المؤلفون: Bo Zhang, Honglin Ren, Xiaoxu Wang, Cheng Han, Yuanyuan Jin, Xueyu Hu, Ruoran Shi, Chengwei Li, Yuzhu Wang, Yansong Li, Shiying Lu, Zengshan Liu, Pan Hu

المصدر: Frontiers in Microbiology, Vol 15 (2024)

مصطلحات موضوعية: Listeria monocytogenes, comparative genomics, pan-genomics, biodiversity, target genes, Microbiology, QR1-502

الوصف: As a common foodborne pathogen, infection with L. monocytogenes poses a significant threat to human life and health. The objective of this study was to employ comparative genomics to unveil the biodiversity and evolutionary characteristics of L. monocytogenes strains from different regions, screening for potential target genes and mining novel target genes, thus providing significant reference value for the specific molecular detection and therapeutic targets of L. monocytogenes strains. Pan-genomic analysis revealed that L. monocytogenes from different regions have open genomes, providing a solid genetic basis for adaptation to different environments. These strains contain numerous virulence genes that contribute to their high pathogenicity. They also exhibit relatively high resistance to phosphonic acid, glycopeptide, lincosamide, and peptide antibiotics. The results of mobile genetic elements indicate that, despite being located in different geographical locations, there is a certain degree of similarity in bacterial genome evolution and adaptation to specific environmental pressures. The potential target genes identified through pan-genomics are primarily associated with the fundamental life activities and infection invasion of L. monocytogenes, including known targets such as inlB, which can be utilized for molecular detection and therapeutic purposes. After screening a large number of potential target genes, we further screened them using hub gene selection methods to mining novel target genes. The present study employed eight different hub gene screening methods, ultimately identifying ten highly connected hub genes (bglF_1, davD, menE_1, tilS, dapX, iolC, gshAB, cysG, trpA, and hisC), which play crucial roles in the pathogenesis of L. monocytogenes. The results of pan-genomic analysis showed that L. monocytogenes from different regions exhibit high similarity in bacterial genome evolution. The PCR results demonstrated the excellent specificity of the bglF_1 and davD genes for L. monocytogenes. Therefore, the bglF_1 and davD genes hold promise as specific molecular detection and therapeutic targets for L. monocytogenes strains from different regions.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fmicb.2024.1424868/fullTest; https://doaj.org/toc/1664-302XTest

الوصول الحر: https://doaj.org/article/1a4984dc9b5143bea81ec378e5fb8752Test

المؤلفون: Zhigang Cao, Xiaoya Ling, Abdul Haseeb, Panpan Sun, Hua Zhang, Wei Yin, Kuohai Fan, Huizhen Yang, Zhenbiao Zhang, Jia Zhong, Yaogui Sun, Na Sun, Hongquan Li

المصدر: Frontiers in Microbiology, Vol 15 (2024)

مصطلحات موضوعية: Lactobacillus acidophilus, PCV2, Cap, Rep, non-target metabolomics, high-throughput molecular docking, Microbiology, QR1-502

الوصف: Our previous studies have revealed that L. acidophilus possesses inhibitory effects on PCV2 proliferation in vivo, although the underlying mechanisms remain elusive. Probiotics like L. acidophilus are known to exert antiviral through their metabolites. Therefore, in this study, non-targeted metabolomics was used to detect the changes in metabolites of L. acidophilus after 24 h of proliferation. Subsequently, high-throughput molecular docking was utilized to analyze the docking scores of these metabolites with PCV2 Cap and Rep, aiming to identify compounds with potential anti-PCV2 effects. The results demonstrated that 128 compounds such as Dl-lactate were significantly increased. The results of high-throughput molecular docking indicated that compounds such as ergocristine, and telmisartan formed complexes with Cap and Rep, suggesting their potential anti-PCV2 properties. Furthermore, compounds like vitamin C, exhibit pharmacological effects consistent with L. acidophilus adding credence to the idea that L. acidophilus may exert pharmacological effects through its metabolites. These results will provide a foundation for the study of L. acidophilus.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fmicb.2024.1416235/fullTest; https://doaj.org/toc/1664-302XTest

الوصول الحر: https://doaj.org/article/ffaac74ec7894ef6bacf4c5038ecb366Test

المؤلفون: Ying Bai, Osikowicz, Lynn M., Hojgaard, Andrias, Eisen, Rebecca J.

