Frontiers in Cellular and Infection Microbiology最新文献

{"title":"Combined multiplex polymerase chain reaction-based targeted next-generation sequencing and serum 1, 3-β-D-glucan for differential diagnosis of <i>Pneumocystis</i> pneumonia <i>and Pneumocystis</i> colonization.","authors":"Hansheng Wang, Xiao Chen, Xiaofeng Wu, Qizhen Cao, Yi Wu, Fang Wang, Yunyun Wang, Yanhui Zhou, Yijun Tang, Tao Ren, Meifang Wang","doi":"10.3389/fcimb.2025.1611391","DOIUrl":"https://doi.org/10.3389/fcimb.2025.1611391","url":null,"abstract":"<p><strong>Background and objective: </strong><i>Pneumocystis jirovecii</i> pneumonia (PjP) remains an important cause of morbimortality worldwide, and differentiating <i>Pneumocystis jirovecii</i> (<i>P. jirovecii</i>) infection from <i>P. jirovecii</i> colonization (PjC) is crucial for guiding treatment strategies. Multiplex polymerase chain reaction-based targeted next-generation sequencing (mp-tNGS) is a promising tool for identifying lower respiratory tract infections, with a detectable pathogen spectrum that covers more than 95% of clinical infectious cases. This study evaluated mp-tNGS for <i>P. jirovecii</i> identification in bronchoalveolar lavage fluid (BALF) samples combined with serum 1,3-β-D-glucan (BDG) level detection to differentiate PjP and PjC.</p><p><strong>Methods: </strong>A total of 73 patients were enrolled and the final diagnosis was used as a reference criterion, and patients were divided into the PjP group and PjC group. The clinical data and detection performance of mp-tNGS/serum BDG were analyzed.</p><p><strong>Results: </strong>The median fungal reads (normalized sequence counts) detected by mp-tNGS were 1522.00 (interquartile range [IQR], 581.5, 4898.0) in the PjP group versus 117.00 (IQR, 79.00, 257.00) in the PjC group (<i>p <</i>0.0001). Correspondingly, BDG levels were 122.5 (88.75,239.3) pg/ml in PjP patients compared to 59.00 (51.0,79.0) pg/ml in PjC patients (<i>p <</i>0.0001). Area under the receiver operator characteristic curve (AUROC) for discriminating PjP from colonization was 0.935 (95% CI: 0.88-0.99) for BALF mp-tNGS and 0.822 (95% CI: 0.72-0.93) for serum BDG. The optimal diagnostic thresholds were determined to be 355 reads for mp-tNGS (sensitivity: 89.1%; specificity: 85.2%) and 84.5 pg/ml for BDG (sensitivity: 85.2%; specificity: 80.4%).</p><p><strong>Conclusion: </strong>BALF mp-tNGS and serum BDG serve as valuable adjunct diagnostic tools, providing reliable differentiation between <i>P. jirovecii</i> colonization and active infection.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1611391"},"PeriodicalIF":4.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12489942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic and phenotypic characterization of antimicrobial resistance in clinical <i>Nocardia</i> species isolates.","authors":"Ziyu Song, Bingqian Du, Min Yuan, Jirao Shen, Shuai Xu, Wanchun Guan, Binghuai Lu, Zhenjun Li","doi":"10.3389/fcimb.2025.1672889","DOIUrl":"https://doi.org/10.3389/fcimb.2025.1672889","url":null,"abstract":"<p><strong>Background: </strong>Antimicrobial resistance is prevalent across <i>Nocardia</i> species, with varying resistance profiles among different species, which poses significant challenges to effective treatment strategies. Our study aimed to assess the antimicrobial susceptibility profiles of various <i>Nocardia</i> species and investigate the potential correlation between resistance phenotypes and their underlying genotypes.</p><p><strong>Methods: </strong>This study analyzed 148 clinical <i>Nocardia</i> isolates from 13 provinces in China. Minimum inhibitory concentrations (MICs) for 15 antimicrobial agents were determined using the microbroth dilution method. Whole genome sequencing (WGS) was performed for all isolates, followed by bioinformatics analyses integrated with 70 human-sourced <i>Nocardia</i> genomes in the National Center for Biotechnology Information (NCBI), encompassing species verification, phylogenetic analysis, and the identification of antimicrobial resistance genes (ARGs).