Frontiers in Cellular and Infection Microbiology最新文献

{"title":"Head-to-head comparison of two human papillomavirus vaccines for efficacy against cervical intraepithelial neoplasia grade 3 and adenocarcinoma in situ—population-based follow-up of two cluster-randomized trials","authors":"Matti Lehtinen, Penelope Gray, Tapio Luostarinen, Tiina Eriksson, Dan Apter, Anne Bly, Katja Harjula, Kaisa Heikkilä, Mari Hokkanen, Marjo Kuortti, Pekka Nieminen, Mervi Nummela, Jorma Paavonen, Johanna Palmroth, Tiina Petäjä, Ville N. Pimenoff, Eero Pukkala, Joakim Dillner","doi":"10.3389/fcimb.2024.1437704","DOIUrl":"https://doi.org/10.3389/fcimb.2024.1437704","url":null,"abstract":"IntroductionWe report head-to-head comparison of the bivalent and quadrivalent HPV vaccine efficacies against immediate precursors of cervical cancer from 15 years’ country-wide cancer registry follow-up of phase III trial cohorts and an age-aligned cohort of unvaccinated women.MethodsThese individually and/or clusterrandomized cohorts of HPV6/11/16/18- and HPV16/18-vaccinated and unvaccinated women were enrolled, respectively, in 2002, 2004, and 2003/2005. The trial cohorts comprised initially 16- to 17-year-old HPV6/11/16/18-vaccinated FUTURE II (NCT00092534) participants (866) and HPV16/18-vaccinated PATRICIA (NCT00122681) and 012 trial (NCT00169494) participants (2,465), and 16,526 initially 16- to 19-year-old unvaccinated controls. After active 4-year clinical follow-up, passive, country-wide Finnish Cancer Registry (FCR) follow-up for cervical intraepithelial neoplasia grade 3 (CIN3) and adenocarcinoma in situ (AIS) was based on consented use of unique personal identifiers and started 6 months after the end of the FUTURE II and PATRICIA trials in 2007 and 2009, and ended at the end of 2019. The follow-up with altogether 229,020 follow-up years was age-aligned to ensure that similarly aged cohorts were passively followed up for 15 years post=vaccination for the intention-to-treat analyses of vaccine efficacy.ResultsOverall, we identified 5 and 16 CIN3 (no AIS) cases in the HPV6/11/16/18 and HPV16/18 cohorts, respectively, during the FCR-based follow-up. In the unvaccinated cohort, we identified 281 CIN3 cases, 20 AIS cases, and 13 cases with invasive cervical cancer. Vaccine efficacies against CIN3+ were 68.4% and 64.5% for the quadrivalent and the bivalent vaccines, respectively, with overlapping confidence intervals.DiscussionLong-term follow-up of randomized, initially adolescent HPV-vaccinated and unvaccinated cohorts shows, in this head-to-head setting, that the bivalent and quadrivalent HPV vaccines are equally effective against immediate precursors of cervical cancer.","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142198207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vaginal microbiota of pregnant women with Ureaplasma urealyticum and Mycoplasma hominis infections","authors":"Kwan Young Oh, Sunghee Lee, Jaewan Park, Mi Hye Park, Ji Hun Jeong, Jung Bo Yang, Chul Kwon Lim, Joong Gyu Ha, Yun Seok Yang","doi":"10.3389/fcimb.2024.1445300","DOIUrl":"https://doi.org/10.3389/fcimb.2024.1445300","url":null,"abstract":"BackgroundThe association between preterm birth and <jats:italic>Mycoplasma</jats:italic> species such as <jats:italic>Mycoplasma hominis</jats:italic> and <jats:italic>Ureaplasma urealyticum</jats:italic> has been extensively investigated. In a clinical setting, conventional diagnostic methods for them involve culture methods for <jats:italic>Mycoplasma</jats:italic> spp. and <jats:italic>Ureaplasma</jats:italic> spp., along with PCR tests. However, the clinical utility of these tests remains controversial, highlighting the necessity for more robust and reliable methods for identifying and understanding <jats:italic>Mycoplasma</jats:italic> infections.ObjectiveThis study aimed to assess the distribution of microbiota in pregnant women with <jats:italic>Mycoplasma hominis</jats:italic> and <jats:italic>Ureaplasma urealyticum</jats:italic> infection by the comparison of conventional diagnostic methods with vaginal microbial community analysis.Study DesignThis prospective case–control study involved 228 Korean pregnant women and utilized vaginal microbial community analysis, <jats:italic>Ureaplasma</jats:italic>/<jats:italic>Mycoplasma</jats:italic> culture, and 12-multiplex PCR for sexually transmitted diseases. Cross-correlation analysis in SPSS 27 compared the results of two conventional methods with vaginal microbial community analysis. R software generated box plots depicting the relative abundance of microorganisms. Network analysis was conducted using Cytoscape.ResultsPositive <jats:italic>Ureaplasma urealyticum</jats:italic> culture findings were observed in 60.2% of patients, with 