المصدر: Frontiers in Microbiology; 2023, p1-11, 11p

مصطلحات موضوعية: NUCLEOTIDE sequencing, BARTONELLA, POLYMERASE chain reaction, DNA primers, RATTUS norvegicus, GENETIC variation, DRUG target

مستخلص: The genus Bartonella includes a group of species that are associated with a wide range of mammalian species, including human. It is challenging to detect all Bartonella species using a single molecular target due to its high genetic diversity. To solve this issue, we developed a quadruplex PCR amplicon sequencing assay using next-generation sequencing (NGS) technology for the detection and differentiation of Bartonella species. Our objective was to obtain the specific sequences of a minimum of two of the four target genes as confirmation of the identity of a particular Bartonella species using the assay. Four pairs of primers targeting specific regions on gltA, groEL, rpoB, and ssrA were evaluated for their capability of differentiating Bartonella species individually and collectively by performing singular PCR amplicon sequencing and quadruplex PCR amplicon sequencing. Using the quadruplex PCR amplicon sequencing, 24 Bartonella reference species were tested, all of which were successfully differentiated by at least two targets. Bartonella species were accurately identified from the artificially mixed DNA templates developed to simulate coinfections. The limit of detection was determined to be 1 fg based on testing a series of 10-fold dilutions of DNA from the Bartonella species. Testing of high DNA concentrations of 19 non-Bartonella species showed high specificity with none of the non-Bartonella species misclassified as Bartonella. Finally, the assay was evaluated by testing DNA extracts fromfield-collected body lice (Pediculus humanus humanus) and Norway rats (Rattus norvegicus): Bartonella quintana was detected and confirmed by three targets in the lice and Bartonella tribocorum was detected and confirmed by two targets in the rats. These results demonstrated that Bartonella species could be accurately and rapidly detected and differentiated into different tissue types using the quadruplex sequencing assay. [ABSTRACT FROM AUTHOR]

: Copyright of Frontiers in Microbiology is the property of Frontiers Media S.A. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Bourhia, Mohammed, Shahab, Muhammad, Guojun Zheng, Bin Jardan, Yousef A., Sitotaw, Baye, Ouahmane, Lahcen, Khallouki, Farid

المصدر: Frontiers in Microbiology; 2023, p1-12, 12p

مصطلحات موضوعية: MOLECULAR docking, DRUG target, DRUG development, MOLECULAR dynamics

مستخلص: The disease-free existence of humans is constantly under attack by a variety of infections caused by a variety of organisms including bacteria. Notable among the bacteria is Staphylococcus aureus which is an etiological organism for infections including impetigo, folliculitis, and furuncles. The response of the human immune system against this disease is often neutralized by the production of a pigment called Staphyloxanthin (STX) via a series of reactions mediated by several enzymes. Among these enzymes, dehydrosqualene synthase, also known as CrtM, has emerged as a viable drug target due to its role in mediating the first step of the pathway. Consequently, this study employs molecular modeling approaches including molecular docking, quantum mechanical calculations, and molecular dynamics (MD) simulations among others to investigate the potential of napthyridine derivatives to serve as inhibitors of the CrtM. The results of the study revealed the high binding affinities of the compounds for the target as demonstrated by their docking scores, while further subjection to screening pipeline aimed at determining their fitness for development into drugs revealed just one compound namely 6-[[1-[(2-fluorophenyl) methyl]triazol-4-yl] methoxy]-4-oxo-1H-1,5-naphthyridine-3-carboxylic acid as the compound with good drug-like, pharmacokinetics, and toxicity properties profiles. A 100 ns-long MD simulation of the complexes formed after molecular docking revealed the stable interaction of the compound with the target. Ultimately, this study can be a promising outlet to discover a weapon to fight against clinically resistant bacteria, however, further experimental studies are suggested to carry out in the wet lab, pre-clinical, and clinical levels. [ABSTRACT FROM AUTHOR]

