Frontiers in Microbiology最新文献

{"title":"Human papillomavirus, vaginal microbiota and metagenomics: the interplay between development and progression of cervical cancer.","authors":"Paul Leon-Gomez, Vanessa I Romero","doi":"10.3389/fmicb.2024.1515258","DOIUrl":"10.3389/fmicb.2024.1515258","url":null,"abstract":"<p><p>Persistent infection with oncogenic human papillomavirus (HPV) types, such as HPV 16 or 18, is a major factor in cervical cancer development. However, only a small percentage of infected women develop cancer, indicating that other factors are involved. Emerging evidence links vaginal microbiota with HPV persistence and cancer progression. Alterations in microbial composition, function, and metabolic pathways may contribute to this process. Despite the potential of metagenomics to explore these interactions, studies on the vaginal microbiota's role in cervical cancer are limited. This review systematically examines the relationship between cervical microbiota, HPV, and cervical cancer by analyzing studies from PubMed, EBSCO, and Scopus. We highlight how microbial diversity influences HPV persistence and cancer progression, noting that healthy women typically have lower microbiota diversity and higher <i>Lactobacillus</i> abundance compared to HPV-infected women, who exhibit increased <i>Gardenella, Prevotella, Sneathia, Megasphaera, Streptococcus, and Fusobacterium</i> spp., associated with dysbiosis. We discuss how microbial diversity is associated with HPV persistence and cancer progression, noting that studies suggest healthy women typically have lower microbiota diversity and higher <i>Lactobacillus</i> abundance, while HPV-infected women exhibit increased <i>Gardnerella</i>, <i>Prevotella</i>, <i>Sneathia</i>, <i>Megasphaera</i>, <i>Streptococcus</i>, and <i>Fusobacterium</i> spp., indicative of dysbiosis. Potential markers such as <i>Gardnerella</i> and <i>Prevotella</i> have been identified as potential microbiome biomarkers associated with HPV infection and cervical cancer progression. The review also discusses microbiome-related gene expression changes in cervical cancer patients. However, further research is needed to validate these findings and explore additional microbiome alterations in cancer progression.</p>","PeriodicalId":12466,"journal":{"name":"Frontiers in Microbiology","volume":"15 ","pages":"1515258"},"PeriodicalIF":4.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual EMCV-IRES-integrated dengue virus can express an exogenous gene and cellular Mdm2 integration suppresses the dengue viral replication.","authors":"Tadahisa Teramoto","doi":"10.3389/fmicb.2025.1533062","DOIUrl":"10.3389/fmicb.2025.1533062","url":null,"abstract":"<p><p>Flaviviruses transmit through a wide range of vertebrate and arthropod hosts, while the other genera in <i>Flaviviridae</i> replicate in a limited set of vertebrate hosts. Flaviviruses possess a 5' cap in their genome RNA for translation, while the other genera utilize their internal ribosome entry site (IRES) sequences instead of a 5' cap. In this study, the translational modification to add an IRES sequence was examined. An IRES sequence derived from encephalomyocarditis (EMCV) was inserted into dengue virus serotype 2 (DENV2); a non-structural (NS) polyprotein was translated by IRES separately from 5' cap-induced structural polyprotein translation. It was revealed that the IRES-integrated DENV2 is prevented from replicating in C6/36 mosquito cells, suggesting that the 5' cap is an advantageous mechanism for flavivirus translation in invertebrate species. I further created dual IRES-integrated DENV2, in which a non-viral gene can be expressed by the flanking IRESs. The insertion of eGFP fluorescently visualized the virus spread. The renilla luciferase (Rluc) integration enabled the viral replication quantification. It was also revealed that a cellular gene, Mdm2, which antagonizes tumor suppressor protein p53 (TP53), could terminate the viral replication in BHK21 cells. Thus, the modifications of the DENV genome with IRES and the subsequent foreign gene could be utilized for controlling viral replications.