76.4% positive for <jats:italic>Ureaplasma parvum</jats:italic> PCR and 13.2% positive for <jats:italic>Ureaplasma urealyticum</jats:italic> PCR. <jats:italic>Mycoplasma hominis</jats:italic> culture was positive only in two patients, while <jats:italic>Mycoplasma hominis</jats:italic> PCR was positive in eight women. Vaginal microbial community analysis identified significant differences in relative abundances of <jats:italic>Gardnerella species</jats:italic> type I and <jats:italic>Fannyhessea vaginae</jats:italic> between the <jats:italic>Ureaplasma urealyticum</jats:italic> PCR positive and negative groups. <jats:italic>Mycoplasma hominis</jats:italic> PCR positive patients exhibited significant differences in 11 bacterial species, including <jats:italic>Gardnerella species</jats:italic> I and <jats:italic>Fannyhessea vaginae</jats:italic>.ConclusionThis study suggests that STD-PCR may be more accurate than <jats:italic>Ureaplasma</jats:italic>/<jats:italic>Mycoplasma</jats:italic> culture for the diagnosis of <jats:italic>Mycoplasma hominis</jats:italic> and <jats:italic>Ureaplasma urealyticum</jats:italic> infection. Also, the presence of <jats:italic>Gardnerella species</jats:italic> I and <jats:italic>Fannyhessea vaginae</jats:italic> implies their potential influences on <jats:italic>Ureaplasma urealyticum</jats:italic> and <jats:italic>Mycoplasma homini","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142227796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human breast milk isolated lactic acid bacteria: antimicrobial and immunomodulatory activity on the Galleria mellonella burn wound model","authors":"Antonio Guarnieri, Noemi Venditti, Marco Alfio Cutuli, Natasha Brancazio, Giovanna Salvatore, Irene Magnifico, Laura Pietrangelo, Marilina Falcone, Franca Vergalito, Daria Nicolosi, Franco Scarsella, Sergio Davinelli, Giovanni Scapagnini, Giulio Petronio Petronio, Roberto Di Marco","doi":"10.3389/fcimb.2024.1428525","DOIUrl":"https://doi.org/10.3389/fcimb.2024.1428525","url":null,"abstract":"IntroductionManaging burn injuries is a challenge in healthcare. Due to the alarming increase in antibiotic resistance, new prophylactic and therapeutic strategies are being sought. This study aimed to evaluate the potential of live Lactic Acid Bacteria for managing burn infections, using <jats:italic>Galleria mellonella larvae</jats:italic> as an alternative preclinical animal model and comparing the outcomes with a common antibiotic.MethodsThe antimicrobial activity of LAB isolated from human breast milk was assessed <jats:italic>in vitro</jats:italic> against <jats:italic>Pseudomonas aeruginosa</jats:italic> ATCC 27853. Additionally, the immunomodulatory effects of LAB were evaluated <jats:italic>in vivo</jats:italic> using the <jats:italic>G. mellonella</jats:italic> burn wound infection model.Results and discussion<jats:italic>In vitro</jats:italic> results demonstrated the antimicrobial activity of Lactic Acid Bacteria against <jats:italic>P. aeruginosa</jats:italic>. <jats:italic>In vivo</jats:italic> results show that their prophylactic treatment improves, statistically significant, larval survival and modulates the expression of immunity-related genes, Gallerimycin and Relish/NF-κB, strain-dependently. These findings lay the foundation and suggest a promising alternative for burn wound prevention and management, reducing the risk of antibiotic resistance, enhancing immune modulation, and validating the potential <jats:italic>G. mellonella</jats:italic> as a skin burn wound model.","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142198008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic performance of metagenomic sequencing in patients with suspected infection: a large-scale retrospective study","authors":"Ziyang Li, Li Tan, Jialiang Zhang, Qichen Long, Zhiyang Chen, Zhongyuan Xiang, Weimin Wu, Zhe Guo, Huifang Liu, Bingxue Hu, Bin Yang, Min Hu","doi":"10.3389/fcimb.2024.1463081","DOIUrl":"https://doi.org/10.3389/fcimb.2024.1463081","url":null,"abstract":"BackgroundMetagenomic next-generation sequencing (mNGS) has been widely reported to identify pathogens in infectious diseases (IDs). In this work, we intended to investigate the diagnostic value and clinical acceptance of paired-samples mNGS as compared to the culture method.MethodsA total of 361 patients with suspected infection were retrospectively included. With reference to the clinical diagnosis, we compared the diagnostic performance and clinical acceptance in pathogen detection between mNGS and culture tests. Moreover, the pathogen concordance of paired blood and respiratory tract (RT) samples in mNGS assay was investigated.ResultsAmong 511 samples, 62.04% were shown to be pathogen positive by mNGS, and