</p><p><strong>Results: </strong>Average Nucleotide Identity (ANI) analysis reclassified several misidentified isolates and revealed 14 potentially novel <i>Nocardia</i> species, underscoring the taxonomic complexity within this genus. <i>Nocardia</i> species exhibited distinct resistance profiles: <i>Nocardia farcinica</i> demonstrated elevated resistance to cephalosporins and tobramycin; <i>Nocardia otitidiscaviarum</i> showed broad resistance to <i>β</i>-lactams and quinolones; and <i>Nocardia cyriacigeorgica</i> exhibited resistance to quinolones, cefepime, and cefoxitin. Notably, clarithromycin resistance was consistently high across all species. Moreover, 38.51% of <i>Nocardia</i> isolates are resistant to two or more commonly used antibiotics, which revealed widespread multidrug resistance (MDR). Strong genotype-phenotype correlations were observed, including <i>sul1</i> in sulfamethoxazole/trimethoprim-resistant <i>N. farcinica</i>, <i>bla</i> _AST-1 in <i>β</i>-lactam-resistant <i>N. otitidiscaviarum</i>, and <i>tetA/B(58)</i> across tetracycline-intermediate isolates. Additionally, resistance mechanisms beyond ARGs were observed, including species-specific presence of <i>warA</i> and <i>aph(2'')</i>, and <i>gyrA</i> mutations largely correlating with ciprofloxacin resistance. Nonetheless, resistance in some strains lacking known resistance determinants indicates the presence of uncharacterized mechanisms.</p><p><strong>Conclusions: </strong>These findings provide critical insights into the drug resistance patterns of <i>Nocardia</i> strains and antimicrobial resistance genes, highlighting the importance of ongoing genomic surveillance and personalized treatments.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1672889"},"PeriodicalIF":4.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12488653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Linking antibiotic resistance genes in the vaginal microbiota to health-related behaviors and antibiotic awareness in reproductive-age women: a cross-sectional study.","authors":"Paola Castellano, Camilla Ceccarani, Marielle Ezekielle Djusse, Michela Mazzetti, Sara Morselli, Tania Camboni, Silvia Conti, Federica Prinelli, Marco Severgnini, Claudio Foschi, Margherita Dall'Asta, Clarissa Consolandi, Antonella Marangoni","doi":"10.3389/fcimb.2025.1640992","DOIUrl":"https://doi.org/10.3389/fcimb.2025.1640992","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;The vaginal microbiota (VMB), predominantly shaped by &lt;i&gt;Lactobacillus&lt;/i&gt; species, plays a crucial role in maintaining vaginal health and preventing infections. However, its delicate balance is increasingly challenged by the widespread use of antibiotics and the consequent rise in antibiotic resistance genes (ARGs). While the VMB has been recognized as a potential reservoir for ARGs, limited research has explored how microbial composition, antibiotic exposure, and individual behavioral factors converge to shape the vaginal resistome.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Materials and methods: &lt;/strong&gt;In this cross-sectional study, vaginal swabs were collected from 105 reproductive-age Caucasian women. The VMB composition was characterized and classified into Community State Types (CSTs), by sequencing the hypervariable V3-V4 regions of the bacterial 16S rRNA gene. In order to highlight common patterns of abundance among taxa, a co-abundance groups (CAGs) analysis was performed. We assessed the distribution of 14 ARGs conferring resistance to macrolides, tetracyclines, beta-lactams, and quinolones along with two associated transposons by means of PCR. An overall composite ARGs score was also calculated. Participants completed detailed questionnaires assessing demographics and behavioral factors, with a particular focus on both health- and antibiotic-related behaviors. Statistical analyses examined associations between ARG prevalence, vaginal microbiome composition and relevant exposures.