</p>","PeriodicalId":12466,"journal":{"name":"Frontiers in Microbiology","volume":"16 ","pages":"1533062"},"PeriodicalIF":4.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The frequency of mutations in the <i>pen</i>A, <i>mtr</i>R, <i>gyr</i>A and <i>par</i>C genes of <i>Neisseria gonorrhoeae</i>, the presence of <i>tet</i>M gene and antibiotic resistance/susceptibility: a systematic review and meta-analyses.","authors":"Ana Clara Mendes, Renan Pedra de Souza, Diana Bahia","doi":"10.3389/fmicb.2024.1414330","DOIUrl":"10.3389/fmicb.2024.1414330","url":null,"abstract":"<p><p>Gonorrhoea is currently one of the most important sexually transmitted infections (STIs) due to the increasing spread of multidrug-resistant strains of <i>N. gonorrhoeae</i>. The aim of this study was to analyse the association between resistance or decreased susceptibility to antibiotics in <i>N. gonorrhoeae</i> and the presence of mutations in the <i>pen</i>A, <i>mtr</i>R, <i>gyr</i>A and <i>par</i>C genes, and the presence of tetM gene. We conducted a systematic review according to the PRISMA guidelines. We selected 19 studies for the <i>pen</i>A gene, 23 for <i>gyr</i>A and <i>par</i>C, 18 for <i>mtr</i>R and 12 for <i>tet</i>M using the Science Direct and PubMed databases. Meta-analyses of isolates resistant to penicillin, cefixime and ceftriaxone showed that more than 50% of isolates had mutations in the <i>pen</i>A and <i>mtr</i>R genes. More than 50% of azithromycin-resistant isolates had mutations in the <i>mtr</i>R gene, while more than 50% of ciprofloxacin-resistant and intermediate-resistant isolates had mutations in <i>gyr</i>A. Less than 50% of the isolates with intermediate resistance to ciprofloxacin had mutations in <i>par</i>C. The plasmid containing the <i>tet</i>M gene was found in more than 50% of tetracycline-resistant isolates. Infection surveillance and genetic studies are important for controlling the spread of the disease, which can improve the quality of life of infected people and reduce the financial burden on public health systems.</p>","PeriodicalId":12466,"journal":{"name":"Frontiers in Microbiology","volume":"15 ","pages":"1414330"},"PeriodicalIF":4.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11808683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of hepatitis B virus DNA levels with efficacy and safety and the impact of antiviral therapy on prognosis in liver cancer patients receiving immune checkpoint inhibitors therapy: a systematic review and meta-analysis.","authors":"Hongxia Cui, Su Li, Wu Lv, Jing Xiang","doi":"10.3389/fmicb.2025.1501139","DOIUrl":"10.3389/fmicb.2025.1501139","url":null,"abstract":"<p><strong>Background: </strong>The current evidence regarding the relationship between baseline hepatitis B virus (HBV) DNA levels and survival outcomes in liver cancer patients receiving immune checkpoint inhibitors (ICIs) remains inconsistent. Therefore, this review was intended to explore the impact of the baseline HBV-DNA level on the efficacy and safety of ICIs in patients with liver cancer.</p><p><strong>Methods: </strong>Relevant studies were identified through a comprehensive search in PubMed, EMBASE, Cochrane Library, and Web of Science up to August 1, 2024. The outcomes were hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), as well as odds ratios (ORs) for objective response rate (ORR), disease control rate (DCR) and HBV reactivation (HBVr). Subgroup analysis, publication bias, and sensitivity analysis were conducted with STATA 14.0.</p><p><strong>Results: </strong>This meta-analysis comprised 17 articles involving a total of 2,130 patients. The pooled results demonstrated that high HBV DNA was associated with a worse OS (HR = 1.48 95% CI 1.11-1.96). Further subgroup analysis showed that there was no difference in OS between the high HBV DNA group and low HBV DNA group when all patients received antiviral treatment. No associations between baseline HBV DNA and PFS (HR = 1.08, 95% CI 0.90-1.29), ORR (OR = 0.91, 95% CI 0.65-1.28), or DCR (OR = 0.83, 95% CI 0.58-1.20) were observed. The risk of HBVr in the high HBV DNA group was lower than that in the low HBV DNA group (OR = 0.30, 95% CI 0.15-0.58), especially among patients who received antiviral therapy (OR = 0.42, 95% CI 0.18-0.98).