that for clinical diagnosis was 51.86% (265/511). When compared to culture assay (<jats:italic>n</jats:italic> = 428), mNGS had a significantly higher positivity rate (51.87% vs. 33.18%). With reference to the clinical diagnosis, the sensitivity of mNGS outperformed that of culture (89.08% vs. 56.72%). Importantly, mNGS exhibited a clinically accepted rate significantly superior to that of culture. In addition, the mNGS result from 53 paired blood and RT samples showed that most pairs were pathogen positive by both blood and RT, with pathogens largely being partially matched.ConclusionThrough this large-scale study, we further illustrated that mNGS had a clinically accepted rate and sensitivity superior to those of the traditional culture method in diagnosing infections. Moreover, blood and paired RT samples mostly shared partial-matched positive pathogens, especially for pathogens with abundant read numbers in RT, indicating that both blood and RT mNGS can aid the identification of pathogens for respiratory system infection.","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142198208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combining network pharmacology, machine learning, molecular docking and molecular dynamic to explore the mechanism of Chufeng Qingpi decoction in treating schistosomiasis","authors":"Minglu Liu, Yuxin Wang, Wen Deng, Jiahao Xie, Yanyao He, Liang Wang, Jianbin Zhang, Ming Cui","doi":"10.3389/fcimb.2024.1453529","DOIUrl":"https://doi.org/10.3389/fcimb.2024.1453529","url":null,"abstract":"BackgroundAlthough the Chufeng Qingpi Decoction (CQD) has demonstrated clinical effectiveness in the treatment of schistosomiasis, the precise active components and the underlying mechanisms of its therapeutic action remain elusive. To achieve a profound comprehension, we incorporate network pharmacology, bioinformatics analysis, molecular docking, and molecular dynamics simulations as investigative methodologies within our research framework.MethodUtilizing TCMSP and UniProt, we identified formula components and targets. Cytoscape 3.10.0 was used to construct an herb–target interaction network. Genecards, DisGeNET, and OMIM databases were examined for disease-related objectives. A Venn diagram identified the intersection of compound and disease targets. Using Draw Venn, overlapping targets populated STRING for PPI network. CytoNCA identified schistosomiasis treatment targets. GO &amp;amp; KEGG enrichment analysis followed High-scoring genes in PPI were analyzed by LASSO, RF, SVM-RFE. Molecular docking &amp;amp; simulations investigated target-compound interactions.ResultThe component’s target network encompassed 379 nodes, 1629 edges, highlighting compounds such as wogonin, kaempferol, luteolin, and quercetin. Amongst the proteins within the PPI network, PTGS2, TNF, TGFB1, BCL2, TP53, IL10, JUN, MMP2, IL1B, and MYC stood out as the most prevalent entities. GO and KEGG revealed that mainly involved the responses to UV, positive regulation of cell migration and motility. The signal pathways encompassed Pathways in cancer, Lipid and atherosclerosis, Fluid shear stress and atherosclerosis, as well as the AGE-RAGE. Bioinformatics analysis indicated TP53 was the core gene. Ultimately, the molecular docking revealed that wogonin, kaempferol, luteolin, and quercetin each exhibited significant affinity in their respective interactions with TP53. Notably, kaempferol exhibited the lowest binding energy, indicating a highly stable interaction with TP53. Lastly, we validated the stability of the binding interaction between the four small molecules and the TP53 through molecular dynamics simulations. The molecular dynamics simulation further validated the strongest binding between TP53 and kaempferol. In essence, our research groundbreaking in its nature elucidates for the first time the underlying molecular mechanism of CQD in the therapeutic management of schistosomiasis, thereby providing valuable insights and guidance for the treatment of this disease.ConclusionThis study uncovered the efficacious components and underlying molecular mechanisms of the Chufeng Qingpi Decoction in the management of schistosomiasis, thereby offering valuable insights for future fundamental research endeavors.","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142198006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complement C3 deposition restricts the proliferation of internalized Staphylococcus aureus by promoting autophagy","authors":"Yining Deng, Yunke Zhang, Tong Wu, Kang Niu, Xiaoyu Jiao, Wenge Ma, Chen Peng, Wenxue Wu","doi":"10.3389/fcimb.2024.1400068","DOIUrl":"https://doi.org/10.3389/fcimb.2024.1400068","url":null,"abstract":"Complement C3 (C3) is usually deposited