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;CSTs I and III were the most prevalent, with the most frequently detected ARGs being &lt;i&gt;erm(F)&lt;/i&gt;, &lt;i&gt;tet(M)&lt;/i&gt;, &lt;i&gt;erm(B)&lt;/i&gt;, &lt;i&gt;erm(A&lt;/i&gt;), and &lt;i&gt;tet(W)&lt;/i&gt;, each present in over 65% of participants. ARG presence was positively correlated with a higher vaginal microbiome alpha-diversity. Moreover, BV-associated bacterial taxa showed strong associations with ARGs, while &lt;i&gt;Lactobacillus&lt;/i&gt; species generally exhibited negative correlations. Smoking, a higher body mass index (BMI), presence of &lt;i&gt;Candida&lt;/i&gt; spp. and a history of antibiotic use were significantly associated with increased ARG prevalence, whereas oral contraceptive use and higher diet quality scores were negatively associated. Correlating together the relative abundances of the microbial CAGs and the presence/absence of specific ARGs, we found a positive association between several genes related to macrolide and tetracycline resistance and the &lt;i&gt;Gardnerella&lt;/i&gt;-&lt;i&gt;Prevotella&lt;/i&gt; CAG. Additionally, the &lt;i&gt;Gardnerella&lt;/i&gt;-&lt;i&gt;Prevotella&lt;/i&gt;, and the &lt;i&gt;Streptococcus&lt;/i&gt; CAGs were positively correlated to the total ARG score, whereas the &lt;i&gt;L. crispatus/jenesenii/gasseri&lt;/i&gt; CAG was negatively correlated.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;These findings underscore the role of the VMB as a dynamic reservoir of ARGs and highlight the influence of individual lifestyle and antibiotic-related behaviors on ARG dissemination in the vaginal niche. This suppor","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1640992"},"PeriodicalIF":4.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12488730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Performance of salivary microbiota in detecting periodontitis using a machine learning approach.","authors":"Shinya Kageyama, Shion Hama, Michiko Furuta, Mikari Asakawa, Shintaro Kawano, Toshiharu Ninomiya, Toru Takeshita","doi":"10.3389/fcimb.2025.1631798","DOIUrl":"https://doi.org/10.3389/fcimb.2025.1631798","url":null,"abstract":"<p><p>Altered salivary microbiota due to the progression of periodontitis may serve as a marker for simple and accurate identification of periodontitis. In this study, we examined saliva samples collected from 2,050 community-dwelling adults using 16S rRNA gene sequencing and verified the predictive performance of salivary microbiota in detecting periodontitis using a light gradient boosting machine algorithm. Five-fold stratified cross-validation was applied with 10 iterations, and the predictive performance was evaluated using the mean area under the receiver operating characteristic curve (AUC) value. In detecting periodontitis defined by number of teeth with probing depth ≥4 mm, localized (≥2 teeth), intermediate (≥4 teeth), and generalized (≥6 teeth) cases were detected with mean AUC values of 0.81 (95% confidence intervals, 0.80-0.81), 0.85 (0.84-0.86), and 0.87 (0.87-0.88), showing an increasing trend with extent. According to the Shapley additive explanation analysis, <i>Porphromonas gingivalis</i>, <i>Tannerella forsythia</i>, <i>Mycoplasma faucium, Treponema</i> species HMT-237, and <i>Fretibacterium</i> species HMT-362 were identified as important features for the detection of periodontitis. Our study presents the potential of salivary microbiota as a tool for mass screening of periodontitis and provides information on novel and important targets, including taxa other than known periodontal pathogens, to establish salivary screening tests.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1631798"},"PeriodicalIF":4.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12488677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single radiation exposure induces gut microbiota dysbiosis and decreases short-chain fatty acid metabolism and intestinal barrier integrity in mice.","authors":"Mineon Park, You Yeon Choi, Yanghee Lee, Minsu Cho","doi":"10.3389/fcimb.2025.1654976","DOIUrl":"10.3389/fcimb.2025.1654976","url":null,"abstract":"<p><p>Ionizing radiation causes biological damage, including DNA damage, inflammation, and tissue homeostasis disruption. The gastrointestinal tract, which harbors diverse gut microbiota, is particularly susceptible to radiation-induced injury and intestinal barrier dysfunction. We aimed to investigate the effects of single and fractionated radiation exposures on gut microbiota diversity and short-chain fatty acid (SCFA) metabolism. Mice were exposed to a single dose (1 Gy, one exposure; dose rate: 2.6 Gy/min) or fractionated doses (1 Gy accumulated over 75 fractions, 6.7 mGy/min for 2 min per session). <i>In vitro</i>, differentiated Caco-2 monolayers were used to assess radiation-induced tight junction disruption and reactive oxygen species (ROS) production. Single radiation exposure induced a stronger response than