</p><p><strong>Conclusion: </strong>High HBV DNA was associated with worse OS, but not with PFS, ORR, or DCR in liver cancer patients receiving ICIs. When patients were simultaneously treated with antiviral treatment, elevated HBV DNA level had no unfavorable impact on the efficacy of ICIs. Furthermore, the risk of HBVr in the high HBV-DNA group was lower than that in the low HBV DNA group. More prospective studies with larger sample sizes are essential to confirm the results.</p>","PeriodicalId":12466,"journal":{"name":"Frontiers in Microbiology","volume":"16 ","pages":"1501139"},"PeriodicalIF":4.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep learning in microbiome analysis: a comprehensive review of neural network models.","authors":"Piotr Przymus, Krzysztof Rykaczewski, Adrián Martín-Segura, Jaak Truu, Enrique Carrillo De Santa Pau, Mikhail Kolev, Irina Naskinova, Aleksandra Gruca, Alexia Sampri, Marcus Frohme, Alina Nechyporenko","doi":"10.3389/fmicb.2024.1516667","DOIUrl":"10.3389/fmicb.2024.1516667","url":null,"abstract":"<p><p>Microbiome research, the study of microbial communities in diverse environments, has seen significant advances due to the integration of deep learning (DL) methods. These computational techniques have become essential for addressing the inherent complexity and high-dimensionality of microbiome data, which consist of different types of omics datasets. Deep learning algorithms have shown remarkable capabilities in pattern recognition, feature extraction, and predictive modeling, enabling researchers to uncover hidden relationships within microbial ecosystems. By automating the detection of functional genes, microbial interactions, and host-microbiome dynamics, DL methods offer unprecedented precision in understanding microbiome composition and its impact on health, disease, and the environment. However, despite their potential, deep learning approaches face significant challenges in microbiome research. Additionally, the biological variability in microbiome datasets requires tailored approaches to ensure robust and generalizable outcomes. As microbiome research continues to generate vast and complex datasets, addressing these challenges will be crucial for advancing microbiological insights and translating them into practical applications with DL. This review provides an overview of different deep learning models in microbiome research, discussing their strengths, practical uses, and implications for future studies. We examine how these models are being applied to solve key problems and highlight potential pathways to overcome current limitations, emphasizing the transformative impact DL could have on the field moving forward.</p>","PeriodicalId":12466,"journal":{"name":"Frontiers in Microbiology","volume":"15 ","pages":"1516667"},"PeriodicalIF":4.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BANNMDA: a computational model for predicting potential microbe-drug associations based on bilinear attention networks and nuclear norm minimization.","authors":"Mingmin Liang, Xianzhi Liu, Juncai Li, Qijia Chen, Bin Zeng, Zhong Wang, Jing Li, Lei Wang","doi":"10.3389/fmicb.2024.1497886","DOIUrl":"10.3389/fmicb.2024.1497886","url":null,"abstract":"<p><strong>Introduction: </strong>Predicting potential associations between microbes and drugs is crucial for advancing pharmaceutical research and development. In this manuscript, we introduced an innovative computational model named BANNMDA by integrating Bilinear Attention Networks(BAN) with the Nuclear Norm Minimization (NNM) to uncover hidden connections between microbes and drugs.</p><p><strong>Methods: </strong>In BANNMDA, we initially constructed a heterogeneous microbe-drug network by combining multiple drug and microbe similarity metrics with known microbe-drug relationships. Subsequently, we applied both BAN and NNM to compute predicted scores of potential microbe-drug associations. Finally, we implemented 5-fold cross-validation frameworks to evaluate the prediction performance of BANNMDA.