形成强烈的种间串扰,从而导致混合物种生物膜的形成。在这一过程中,生物膜的内部微环境和周围的 EPS 基质确保了对微生物的保护,使它们能够在拮抗条件下生存。生物膜成员之间的交流以及细菌细胞和基质聚合物之间的相互作用也有助于生物膜结构的稳固,使微生物能够躲避宿主的免疫反应和各种抗微生物剂。因此,设计 HAIs 的治疗方案十分困难,这已成为人们日益关注的问题。因此,本综述首先旨在讨论混合物种生物膜的微环境、分子结构、细胞间通讯和新陈代谢在 HAIs 表现中的作用。此外,我们还讨论了混合菌种生物膜的电化学特性及其产生耐药性的机制。然后,我们重点讨论最可怕的细菌性 HAI,包括口腔和肠道多菌种感染、导管相关性尿路感染、手术部位感染和呼吸机相关性肺炎。此外,我们还强调了根除混合菌种生物膜所面临的挑战,以及治疗混合菌种相关 HAI 的当前和未来策略。综上所述,这篇综述全面介绍了临床上由混合菌种生物膜介导的感染,并总结了当前面临的挑战和针对 HAI 的治疗策略的前景。
{"title":"Mixed species biofilm: Structure, challenge and its intricate involvement in hospital associated infections","authors":"","doi":"10.1016/j.micpath.2024.106866","DOIUrl":"10.1016/j.micpath.2024.106866","url":null,"abstract":"<div><p>Hospital associated infections or healthcare associated infections (HAIs) are a major threat to healthcare and medical management, mostly because of their recalcitrant nature. The primary cause of these HAIs is bacterial associations, especially the interspecies interactions. In interspecies interactions, more than one species co-exists in a common platform of extracellular polymeric substances (EPS), establishing a strong interspecies crosstalk and thereby lead to the formation of mixed species biofilms. In this process, the internal microenvironment and the surrounding EPS matrix of the biofilms ensure the protection of the microorganisms and allow them to survive under antagonistic conditions. The communications between the biofilm members as well as the interactions between the bacterial cells and the matrix polymers, also aid in the rigidity of the biofilm structure and allow the microorganisms to evade both the host immune response and a wide range of anti-microbials. Therefore, to design a treatment protocol for HAIs is difficult and it has become a growing point of concern. This review therefore first aims to discuss the role of microenvironment, molecular structure, cell-cell communication, and metabolism of mixed species biofilms in manifestation of HAIs. In addition, we discuss the electrochemical properties of mixed-species biofilms and their mechanism in developing drug resistance. Then we focus on the most dreaded bacterial HAI including oral and gut multi-species infections, catheter-associated urinary tract infections, surgical site infections, and ventilator-associated pneumonia. Further, we highlight the challenges to eradication of the mixed species biofilms and the current and prospective future strategies for the treatment of mixed species-associated HAI. Together, the review presents a comprehensive understanding of mixed species biofilm-mediated infections in clinical scenario, and summarizes the current challenge and prospect of therapeutic strategies against HAI.</p></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142004597","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}
Pub Date : 2024-08-17DOI: 10.1016/j.micpath.2024.106863
Staphylococcus aureus is a bacterial pathogen that causes bloodstream infections, pneumonia, and skin abscesses and is the primary pathogen responsible for medical devices associated with biofilm infections, accounting for approximately 70 % of cases. Therefore, the World Health Organization (WHO) has designated this microorganism as a top priority due to its role in causing over 20,000 bacteremia-related deaths in the US each year. The issue of pathogen resistance to antibiotics, mainly by a biofilm, further complicates these infections since biofilms render the bacterial colony impervious to antibiotics. However, many natural and synthetic substances also induce bacterial biofilm formation. Therefore, we investigated whether the most common active pharmaceutical ingredients (APIs) could induce biofilm formation in two clinical isolates of extended-spectrum beta-lactamase Staphylococcus aureus, one of them also methicillin-resistant (A2M) and two medical devices.