fractionated exposure, as evidenced by increased DNA damage foci, altered blood profiles, and elevated inflammatory cytokines. Gut dysbiosis was more pronounced in the single-radiation group, characterized by an increased Firmicutes/Bacteroidetes ratio and reduced microbial diversity. SCFA analysis revealed considerable reductions in acetic and propionic acid levels in the single-radiation group compared to those in the control and fractionated groups. The expression of the SCFA-sensing receptors GPR41 and GPR43 was markedly downregulated in the single-radiation group. Tight junction proteins (<i>TJP1, CLDN1, CLDN3</i>, and <i>OCLN</i>) were markedly decreased, indicating compromised intestinal barrier integrity and increased permeability both <i>in vivo</i> and <i>in vitro</i>. Single radiation exposure caused greater gut microbiota and metabolic disruptions than fractionated radiation exposure, emphasizing the distinct effects of each type and the critical roles of gut microbiota and SCFAs in radiation-induced intestinal damage.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1654976"},"PeriodicalIF":4.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12484129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From biofilm control to biomimetic remineralization: Hydrogels in prevention and treatment of dental caries.","authors":"Yuqing Chen, Shikang Lin, Xiaojing Huang, Wen Zhou","doi":"10.3389/fcimb.2025.1663563","DOIUrl":"10.3389/fcimb.2025.1663563","url":null,"abstract":"<p><p>Dental caries, a prevalent chronic bacterial disease globally, poses a significant threat to public health due to its complex pathogenesis involving demineralization and microbial dysbiosis. Hydrogels, with their unique three-dimensional network structures and diverse properties, have shown great potential in prevention and treatment of dental caries. This article systematically reviews recent advances in anti-caries hydrogel development. It first introduces the basis of anti-caries hydrogels, covering the applications of natural and semi-synthetic polymers as hydrogel matrices. Then, it elaborates on the mechanisms and research status of different types of anti-caries hydrogels, including probiotic formulations, antibacterial hydrogels, remineralization-inducing hydrogels, and saliva-related caries-reducing hydrogels. Finally, it summarizes the current research achievements and limitations and looks ahead to future research directions.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1663563"},"PeriodicalIF":4.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12484240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization and immunoprotection of thioredoxin reductase TrxB knockout mutant of <i>Salmonella</i> Enteritidis.","authors":"Siping Zhu, Lili Wang, Hong Li, Chihuan Li, Xintong Zhu, Chao Ren, Xiaochen Liu, Yulai Dong, Qiumei Shi, Zhiqiang Zhang","doi":"10.3389/fcimb.2025.1659729","DOIUrl":"10.3389/fcimb.2025.1659729","url":null,"abstract":"<p><strong>Background: </strong><i>Salmonella</i> Enteritidis (<i>S</i>. Enteritidis) is an important zoonotic pathogen that poses a major threat to animals and human health. TrxB, as a key component of the thioredoxin system, is a thioredoxin reductase ubiquitously present in organisms. It is mainly involved in maintaining cellular redox balance, but its role in the pathogenicity of <i>S</i>. Enteritidis remains unclear.</p><p><strong>Methods: </strong>In this study, we generated a <i>trxB</i>-deficient strain from <i>S</i>. Enteritidis C50336 strain to investigate how TrxB affects the biological characteristics and pathogenesis of the bacterium. The virulence of Δ<i>trxB</i> was assessed by measuring Δ<i>trxB</i> resistance to environmental stress, biofilm formation ability, motility, adhesion, invasion ability, intracellular survival, LD₅₀, virulence gene expression levels, and <i>in vivo</i> colonization ability. Additionally, the study measured specific IgG antibody levels in mice, lymphocyte proliferation, and the immunoprotective effect of Δ<i>trxB</i>.