</p><p><strong>Results and discussion: </strong>The experimental results indicated that BANNMDA outperformed state-of-the-art competitive methods. We conducted case studies on well-known drugs such as the Amoxicillin and Ceftazidime, as well as on pathogens such as <i>Bacillus cereus</i> and Influenza A virus, to further evaluate the efficacy of BANNMDA, and experimental outcomes showed that there were 9 out of the top 10 predicted drugs, along with 8 and 9 out of the top 10 predicted microbes having been corroborated by relevant literatures. These findings underscored the capability of BANNMDA to achieve commendable predictive accuracy.</p>","PeriodicalId":12466,"journal":{"name":"Frontiers in Microbiology","volume":"15 ","pages":"1497886"},"PeriodicalIF":4.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of microbial communities in flavors and fragrances during storage.","authors":"Yingjie Feng, Tingting Zhang, Jinchu Yang, Wenzhao Liu, Yongfeng Yang, Jihong Huang, Shen Huang, Zongcan Yang, Qianjin Liu, Wenchao Zheng, Qing Zhou","doi":"10.3389/fmicb.2025.1516594","DOIUrl":"10.3389/fmicb.2025.1516594","url":null,"abstract":"<p><p>Flavors and fragrances are essential for product quality, yet they are highly susceptible to contamination due to high moisture content and rich nutrients. This study investigates microbial growth, pH changes, volatile compound dynamics, and microbial community changes during the storage of flavors and fragrances. Results indicate that total viable counts (TVC) remained stable for the first three days but increased rapidly afterward, exceeding the acceptable limit of 5 log CFU/mL by day 7. The pH levels initially rose slightly, followed by a steady decline, which indicates spoilage progression. Gas chromatography-mass spectrometry (GC-MS) analysis revealed significant degradation of key aromatic compounds, such as 5-hydroxymethylfurfural (5-HMF), vanillin, and its derivative ethyl vanillin. Whole genome shotgun (WGS) sequencing demonstrated a marked increase in microbial community richness and diversity as storage progressed, with a notable shift in composition. Early storage stages were dominated by fungal species from the <i>Ascomycota</i> phylum, while later stages saw a rise in spoilage-associated bacteria, particularly from the <i>Firmicutes</i> and <i>Proteobacteria</i> phyla. Throughout the storage process, <i>Zygosaccharomyces</i> and its dominant species, <i>Zygosaccharomyces bailii</i>, remained prevalent, though their average relative abundance decreased from 81.26 to 32.29%. In addition, the bacterial species <i>Oceanobacillus sojae</i> and <i>Niallia nealsonii</i> showed significant increases in relative abundance, suggesting that bacteria were one of the key contributors to the spoilage of flavors and fragrances. Functional analysis based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database indicated a shift in metabolic pathways within the microbial community, with heightened metabolic activity correlating with spoilage. These findings provide valuable insights for improving storage methods and quality control of flavors and fragrances.</p>","PeriodicalId":12466,"journal":{"name":"Frontiers in Microbiology","volume":"16 ","pages":"1516594"},"PeriodicalIF":4.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Community structure and diversity of myxobacteria in soils from Inner Mongolia, China.","authors":"Zhihua Wu, Songyuan Li, Xuehan Wang, Huirong Liu","doi":"10.3389/fmicb.2024.1501573","DOIUrl":"10.3389/fmicb.2024.1501573","url":null,"abstract":"<p><p>Myxobacteria are a special kind of Gram-negative bacteria that can slide and produce a variety of bioactive substances against bacteria, fungi, and viruses. It has great development and research value in medicine and agriculture. Although myxobacteria have become a research hotspot at home and abroad, there are few systematic studies on the relationship between its diversity, geographical location, and environment factors. In order to solve these problems, 133 soil samples were collected from the east to the west of Inner