We detected biofilm inducers, inhibitors, and destabilizers. Microbial strain, medical devices, API structure, and concentration influenced the modulatory effects of biofilm. In all devices tested, including microplates, FR18 duodenal probe, and respiratory probe, the clinic isolate methicillin-resistant S. aureus A2M exhibited lower susceptibility to biofilm formation than S. aureus A1. The anti-inflammatory acetaminophen, the hypocholesterolemic lovastatin, and the diuretic hydrochlorothiazide all induced biofilm. However, verapamil, an antihypertensive, and cetirizine, an antihistamine, inhibited biofilm on S. aureus A2M, while propranolol, another antihypertensive, inhibited biofilm on S. aureus A1. Additionally, diclofenac, an analgesic, and cetirizine destabilized the biofilm, resulting in more free bacteria and possibly making them more susceptible to external agents such as antibiotics. Nonetheless, further epidemiologic analyses and in vivo assays are needed to confirm these findings and to establish a correlation between drug use, the onset of bacterial infections in patients, and the use of medical devices.
This work provides information about the probable clinical implications of drugs in patients using medical devices or undergoing surgical procedures. Inhibitory APIs could also be used as drug repurposing or templates to design new, more potent biofilm inhibitors.
{"title":"Induction of biofilm in extended-spectrum beta-lactamase Staphylococcus aureus with drugs commonly used in pharmacotherapy","authors":"","doi":"10.1016/j.micpath.2024.106863","DOIUrl":"10.1016/j.micpath.2024.106863","url":null,"abstract":"<div><p><em>Staphylococcus aureus</em> is a bacterial pathogen that causes bloodstream infections, pneumonia, and skin abscesses and is the primary pathogen responsible for medical devices associated with biofilm infections, accounting for approximately 70 % of cases. Therefore, the World Health Organization (WHO) has designated this microorganism as a top priority due to its role in causing over 20,000 bacteremia-related deaths in the US each year. The issue of pathogen resistance to antibiotics, mainly by a biofilm, further complicates these infections since biofilms render the bacterial colony impervious to antibiotics. However, many natural and synthetic substances also induce bacterial biofilm formation. Therefore, we investigated whether the most common active pharmaceutical ingredients (APIs) could induce biofilm formation in two clinical isolates of extended-spectrum beta-lactamase <em>Staphylococcus aureus,</em> one of them also methicillin-resistant (A2M) and two medical devices.</p><p>We detected biofilm inducers, inhibitors, and destabilizers. Microbial strain, medical devices, API structure, and concentration influenced the modulatory effects of biofilm. In all devices tested, including microplates, FR18 duodenal probe, and respiratory probe, the clinic isolate methicillin-resistant <em>S. aureus</em> A2M exhibited lower susceptibility to biofilm formation than <em>S. aureus</em> A1. The anti-inflammatory acetaminophen, the hypocholesterolemic lovastatin, and the diuretic hydrochlorothiazide all induced biofilm. However, verapamil, an antihypertensive, and cetirizine, an antihistamine, inhibited biofilm on <em>S. aureus</em> A2M, while propranolol, another antihypertensive, inhibited biofilm on <em>S. aureus</em> A1. Additionally, diclofenac, an analgesic, and cetirizine destabilized the biofilm, resulting in more free bacteria and possibly making them more susceptible to external agents such as antibiotics. Nonetheless, further epidemiologic analyses and <em>in vivo</em> assays are needed to confirm these findings and to establish a correlation between drug use, the onset of bacterial infections in patients, and the use of medical devices.</p><p>This work provides information about the probable clinical implications of drugs in patients using medical devices or undergoing surgical procedures. Inhibitory APIs could also be used as drug repurposing or templates to design new, more potent biofilm inhibitors.</p></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0882401024003309/pdfft?md5=84e842cde7f831f4f9d016300754b34f&pid=1-s2.0-S0882401024003309-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142004596","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}