</p><p><strong>Results: </strong>We found that deletion of <i>trxB</i> gene did not affect the growth and biochemical properties of the <i>S</i>. Enteritidis strain but significantly reduced its motility, drug resistance, biofilm formation, and tolerance to environmental stress. After <i>trxB</i> knocked out, the adhesion and invasion capacities of <i>S</i>. Enteritidis to Caco-2 cells, along with its proliferation in RAW264.7 cells, were significantly reduced. Additionally, the <i>trxB</i>-deficient strain exhibited significantly lower pathogenicity than the parental strain, evidenced by a more than 100-fold increase in LD₅₀. We also observed a significant decrease in the expression of virulence-related genes in the <i>trxB</i>-knockout mutant. More importantly, immunization with this deletion strain can confer promising protection against challenge with the C50336 strain.</p><p><strong>Conclusion: </strong>These findings indicate that TrxB is a crucial virulence factor in <i>S</i>. Enteritidis, playing critical roles in its pathogenicity.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1659729"},"PeriodicalIF":4.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12484166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of antibiofilm compounds JG-1 and M4 across multiple species: alterations of protein interactions essential to biofilm formation.","authors":"Aliyah N Bennett, Jacob F Maziarz, Baileigh Laipply, Allysa L Cole, Katherine J Woolard, Amy Sorge, Michael J Zeiler, Roberta J Melander, Christian Melander, John S Gunn","doi":"10.3389/fcimb.2025.1631575","DOIUrl":"10.3389/fcimb.2025.1631575","url":null,"abstract":"<p><p>The majority of human bacterial pathogens have the ability to form biofilms <i>in vivo</i> on body tissues and implantable medical devices. Biofilm-mediated chronic bacterial infections are difficult to treat due to their recalcitrance to antimicrobials and immune effectors, often requiring invasive surgical intervention to clear the infection. The difficulty in effectively executing these treatment strategies underscores the need for therapeutic agents that specifically target the biofilm state. To this end, we previously identified two small molecules, JG-1 and M4, that <i>in vitro</i> effectively inhibit and disperse biofilms of <i>Salmonella</i> Typhimurium and members of the ESKAPE pathogen group, including <i>Enterobacter cloacae</i>, <i>Pseudomonas aeruginosa</i>, and <i>Acinetobacter baumannii</i>. In addition to its antibiofilm effects, M4 has a bactericidal effect on <i>Staphylococcus aureus</i> and <i>Enterococcus faecium</i>. While these compounds have promising utility as antimicrobial agents, their mechanism of action remains unknown. By employing multiple techniques including RNAseq, thermal proteome profiling, and site directed mutagenesis, we identified multiple proteins essential to biofilm formation and evaluated their role in the presence of JG-1 and M4 in mutant and wildtype backgrounds. We report that the JG-1 and M4 actions are influenced by proteins important to biofilm maintenance, including OmpA, OmpC, and TrxA. Compound-bacteria interactions cause transcriptional changes that result in biofilm dispersal, and modulation of other virulence mechanisms, including invasion and motility. Additionally, we report that M4 interacts with <i>S. aureus</i> CodY, which promotes cell death, while the specific targets in <i>S</i>. Typhimurium and <i>E. cloacae</i> remain elusive. Collectively, this study presents an empirical investigation into JG-1 and M4's mechanism of action in <i>S</i>. Typhimurium, <i>E. cloacae</i>, and <i>S. aureus</i>, and how the antibiofilm compounds disrupt microbial community dynamics, ultimately driving biofilm dispersal or cell death.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1631575"},"PeriodicalIF":4.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12484186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nicorandil reduces the antimicrobial effectiveness of polymyxin E against <i>Klebsiella pneumoniae</i> by decreasing reactive oxygen species accumulation.","authors":"Rongqing Zhu, Fangxin Luo, Chenxi Yuan, Ziqian Fang, Yaqin Guo, Bao Meng, Dongmei Zhao, Yanyan Liu, Yi Yang, Yasheng Li, Jiabin Li, Liang Yu","doi":"10.3389/fcimb.2025.1658194","DOIUrl":"10.3389/fcimb.2025.1658194","url":null,"abstract":"<p><p>Nitric oxide (NO) plays a crucial role in bacterial physiology and survival, particularly in relation to antibiotic resistance. The protective role of NO against antibiotics is intricate, and the potential antagonistic interactions between NO donors and polymyxin E remain largely unexplored. This study aimed to evaluate the antagonistic effects of nicorandil, a NO donor, on the bactericidal activity of polymyxin E against <i>Klebsiella pneumoniae</i>.