: Copyright of Frontiers in Microbiology is the property of Frontiers Media S.A. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Pin Lv, Ziyu Fang, Jiyu Guan, Lijun Lv, Mengshi Xu, Xingyuan Liu, Zhuomei Li, Yungang Lan, Zi Li, Huijun Lu, Deguang Song, Wenqi He, Feng Gao, Dacheng Wang, Kui Zhao

المصدر: Frontiers in Microbiology, Vol 15 (2024)

مصطلحات موضوعية: Orf virus, genistein, vRNAP, drug target, viral replication, Microbiology, QR1-502

الوصف: Orf virus (ORFV), a typical member of the genus Parapoxvirus, Poxvirus family, causes a contagious pustular dermatitis in sheep, goats, and humans. Poxviruses encode a multisubunit DNA-dependent RNA polymerase (vRNAP) that carries out viral gene expression in the host cytoplasm, which is a viral factor essential to poxvirus replication. Due to its vital role in viral life, vRNAP has emerged as one of the potential drug targets. In the present study, we investigated the antiviral effect of genistein against ORFV infection. We provided evidence that genistein exerted antiviral effect through blocking viral genome DNA transcription/replication and viral protein synthesis and reducing viral progeny, which were dosedependently decreased in genistein-treated cells. Furthermore, we identified that genistein interacted with the vRNAP RPO30 protein by CETSA, molecular modeling and Fluorescence quenching, a novel antiviral target for ORFV. By blocking vRNAP RPO30 protein using antibody against RPO30, we confirmed that the inhibitory effect exerted by genistein against ORFV infection is mediated through the interaction with RPO30. In conclusion, we demonstrate that genistein effectively inhibits ORFV transcription in host cells by targeting vRNAP RPO30, which might be a promising drug candidate against poxvirus infection.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fmicb.2024.1336490/fullTest; https://doaj.org/toc/1664-302XTest

الوصول الحر: https://doaj.org/article/10dd15900e484aa48c82f575da414acfTest

المؤلفون: Zhang Huangwei, Jin Peiyuan, Kong Yixuan, Yang Zhimin, Zhou Yuxin, Jung Geunhwa, Hu Jian

المصدر: Frontiers in Microbiology; 2023, p1-10, 10p

مصطلحات موضوعية: MULTIDRUG resistance, PROPICONAZOLE, DRUG target, FUNGICIDES, FUNGICIDE resistance, AGROSTIS

مستخلص: Emerging multidrug resistance (MDR) in Clarireedia spp. is a huge challenge to the management of dollar spot (DS) disease on turfgrass. Insight into the molecular basis of resistance mechanisms may help identify key molecular targets for developing novel effective chemicals. Previously, a MDR isolate (LT586) of C. jacksonii with significantly reduced sensitivities to propiconazole, boscalid, and iprodione, and a fungicide-sensitive isolate (LT15) of the same species were isolated from creeping bentgrass (Agrostis stolonifera L.). The present study aimed to further explore the molecular mechanisms of resistance by using genome-wide transcriptional analyses of the two isolates. A total of 619 and 475 differentially expressed genes (DEGs) were significantly down and upregulated in the MDR isolate LT586, compared with the sensitive isolate LT15 without fungicide treatment. Three hundreds and six and 153 DEGs showed significantly lower and higher expression in the MDR isolate LT586 than those in the sensitive isolate LT15, which were commonly induced by the three fungicides. Most of the 153 upregulated DEGs were xenobiotic detoxification-related genes and genes with transcriptional functions. Fifty and 17 upregulated DEGs were also commonly observed in HRI11 (a MDR isolate of the C. jacksonii) compared with the HRS10 (a fungicide-sensitive isolate of same species) from a previous study without and with the treatment of propiconazole, respectively. The reliability of RNA-seq data was further verified by qRT-PCR method using a few select potentially MDR-related genes. Results of this study indicated that there were multiple uncharacterized genes, possibly responsible for MDR phenotypes in Clarireedia spp., which may have important implications in understanding the molecular mechanisms underlying MDR resistance. [ABSTRACT FROM AUTHOR]