spontaneously on the surfaces of invading bacteria prior to internalization, but the impact of C3 coating on cellular responses is largely unknown. <jats:italic>Staphylococcus aureus</jats:italic> (<jats:italic>S. aureus</jats:italic>) is a facultative intracellular pathogen that subverts autophagy and replicates in both phagocytic and nonphagocytic cells. In the present study, we deposited C3 components on the surface of <jats:italic>S. aureus</jats:italic> by complement opsonization before cell infection and confirmed that C3-coatings remained on the surface of the bacteria after they have invaded the cells, suggesting <jats:italic>S. aureus</jats:italic> cannot escape or degrade C3 labeling. We found that the C3 deposition on <jats:italic>S. aureus</jats:italic> notably enhanced cellular autophagic responses, and distinguished these responses as xenophagy, in contrast to LC3-associated phagocytosis (LAP). Furthermore, this upregulation was due to the recruitment of and direct interaction with autophagy-related 16-like 1 (ATG16L1), thereby resulting in autophagy-dependent resistance to bacterial growth within cells. Interestingly, this autophagic effect occurred only after C3 activation by enzymatic cleavage because full-length C3 without cleavage of the complement cascade reaction, although capable of binding to ATG16L1, failed to promote autophagy. These findings demonstrate the biological function of intracellular C3 upon bacterial infection in enhancing autophagy against internalized <jats:italic>S. aureus</jats:italic>.","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142198007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autophagy: the misty lands of Chlamydia trachomatis infection","authors":"Shan Zhang, Yufei Jiang, Yonghui Yu, Xuan Ouyang, Dongsheng Zhou, Yajun Song, Jun Jiao","doi":"10.3389/fcimb.2024.1442995","DOIUrl":"https://doi.org/10.3389/fcimb.2024.1442995","url":null,"abstract":"<jats:italic>Chlamydia</jats:italic> are Gram-negative, obligate intracellular bacterial pathogens that infect eukaryotic cells and reside within a host-derived vacuole known as the inclusion. To facilitate intracellular replication, these bacteria must engage in host-pathogen interactions to obtain nutrients and membranes required for the growth of the inclusion, thereby sustaining prolonged bacterial colonization. Autophagy is a highly conserved process that delivers cytoplasmic substrates to the lysosome for degradation. Pathogens have developed strategies to manipulate and/or exploit autophagy to promote their replication and persistence. This review delineates recent advances in elucidating the interplay between <jats:italic>Chlamydia trachomatis</jats:italic> infection and autophagy in recent years, emphasizing the intricate strategies employed by both the <jats:italic>Chlamydia</jats:italic> pathogens and host cells. Gaining a deeper understanding of these interactions could unveil novel strategies for the prevention and treatment of <jats:italic>Chlamydia</jats:italic> infection.","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142198012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomics of severe SARS-COV-2 infection and paraquat poisoning in human lung tissue samples: comparison of microbial infected and toxic pulmonary fibrosis","authors":"Jiang Min, Hou Jiaqi, Lin Lihua, Chai Qianqian, Wang Shujuan, Liu Xiang, Liu Liang, Ren Liang, Zhou Yiwu, Liu Qian","doi":"10.3389/fcimb.2024.1446305","DOIUrl":"https://doi.org/10.3389/fcimb.2024.1446305","url":null,"abstract":"IntroductionPulmonary fibrosis (PF) encompasses a spectrum of lung conditions characterized by the abnormal accumulation of scar tissue in the lungs, leading to impaired respiratory function. Various conditions can result in severe PF, among which viral infections have emerged as significant triggers. In addition to viral infections, exposure to toxic substances such as paraquat represents another significant risk factor for PF. Therefore, this study aimed to explore the dissimilarities and similarities between PF triggered by viral infections and chemical toxicants, using the mechanism of PF in IPF as a reference.MethodsData-independent acquisition proteomics technology was employed to identify COVID-19 and paraquat-induced PF from the autopsy of lung tissue samples obtained from individuals who died due to PF. Bioinformatics was employed for differential protein analysis, and selected indicators were validated on pathological sections.ResultsOur results showed that the differential proteins associated with the two causes of PF were enriched in similar lung fibrosis-related signaling pathways, such as the Wnt signaling pathway. However, differences were observed in proteins such as CACYBP, we verified