</p><p><strong>Methods: </strong>Thirty clinical strains were identified as multidrug-resistant <i>K. pneumoniae</i> using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The antimicrobial efficacy of polymyxin E combined with nicorandil against <i>K. pneumoniae</i> was evaluated through <i>in vitro</i> rapid killing assays and growth curve analyses, and <i>in vivo</i> using a murine pulmonary infection model and a <i>Galleria mellonella</i> larvae infection model. The release of NO by nicorandil was confirmed via reactive nitrogen species (RNS) assays. The impact of NO on oxidative stress responses induced by polymyxin E was evaluated using reactive oxygen species (ROS) assays and RT-qPCR.</p><p><strong>Results: </strong>Nicorandil counteracted the bactericidal effects of polymyxin E in 16 out of 30 clinical isolates of <i>K. pneumoniae</i>. Notably, the most pronounced effects were observed in the <i>K. pneumoniae</i> strain GN 191035. In this context, the release of NO from nicorandil conferred protection to the bacteria against oxidative stress by reducing ROS, as demonstrated by a murine model of pulmonary infection and a <i>Galleria mellonella</i> larvae infection model.</p><p><strong>Conclusions: </strong>Our study further elucidated that nicorandil treatment mitigates the bactericidal efficacy of polymyxin E against <i>K. pneumoniae</i>. These findings highlight the significant risk of increased bacterial infections associated with the concurrent administration of nicorandil and polymyxin E.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1658194"},"PeriodicalIF":4.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12484039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid identification of major <i>Mycobacterium</i> species by loop-mediated isothermal amplification assay using novel species-specific genomic targets.","authors":"Yuanwu Zou, Zhuo Wang, Zihan Wei, Guanghong Bai, Xiaolin Wang, Shaoyi Qu, Guowei Zhong, Yanbin Gao","doi":"10.3389/fcimb.2025.1653602","DOIUrl":"10.3389/fcimb.2025.1653602","url":null,"abstract":"<p><strong>Background: </strong>Rapid and precise identification of <i>Mycobacterium</i> species is critical for appropriate clinical management and epidemiological surveillance. However, conventional methods often fail to differentiate closely related nontuberculous mycobacteria (NTM) species, limiting their clinical utility.</p><p><strong>Methods: </strong>We developed a multiplex loop-mediated isothermal amplification (LAMP) assay targeting newly identified species-specific genomic markers for simultaneous detection of <i>Mycobacterium tuberculosis</i> complex (MTBC) and six clinically important NTM species. Analytical performance was assessed using serial dilutions of bacterial cultures and 36 reference strains. Clinical validation was performed on 52 cultured isolates and 349 sputum samples, compared to GeneXpert MTB/RIF and a commercial PCR-reverse dot blot assay.</p><p><strong>Results: </strong>The assay showed high analytical sensitivity, with limits of detection ranging from 76.013 CFU/mL (95% CI: 60.329-113.924 CFU/mL) for MTBC to 166.602-690.629 CFU/mL for NTM species. All reference strains were correctly identified with no cross-reactivity. Among the clinical isolates, all targeted species were accurately detected. One isolate misidentified as <i>M. abscessus</i> by an ITS-based assay was confirmed by sequencing to be <i>M. massiliense</i>, demonstrating the assay's superior discriminatory capacity. For sputum samples, the assay achieved 90.32% sensitivity and 97.55% specificity for MTBC, with an overall agreement of 93.70% (κ = 0.8740).</p><p><strong>Conclusion: </strong>This multiplex LAMP assay offers a rapid, accurate, and field-deployable tool for species-level identification of MTBC and major NTM pathogens. Its simplicity, stability, and compatibility with low-resource settings support its application in routine diagnostics and decentralized tuberculosis programs.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1653602"},"PeriodicalIF":4.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12484021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}