Mongolia Autonomous Region and divided into five groups. The water content, pH, organic matter, available phosphorus, hydrolytic nitrogen, and available potassium content of soil samples were determined by national standards and other methods. The quantitative assessment of the abundance of myxobacteria in the soil sample was performed by quantitative real-time PCR. The composition of myxobacteria in the soil was determined by 16S rRNA high-throughput sequencing technology to analyze the differences in the community structure of myxobacteria among different groups, explore the relationship between the diversity of myxobacteria resources and the distribution and physical and chemical properties of the soil, and predict and analyze its community function. The results showed that there were abundant myxobacteria resources in the soils of Inner Mongolia, and the average relative abundance of myxobacteria in the soil samples from the central part of Inner Mongolia was higher than that in the eastern and western parts, but the richness and diversity of samples from the central to eastern regions were significantly higher than those from the western regions. The myxobacteria resources in the whole region included 10 families and 22 genera, among which the dominant genera were <i>Labilitrix</i>, <i>Sandaracinus</i>, <i>Archangium</i>, and <i>Haliangium</i>. The analysis of the species composition of myxobacteria among different groups found that the distribution of soil and soil type had an impact on the species composition of the samples. The species with significant differences in relative abundance among the five groups of samples were <i>Labilitrix</i>, <i>Archangium</i>, <i>Sandaracinus</i>, <i>Minicystis</i>, <i>Polyangium</i>, and <i>Myxococcus</i>. In addition, the latitude and longitude of the sampling point and the soil pH, water content, available phosphorus content and organic matter content had a greater impact on the myxobacteria community structure of samples, while the altitude of the soil sample and the contents of available potassium and alkaline nitrogen had a relatively small impact. Our data suggest that the distribution, type and nutrient composition of soil samples have an impact on the relative abundance and species composition of myxobacteria community. The completion of this work can provide basic data for the in-depth study of myxobacteria in the soil.</p>","PeriodicalId":12466,"journal":{"name":"Frontiers in Microbiology","volume":"15 ","pages":"1501573"},"PeriodicalIF":4.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness of antimicrobial agent combinations against carbapenem-producing <i>Klebsiella pneumoniae</i> with KPC variants in China.","authors":"Congcong Liu, Yuchen Wu, Yanyan Zhang, Zelin Yan, Danxia Gu, Hongwei Zhou, Ning Dong, Chang Cai, Gongxiang Chen, Rong Zhang","doi":"10.3389/fmicb.2024.1519319","DOIUrl":"10.3389/fmicb.2024.1519319","url":null,"abstract":"<p><strong>Purpose: </strong>Carbapenem-resistant <i>Klebsiella pneumoniae</i> (CRKP) producing carbapenemases poses a global threat to public health. Antimicrobial agent combinations have been promoted as a potential therapeutic strategy for infections. The most effective antimicrobial combinations against CRKP strains producing different carbapenemases are currently unclear, particularly those producing the KPC variant carbapenemases. This study is aimed to evaluate the effectiveness of various antimicrobial agent combinations against CRKP strains with different carbapenemases.</p><p><strong>Methods: </strong>A checkerboard assay involving 24 antimicrobial agent combinations was conducted on 44 strains of carbapenemase-producing CRKP isolated from patients of which 13 CRKP strains carried single KPC variants. The 24 antimicrobial combinations were based on meropenem, polymyxin, tigecycline, ceftazidime/avibactam, respectively. The fractional inhibitory concentration (FIC) indexes were calculated for each combination of antimicrobial agents.