: Copyright of Frontiers in Microbiology is the property of Frontiers Media S.A. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Pengya Feng, Xia Xue, Ihtisham Bukhari, Chunjing Qiu, Yingying Li, Pengyuan Zheng, Yang Mi

المصدر: Frontiers in Microbiology, Vol 15 (2024)

مصطلحات موضوعية: cancer therapy, gut microbiota, microbiota tumor microenvironment, synthetic biology, therapeutic target, Microbiology, QR1-502

الوصف: The development of cancer is not just the growth and proliferation of a single transformed cell, but its tumor microenvironment (TME) also coevolves with it, which is primarily involved in tumor initiation, development, metastasis, and therapeutic responses. Recent years, TME has been emerged as a potential target for cancer diagnosis and treatment. However, the clinical efficacy of treatments targeting the TME, especially its specific components, remains insufficient. In parallel, the gut microbiome is an essential TME component that is crucial in cancer immunotherapy. Thus, assessing and constructing frameworks between the gut microbiota and the TME can significantly enhance the exploration of effective treatment strategies for various tumors. In this review the role of the gut microbiota in human cancers, including its function and relationship with various tumors was summarized. In addition, the interaction between the gut microbiota and the TME as well as its potential applications in cancer therapeutics was described. Furthermore, it was summarized that fecal microbiota transplantation, dietary adjustments, and synthetic biology to introduce gut microbiota-based medical technologies for cancer treatment. This review provides a comprehensive summary for uncovering the mechanism underlying the effects of the gut microbiota on the TME and lays a foundation for the development of personalized medicine in further studies.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fmicb.2024.1287077/fullTest; https://doaj.org/toc/1664-302XTest

الوصول الحر: https://doaj.org/article/4f65e1b867c840808d03a3195d7e3ad8Test

المؤلفون: Jean Chang, Fo-Ting Shen, Wei-An Lai, Chien-Sen Liao, Wen-Ching Chen

المصدر: Frontiers in Microbiology, Vol 14 (2023)

مصطلحات موضوعية: morpholine fungicide, neonicotinoid insecticide, non-target organisms, relative microbial abundance, ecological functions, Microbiology, QR1-502

الوصف: In Taiwan, the pesticides dimethomorph and imidacloprid are recommended for pest control in vineyards. Therefore, tank-mixing of these two pesticides is usually a routine practice before application. This study analyzed the influence of vineyard soil microbial flora under the recommended and high dosages (100 times the recommended dosage) of dimethomorph and imidacloprid. Individual and combined applications of pesticides were also tested through batches of soil incubation experiments. Four treatments—control (C), dimethomorph (DT), imidacloprid (IM), and mixed application of dimethomorph and imidacloprid (ID)—were used in the experimental design. From the soil metabolism, no significant reaction was observed after 2 months in the recommended dosage group, regardless of whether the pesticides were being applied individually or combined. For the high dosage, imidacloprid showed a higher effect than the co-exposure treatments, showing a possible prolonged effect after its repetitive application. From PCoA analysis, pesticide treatments altered the soil ecology after 2 months, and the effect of imidacloprid can be explicitly observed at high dosages. At the phylum level, Acidobacteria can indicate pesticide application around the recommended dosage. It was inhibited by ID on day 7 and was augmented by all pesticides on day 63. The effect of the recommended dosage of pesticide mixtures after 2 months of incubation was revealed in the minor families Gemmataceae and Pirellulaceae, while the high dosage treatments affected both the core and the minor families. Our findings verified the changes in the composition of microbial communities upon pesticide application, which would affect carbon, nitrogen, sulfur, phosphorous cycles, and contaminant removal ability within the vineyard.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fmicb.2023.1249167/fullTest; https://doaj.org/toc/1664-302XTest