Staphylococcus aureus (S. aureus) is a kind of gram-positive bacteria, and its virulence factors can cause many kinds of infections. Traditional antibiotics can not only kill bacteria, but also easily lead to bacterial resistance. Jingfang Mixture (JFM) is commonly used in clinic to prevent and treat epidemic diseases and infectious diseases. The main purpose of this study is to explore the inhibitory effect of JFM on alpha-hemolysin (Hla) of S. aureus and to alleviate the damage caused by Hla. We found that JFM could inhibit the hemolytic activity, gene and protein level and neutralizing activity of Hla in a dose-dependent manner at the concentrations of 125, 250 and 500 μg/mL, without affecting the growth of bacteria. In addition, JFM reduced the damage of Hla to A549 cells and the release of lactate dehydrogenase (LDH). We also observed that in the S. aureus - induced pneumonia mouse model, JFM could significantly prolong the life of mice, reduce the bacterial load in the lungs, significantly improve the pathological state of the lungs and alleviate the damage caused by inflammatory factors, and the pathogenicity of gene deletion strain DU 1090 of S. aureus to pneumonia mice was also significantly reduced. In conclusion, this study proved that JFM is a potential drug against S. aureus infection, and this study provided a preliminary study for better guidance of clinical drug use.
{"title":"Inhibitory Effect of Jingfang Mixture on Staphylococcus aureus α-Hemolysin.","authors":"Wenting Ni, Fangjiao Wei, Chenghong Sun, Jingchun Yao, Xiaoping Zhang, Guimin Zhang","doi":"10.1016/j.micpath.2024.106840","DOIUrl":"https://doi.org/10.1016/j.micpath.2024.106840","url":null,"abstract":"<p><p>Staphylococcus aureus (S. aureus) is a kind of gram-positive bacteria, and its virulence factors can cause many kinds of infections. Traditional antibiotics can not only kill bacteria, but also easily lead to bacterial resistance. Jingfang Mixture (JFM) is commonly used in clinic to prevent and treat epidemic diseases and infectious diseases. The main purpose of this study is to explore the inhibitory effect of JFM on alpha-hemolysin (Hla) of S. aureus and to alleviate the damage caused by Hla. We found that JFM could inhibit the hemolytic activity, gene and protein level and neutralizing activity of Hla in a dose-dependent manner at the concentrations of 125, 250 and 500 μg/mL, without affecting the growth of bacteria. In addition, JFM reduced the damage of Hla to A549 cells and the release of lactate dehydrogenase (LDH). We also observed that in the S. aureus - induced pneumonia mouse model, JFM could significantly prolong the life of mice, reduce the bacterial load in the lungs, significantly improve the pathological state of the lungs and alleviate the damage caused by inflammatory factors, and the pathogenicity of gene deletion strain DU 1090 of S. aureus to pneumonia mice was also significantly reduced. In conclusion, this study proved that JFM is a potential drug against S. aureus infection, and this study provided a preliminary study for better guidance of clinical drug use.</p>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996173","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}
Pub Date : 2024-08-15DOI: 10.1016/j.micpath.2024.106864
The leaves of Piper betle L., known as betel leaf, have immense medicinal properties. It possesses potent antimicrobial efficacies and can be a valuable tool to combat drug-resistant microorganisms. Quorum sensing (QS) inhibition is one of the best strategies to combat drug resistance. The present study investigates the anti-quorum sensing and biofilm inhibitory potential of Piper betle L. leaf extract against two bacterial strains, Chromobacterium violaceum and Pseudomonas aeruginosa. The extract produced substantial QS-inhibition zones in a biosensor strain of C. violaceum (CV026), indicating interference with quorum-sensing signals. The Results demonstrated significant inhibition in biofilm formation and different QS-regulated virulence factors (violacein, exopolysaccharides, pyocyanin, pyoverdine, elastase) in both C. violaceum and P. aeruginosa at sub-MIC concentrations of the extract and tetracycline, an antibiotic with known anti-QS activity. The quantitative real-time PCR (qRT-PCR) revealed decreased gene expression in different QS-related genes in C. violaceum (cviI, cviR, and vioA) and P. aeruginosa (lasI, lasR, lasB, rhlI, rhlR, and rhlA) strains after treatment. Gas Chromatography-Mass Spectrometry (GC-MS) analysis identified the significant phytocompounds, mainly derivatives of chavicol and eugenol, in the extract. Of these compounds, chavicol acetate (affinity: −7.00 kcal/mol) and acetoxy chavicol acetate (affinity: −7.87 kcal/mol) showed the highest potential to bind with the CviR and LasR protein, respectively, as evident from the in-silico molecular docking experiment. The findings of this endeavour highlight the promising role of Piper betle L. as a source of natural compounds with anti-quorum sensing properties against pathogenic bacteria, opening avenues for developing novel therapeutic agents to combat bacterial infections.