</p><p><strong>Results: </strong>The distribution of carbapenemases in 44 CRKP strains was as follows: KPC variants (<i>n</i> = 13, 29.5%), KPC-2 (<i>n</i> = 10, 22.7%), metallo-<i>β</i>-lactamases (<i>n</i> = 9, 20.5%), OXA-48-like (<i>n</i> = 12, 27.3%). In the checkerboard assay, the combination of polymyxin and aztreonam exhibited the highest synergistic effect against CRKP strains, with a rate of 95.5% (42/44). This was followed by polymyxin-meropenem at 88.6% (39/44) and polymyxin-levofloxacin at 68.2% (30/44). Additionally, polymyxin-aztreonam combination and polymyxin-meropenem showed the highest sum of synergistic and additive rates of 100.0% against KPC variant-producing CRKP strains. Notably, ceftazidime/avibactam-based combinations exhibited better synergistic effects on KPC variant-producing CRKP strains compared to other CRKP strains with adjusted <i>p</i> value <0.05.</p><p><strong>Conclusion: </strong>Our study suggests that the combinations of antimicrobial agent could serve as potential treatment strategies against CRKP infections. Furthermore, the effectiveness of these combinations is influenced by the types of carbapenemases present. Ceftazidime/avibactam-based combinations have showed superior synergistic effects on KPC variant-producing CRKP strains.</p>","PeriodicalId":12466,"journal":{"name":"Frontiers in Microbiology","volume":"15 ","pages":"1519319"},"PeriodicalIF":4.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesalazine: a novel therapeutic agent for periodontitis via regulation of periodontal microbiota and inhibiting <i>Porphyromonas gingivalis</i>.","authors":"Yuqi Wang, Jun Ma, Haoyu Wang, Jingzheng Yi, Yuxin Bai, Min Hu, Jiaqing Yan","doi":"10.3389/fmicb.2025.1531258","DOIUrl":"10.3389/fmicb.2025.1531258","url":null,"abstract":"<p><strong>Introduction: </strong>Periodontitis and inflammatory bowel disease are chronic inflammatory diseases with shared epidemiological, biological, and therapeutic associations. Given the similarities in their pathogenic factors, this study hypothesized that mesalazine, a key treatment agent for inflammatory bowel disease, could also be effective in managing periodontitis.</p><p><strong>Methods: </strong>The antimicrobial effect of mesalazine on <i>Porphyromonas gingivalis</i> was investigated <i>in vitro</i>, including observations of morphological changes on the surface of <i>P. gingivalis</i>. Additionally, the impact of mesalazine on both the formation and established plaque biofilms was examined. The antimicrobial mechanism was elucidated by assessing the expression of <i>P. gingivalis</i> virulence genes and by determining the disruptive effect on <i>P. gingivalis</i> cell membranes. An <i>in vivo</i> rat model of periodontitis was constructed to evaluate mesalazine's efficacy and its influence on the periodontal bacterial flora in the context of periodontitis.</p><p><strong>Results and discussion: </strong>Our results demonstrated that mesalazine concentrations ranging from 0.5 to 2 mg/mL significantly inhibited <i>P. gingivalis</i> proliferation over 72 h. Flow cytometry revealed a marked reduction in the number of viable cells following mesalazine treatment. At the nanometer scale, mesalazine induced crumpling and rupture of the <i>P. gingivalis</i> surface, compromising cell membrane integrity. Mesalazine not only suppressed the formation of plaque biofilms by <i>P. gingivalis</i> and polymicrobial communities but also disrupted pre-existing biofilms. The data also suggested that mesalazine could disrupt the integrity of the <i>P. gingivalis</i> cell membrane and inhibit the expression of virulence factors. An animal model of periodontitis in rats was successfully constructed <i>in vivo</i>. Mesalazine treatment inhibited alveolar bone resorption, alleviated inflammation of periodontal tissues, and improved the composition of the periodontal flora to a healthier state. This study establishes that mesalazine can treat periodontitis through modulation of the periodontal flora and its anti-inflammatory properties, thus broadening its classical therapeutic applications.</p>","PeriodicalId":12466,"journal":{"name":"Frontiers in Microbiology","volume":"16 ","pages":"1531258"},"PeriodicalIF":4.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}