الوصول الحر: https://doaj.org/article/fb974b676e3c42008e8987bdf5bfc69aTest

المؤلفون: Akash, Shopnil, Baeza, Javiera, Mahmood, Sajjat, Mukerjee, Nobendu, Subramaniyan, Vetriselvan, Islam, Md. Rezaul, Gupta, Gaurav, Rajakumari, Vinibha, Chinni, Suresh V., Ramachawolran, Gobinath, Saleh, Fayez M., Albadrani, Ghadeer M., Sayed, Amany A., Abdel-Daim, Mohamed M.

المصدر: Frontiers in Microbiology; 2023, p1-16, 16p

مصطلحات موضوعية: DRUG development, DRUG discovery, COMPUTATIONAL biology, DRUG target, DRUG design, EMERGING infectious diseases, P-glycoprotein, NUCLEOPROTEINS

مصطلحات جغرافية: AFRICA

الشركة/الكيان: UNITED States. Food & Drug Administration

مستخلص: The Lassa virus (LASV), an RNA virus prevalent in West and Central Africa, causes severe hemorrhagic fever with a high fatality rate. However, no FDA-approved treatments or vaccines exist. Two crucial proteins, LASV glycoprotein and nucleoprotein, play vital roles in pathogenesis and are potential therapeutic targets. As effective treatments for many emerging infections remain elusive, cutting-edge drug development approaches are essential, such as identifying molecular targets, screening lead molecules, and repurposing existing drugs. Bioinformatics and computational biology expedite drug discovery pipelines, using data science to identify targets, predict structures, and model interactions. These techniques also facilitate screening leads with optimal drug-like properties, reducing time, cost, and complexities associated with traditional drug development. Researchers have employed advanced computational drug design methods such as molecular docking, pharmacokinetics, drug-likeness, and molecular dynamics simulation to investigate evodiamine derivatives as potential LASV inhibitors. The results revealed remarkable binding affnities, with many outperforming standard compounds. Additionally, molecular active simulation data suggest stability when bound to target receptors. These promising findings indicate that evodiamine derivatives may offer superior pharmacokinetics and drug-likeness properties, serving as a valuable resource for professionals developing synthetic drugs to combat the Lassa virus. [ABSTRACT FROM AUTHOR]

: Copyright of Frontiers in Microbiology is the property of Frontiers Media S.A. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Fenghua Zhang, Dali Wang

المصدر: Frontiers in Microbiology; 2023, p1-16, 16p

مصطلحات موضوعية: MEMBRANE proteins, DRUG target, SHORT-chain fatty acids, PERIPHERAL nervous system, GUT microbiome

مستخلص: The gut microbiota varies dramatically among individuals, and changes over time within the same individual, due to diversities in genetic backgrounds, diet, nutrient supplementations and use of antibiotics. Up until now, studies on dysbiosis of microbiota have expanded to a wider range of diseases, with Akkermansia muciniphila at the cross spot of many of these diseases. A. muciniphila is a Gram-negative bacterium that produces short-chain fatty acids (SCFAs), and Amuc_1100 is one of its most highly expressed outer membrane proteins. This review aims to summarize current knowledge on correlations between A. muciniphila and involved neuropsychological diseases published in the last decade, with a focus on the potential of this bacterium and its outer membrane proteins as therapeutic targets for these diseases, on the basis of evidence accumulated from animal and clinical studies, as well as mechanisms of action from peripheral to central nervous system (CNS). [ABSTRACT FROM AUTHOR]

: Copyright of Frontiers in Microbiology is the property of Frontiers Media S.A. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)