{"title":"The anti-quorum sensing and biofilm inhibitory potential of Piper betle L. leaf extract and prediction of the roles of the potent phytocompounds","authors":"","doi":"10.1016/j.micpath.2024.106864","DOIUrl":"10.1016/j.micpath.2024.106864","url":null,"abstract":"<div><p>The leaves of <em>Piper betle</em> L., known as betel leaf, have immense medicinal properties. It possesses potent antimicrobial efficacies and can be a valuable tool to combat drug-resistant microorganisms. Quorum sensing (QS) inhibition is one of the best strategies to combat drug resistance. The present study investigates the anti-quorum sensing and biofilm inhibitory potential of <em>Piper betle</em> L. leaf extract against two bacterial strains, <em>Chromobacterium violaceum</em> and <em>Pseudomonas aeruginosa</em>. The extract produced substantial QS-inhibition zones in a biosensor strain of <em>C. violaceum</em> (CV026), indicating interference with quorum-sensing signals. The Results demonstrated significant inhibition in biofilm formation and different QS-regulated virulence factors (violacein, exopolysaccharides, pyocyanin, pyoverdine, elastase) in both <em>C. violaceum</em> and <em>P. aeruginosa</em> at sub-MIC concentrations of the extract and tetracycline, an antibiotic with known anti-QS activity. The quantitative real-time PCR (qRT-PCR) revealed decreased gene expression in different QS-related genes in <em>C. violaceum</em> (<em>cviI</em>, <em>cviR</em>, and <em>vioA</em>) and <em>P. aeruginosa</em> (<em>lasI</em>, <em>lasR</em>, <em>lasB</em>, <em>rhlI</em>, <em>rhlR</em>, and <em>rhlA</em>) strains after treatment. Gas Chromatography-Mass Spectrometry (GC-MS) analysis identified the significant phytocompounds, mainly derivatives of chavicol and eugenol, in the extract. Of these compounds, chavicol acetate (affinity: −7.00 kcal/mol) and acetoxy chavicol acetate (affinity: −7.87 kcal/mol) showed the highest potential to bind with the CviR and LasR protein, respectively, as evident from the <em>in-silico</em> molecular docking experiment. The findings of this endeavour highlight the promising role of <em>Piper betle</em> L. as a source of natural compounds with anti-quorum sensing properties against pathogenic bacteria, opening avenues for developing novel therapeutic agents to combat bacterial infections.</p></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996175","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}
Pub Date : 2024-08-15DOI: 10.1016/j.micpath.2024.106856
Biofilm formation is a major health concern and studies have been pursued to find compounds able to prevent biofilm establishment and remove pre-existing biofilms. While biosurfactants (BS) have been well-known for possessing antibiofilm activities, bioemulsifiers (BE) are still scarcely explored for this purpose. The present study aimed to evaluate the bioemulsifying properties of cell-free supernatants produced by Bacillaceae and Vibrio strains isolated from marine sponges and investigate their antiadhesive and antibiofilm activities against different pathogenic Gram-positive and Gram-negative bacteria. The BE production by the marine strains was confirmed by the emulsion test, drop-collapsing, oil-displacement, cell hydrophobicity and hemolysis assays. Notably, Bacillus cereus 64BHI1101 displayed remarkable emulsifying activity and the ultrastructure analysis of its BE extract (BE64-1) revealed the presence of structures typically observed in macromolecules composed of polysaccharides and proteins. BE64-1 showed notable antiadhesive and antibiofilm activities against Staphylococcus aureus, with a reduction of adherence of up to 100 % and a dispersion of biofilm of 80 %, without affecting its growth. BE64-1 also showed inhibition of Staphylococcus epidermidis and Escherichia coli biofilm formation and adhesion. Thus, this study provides a starting point for exploring the antiadhesive and antibiofilm activities of BE from sponge-associated bacteria, which could serve as a valuable tool for future research to combat S. aureus biofilms.