the consistency of the results with proteomics using the IHC approachConclusionThis study illuminates distinct protein-level differences by investigating pulmonary fibrosis pathways in severe COVID-19 and paraquat poisoning. Although both conditions activate lung-protective and repair pathways, COVID-19 shows limited phosphorylation-independent ubiquitination of β-catenin compared to paraquat toxicity. These findings shed light on potential therapeutic targets for PF induced via diverse factors.","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142198010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intervention in gut microbiota increases intestinal γ-aminobutyric acid and alleviates anxiety behavior: a possible mechanism via the action on intestinal epithelial cells","authors":"Mion Ikegami, Hikari Narabayashi, Kazuaki Nakata, Miyu Yamashita, Yutaka Sugi, Yushiro Fuji, Hiroshi Matsufuji, Gaku Harata, Kazutoyo Yoda, Kenji Miyazawa, Yusuke Nakanishi, Kyoko Takahashi","doi":"10.3389/fcimb.2024.1421791","DOIUrl":"https://doi.org/10.3389/fcimb.2024.1421791","url":null,"abstract":"The role of the gut microbiota in the gut-brain axis has attracted attention in recent years. Some gut microbiota produces γ-aminobutyric acid (GABA), a major inhibitory neurotransmitter in mammals, <jats:italic>in vitro</jats:italic>, but the correlation between gut microbiota composition and intestinal GABA concentration, as well as the action of intestinal GABA <jats:italic>in vivo</jats:italic>, are poorly understood. Herein, we found that the intestinal GABA concentration was increased in mice by the intervention of the gut microbiota with neomycin or <jats:italic>Bifidobacterium bifidum</jats:italic> TMC3115 (TMC3115). Administration of TMC3115 reduced anxiety without affecting serum levels of serotonin, corticosterone, or GABA. We further found that intestinal epithelial cells expressed GABA receptor subunits and mediated mitogen-activated protein kinase signaling upon GABA stimulation. In addition, administration of TMC3115 induced mitogen-activated protein kinase signaling in colonic epithelial cells but not in small intestinal epithelial cells in mice. These results indicate that GABA produced by the gut microbiota, mainly in the colon, may affect host behavioral characteristics via GABA receptors expressed in intestinal epithelial cells without being transferred to the blood. This study suggests a novel mechanism by which intestinal GABA exerts physiological effects, even in the presence of the blood-brain barrier.","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142198009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting lon protease to inhibit persister cell formation in Salmonella Typhimurium: a drug repositioning approach","authors":"Negar Narimisa, Shabnam Razavi, Amin Khoshbayan, Sajjad Gharaghani, Faramarz Masjedian Jazi","doi":"10.3389/fcimb.2024.1427312","DOIUrl":"https://doi.org/10.3389/fcimb.2024.1427312","url":null,"abstract":"ObjectivePersister cells are a specific subset of bacteria capable of surviving exposure to lethal doses of antibiotics, leading to antibiotic therapy failures and infection relapses. This research explores the utilization of drug repositioning to target the Lon protease in <jats:italic>Salmonella</jats:italic> Typhimurium.MethodIn this study, FDA-approved drugs sourced from the Drug Bank database were screened to identify existing pharmaceuticals with the potential to combat the Lon protease. The formation of persister cells in the presence of antibiotics, as well as the combination of antibiotics with potential Lon protease inhibitors, was examined. Furthermore, the expression of type II toxin-antitoxin system genes was analyzed to enhance our comprehension of the inhibitors’ effects.ResultMolecular docking analysis revealed that Diosmin and Nafcillin exhibited strong binding affinity to the Lon protease. Molecular dynamics simulation trajectories analysis demonstrated that the interaction of these ligands with the enzyme did not induce instability; rather, the enzyme’s structure remained stable. Combinations of ceftazidime and ciprofloxacin with either Nafcillin or Diosmin led to significant reductions in bacterial cell counts. Furthermore, the effectiveness of these combinations, when compared to antibiotics alone, highlighted the substantial impact of Nafcillin and Diosmin in reducing type II TA system gene expression.ConclusionThese findings suggest promising prospects for developing novel therapeutic approaches targeting persister cells to mitigate treatment failures in <jats:italic>Salmonella</jats:italic> infections.","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142198011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}