生物膜的形成是一个主要的健康问题,人们一直在研究如何找到能够防止生物膜形成和清除已有生物膜的化合物。众所周知,生物表面活性剂(BS)具有抗生物膜活性,但生物乳化剂(BE)在这方面的研究还很少。本研究旨在评估从海洋海绵中分离出的芽孢杆菌科(Bacillaceae)和弧菌科(Vibrio)菌株产生的无细胞上清液的生物乳化特性,并研究它们对不同致病性革兰氏阳性和革兰氏阴性细菌的抗粘附和抗生物膜活性。乳化试验、滴塌试验、油置换试验、细胞疏水性试验和溶血试验证实了海洋菌株产生的 BE。值得注意的是,蜡样芽孢杆菌 64BHI1101 具有显著的乳化活性,其 BE 提取物(BE64-1)的超微结构分析表明,BE64-1 具有在由多糖和蛋白质组成的大分子中观察到的典型结构。BE64-1 对金黄色葡萄球菌具有显著的抗粘附和抗生物膜活性,粘附力降低达 100%,生物膜分散达 80%,且不影响其生长。BE64-1 还能抑制表皮葡萄球菌和大肠杆菌生物膜的形成和粘附。因此,这项研究为探索海绵相关细菌中的 BE 的抗粘附和抗生物膜活性提供了一个起点,可作为未来研究抗击金黄色葡萄球菌生物膜的重要工具。
{"title":"Bioemulsifier from sponge-associated bacteria reduces staphylococcal biofilm","authors":"","doi":"10.1016/j.micpath.2024.106856","DOIUrl":"10.1016/j.micpath.2024.106856","url":null,"abstract":"<div><p>Biofilm formation is a major health concern and studies have been pursued to find compounds able to prevent biofilm establishment and remove pre-existing biofilms. While biosurfactants (BS) have been well-known for possessing antibiofilm activities, bioemulsifiers (BE) are still scarcely explored for this purpose. The present study aimed to evaluate the bioemulsifying properties of cell-free supernatants produced by Bacillaceae and <em>Vibrio</em> strains isolated from marine sponges and investigate their antiadhesive and antibiofilm activities against different pathogenic Gram-positive and Gram-negative bacteria. The BE production by the marine strains was confirmed by the emulsion test, drop-collapsing, oil-displacement, cell hydrophobicity and hemolysis assays. Notably, <em>Bacillus cereus</em> 64BHI1101 displayed remarkable emulsifying activity and the ultrastructure analysis of its BE extract (BE64-1) revealed the presence of structures typically observed in macromolecules composed of polysaccharides and proteins. BE64-1 showed notable antiadhesive and antibiofilm activities against <em>Staphylococcus aureus</em>, with a reduction of adherence of up to 100 % and a dispersion of biofilm of 80 %, without affecting its growth. BE64-1 also showed inhibition of <em>Staphylococcus epidermidis</em> and <em>Escherichia coli</em> biofilm formation and adhesion<em>.</em> Thus, this study provides a starting point for exploring the antiadhesive and antibiofilm activities of BE from sponge-associated bacteria, which could serve as a valuable tool for future research to combat <em>S. aureus</em> biofilms.</p></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996171","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}