Microbiology spectrum最新文献

{"title":"Antimicrobial peptide CEC-TY1: a potential antibacterial drug against carbapenem-resistant <i>Klebsiella pneumoniae</i>.","authors":"Yaozhu Yang, Hailong Yang, Qiuyue He, Min Niu, Kai Yang, Yongshi Zhao, Shumin Liu, Yan Du","doi":"10.1128/spectrum.00543-25","DOIUrl":"https://doi.org/10.1128/spectrum.00543-25","url":null,"abstract":"<p><p>Carbapenem-resistant <i>Klebsiella pneumoniae</i> (CRKP) infections in hospitals and the issues arising from their rapid spread have become significant public health challenges. Therefore, a new class of effective and safe antibacterial drugs is urgently required. In this study, we identified an antimicrobial peptide in the cecropin family, cecropin-TY1 (CEC-TY1), from the salivary glands of the horsefly. CEC-TY1 showed significant antibacterial activity against gram-negative bacteria, at concentrations up to 100 μg/mL, with no observed cytotoxicity or hemolytic activity against cells. Moreover, CEC-TY1 protected mice from lethal infections of CRKP <i>in vivo</i>, improving the survival rate of the infected mice. This peptide also alleviated excessive and harmful inflammatory responses by inhibiting the production of interleukin (IL)-6, tumor necrosis factor-α, and IL-1β.IMPORTANCEAntimicrobial peptides are a promising alternative to antibiotics in the current antibiotic resistance crisis. Specifically, the antimicrobial peptide cecropin-TY1 (CEC-TY1), identified in the salivary glands of horseflies, showed significant antibacterial activity against carbapenem-resistant <i>Klebsiella pneumoniae</i> (CRKP), both <i>in vitro</i> and <i>in vivo</i>. CEC-TY1 also has selective toxicity and low hemolytic activity and is therefore a potential therapeutic agent for acute CRKP infection.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0054325"},"PeriodicalIF":3.8,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145301927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Montelukast treats <i>Streptococcus pneumoniae</i>-induced sepsis via antibacterial and anti-inflammatory activities.","authors":"Wei Cao, Dongjun Xu, Huijie Yu, Xuning Shen","doi":"10.1128/spectrum.01221-25","DOIUrl":"https://doi.org/10.1128/spectrum.01221-25","url":null,"abstract":"<p><p><i>Streptococcus pneumoniae</i> is a leading causative pathogen of community-acquired pneumonia and sepsis. The increasing prevalence of antibiotic resistance among <i>S. pneumoniae</i> strains poses a major challenge to conventional antibiotic therapies. This study aimed to systematically evaluate the antibacterial, anti-biofilm, and <i>in vivo</i> therapeutic effects of montelukast against <i>S. pneumoniae</i> and to explore its potential for drug repurposing as an anti-infective agent. <i>In vitro</i> susceptibility testing revealed that montelukast exhibited inhibitory activity against both standard reference strains and 11 clinical multidrug-resistant (MDR) <i>S. pneumoniae</i> isolates, with minimum inhibitory concentrations (MICs) ranging from 4 to 32 µg/mL. Time-kill assays using the representative MDR strain S12 showed that montelukast at 16 µg/mL could completely eradicate bacteria within 8 h. And biofilm assays further demonstrated that montelukast at concentrations of 8-16 µg/mL significantly disrupted preformed biofilms and reduced viable bacterial counts within mature biofilms, suggesting its potential to combat chronic infections. In a mouse model of sepsis, montelukast treatment significantly improved survival rates of infected mice, with the 10 mg/kg dosage group achieving a 7-day survival rate of 80%. Quantification of bacterial burden revealed a marked reduction in colony-forming units (CFUs) in both blood and lung of montelukast-treated mice. Furthermore, analysis of serum inflammatory cytokines indicated that montelukast effectively suppressed the secretion of pro-inflammatory mediators such as TNF-α and IL-6, suggesting a dual role in infection control and inflammation modulation. In conclusion, montelukast exhibits potent anti-<i>S</i>. <i>pneumoniae</i> activity, including bactericidal effects against resistant strains, biofilm disruption capabilities, and synergistic antibacterial and anti-inflammatory effects <i>in vivo</i>. These findings support the potential repurposing of montelukast as a therapeutic agent for <i>S. pneumoniae</i> infections, particularly sepsis.</p><p><strong>Importance: </strong>Montelukast showed promise as a repurposed treatment for multidrug-resistant <i>Streptococcus pneumoniae</i>, especially in severe infections like sepsis. It demonstrated strong <i>in vitro</i> activity against both sensitive and resistant strains and exerted concentration-dependent bactericidal effects and cleared biofilms. In a mouse sepsis model, montelukast improved survival, reduced bacterial load, and mitigated inflammation. Mechanistically, it disrupted membrane integrity and induced oxidative stress and may target pseudouridine synthase. These findings supported montelukast's potential as an antimicrobial with dual antibacterial and anti-inflammatory action.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0122125"},"PeriodicalIF":3.8,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidemiology of respiratory syncytial virus in young, hospitalized children in Jordan: a prospective viral surveillance study.","authors":"Justin Z Amarin, Haya Hayek, Olla Hamdan, Yasmeen Z Qwaider, Tala Khraise, Ahmad Khader, Qusai Odeh, Rami Salim, Hadeel Shalabi, Ahmad Alhajajra, Yousef Khader, Basim Al-Zoubi, Najwa Khuri-Bulos, Andrew J Spieker, Leigh M Howard, James D Chappell, Natasha B Halasa","doi":"10.1128/spectrum.01727-25","DOIUrl":"https://doi.org/10.1128/spectrum.01727-25","url":null,"abstract":"<p><p>Respiratory syncytial virus (RSV) is a leading cause of hospitalization in young children. Understanding RSV burden and seasonality is crucial for implementing effective preventive strategies, especially in the wake of disruptions related to the coronavirus disease 2019 (COVID-19) pandemic. We aimed to determine RSV burden and seasonality among young children hospitalized in Jordan. We conducted a prospective viral surveillance study at Al-Bashir Hospital (1 November 2023 to 4 April 2024). Children <5 years old hospitalized with fever or respiratory symptoms were eligible. Nasal (and optional throat) swabs were collected and tested for common respiratory viruses using real-time polymerase chain reaction. We compared characteristics and outcomes of hospitalizations by RSV detection status and assessed RSV seasonality. Of 2,610 children, RSV was detected in 713 (27.3%), making it the second most common virus overall and the most common in children <2 years old (<i>n</i> = 680 [30.0%]). Children with RSV were more likely than those without RSV to receive low-flow oxygen (74.9% vs 23.2%; <i>P</i> < 0.001) and high-flow nasal cannulation (3.2% vs 1.2%; <i>P</i> < 0.001) and were more likely to be admitted to the intensive care unit (13.2% vs 8.2%; <i>P</i> < 0.001). At least one other respiratory virus was co-detected with RSV in 244 children (34.2%). During the 2023-2024 season, RSV circulation exhibited a clear winter seasonality, consistent with historical patterns. In conclusion, the burden of RSV in children in Jordan remains substantial following the COVID-19 pandemic. The return to historical winter seasonality has important implications for the timing of preventive interventions. Continued surveillance is crucial for monitoring RSV epidemiology in this region.</p><p><strong>Importance: </strong>This study confirms the persistent and significant burden of respiratory syncytial virus (RSV) among young, hospitalized children in Jordan. Crucially, our data reveal the normalization of RSV circulation patterns in 2024 following disruptions related to the coronavirus disease 2019 pandemic. This finding has important implications for optimizing the timing of preventive interventions, such as monoclonal antibodies and maternal vaccination, particularly in a resource-limited setting where they are costly and limited in availability. By providing these contemporary surveillance data from the Eastern Mediterranean-where sentinel surveillance platforms are lacking-this work has the potential to inform public health strategies directly and emphasizes the critical need for sustained monitoring to guide effective RSV prevention and control efforts.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0172725"},"PeriodicalIF":3.8,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response of <i>Escherichia coli</i> chemotaxis pathway to pyrimidine deoxyribonucleosides.","authors":"Malay Shah, Wenhao Xu, Victor Sourjik","doi":"10.1128/spectrum.02048-25","DOIUrl":"https://doi.org/10.1128/spectrum.02048-25","url":null,"abstract":"<p><p>Nucleosides are essential components of all living cells. Bacteria use salvage pathways to import nucleosides from their environment and to utilize them for nucleic acid biosynthesis, but also as alternative sources of carbon, nitrogen and energy. Motile bacteria commonly show chemoattraction towards nutritionally valuable compounds, and in this work, we demonstrate that the chemotaxis pathway of <i>Escherichia coli</i> exhibits specific attractant response to pyrimidine nucleosides. The most sensitive response, in the sub-micromolar range, was observed for pyrimidine deoxyribonucleosides, thymidine (deoxythymidine) and deoxycytidine. In contrast, pyrimidine ribonucleosides elicited weaker and less sensitive response, and no response to pyrimidine nucleobases was observed in the micromolar range of concentrations. Furthermore, no response was observed to tested purine nucleosides or nucleobases. Our subsequent analysis revealed that the pathway response to pyrimidine deoxyribonucleosides is mediated by the minor <i>E. coli</i> chemoreceptor Tap, whereas the response to the ribonucleoside uridine relies on a different mechanism. The observed narrow dynamic range of this response indicates that sensing of deoxyribonucleosides is indirect, likely via an unknown periplasmic binding protein that interacts with Tap.IMPORTANCEChemotactic behavior is highly important for bacterial ecology, enabling motile bacteria to locate environments that are optimal for growth, and it became a paradigm for bacterial environmental sensing and signal transduction. However, even for model organisms, the spectrum of stimuli sensed by the chemotaxis pathway is not fully known, which limits our understanding of the physiological and ecological relevance of the chemotactic behavior. Here, we identified pyrimidine deoxyribonucleosides as a novel and highly specific class of chemoeffector metabolites for <i>Escherichia coli</i>, the most studied chemotaxis model. Our work expands the number of bacterial species that exhibit chemotactic responses to nucleotide derivatives, strengthening the notion that pyrimidines and purines constitute a highly important class of chemoeffectors for many bacteria.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0204825"},"PeriodicalIF":3.8,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145286519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Variability in gastrointestinal multiplex PCR panel ordering in urgent care: a potential diagnostic stewardship target.","authors":"Timothy C Jenkins, Melody A Zwakenberg, Margaret Cooper, Katherine C Shihadeh, Michael Breyer, Cory K Hussain, Laura Triplett, Lindsey E Fish","doi":"10.1128/spectrum.02382-25","DOIUrl":"https://doi.org/10.1128/spectrum.02382-25","url":null,"abstract":"","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0238225"},"PeriodicalIF":3.8,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145286576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation dynamics and assembly of root zone soil bacterial communities in response to stress-associated phytohormones.","authors":"Sreejata Bandopadhyay, Oishi Bagchi, Ashley Shade","doi":"10.1128/spectrum.01789-25","DOIUrl":"https://doi.org/10.1128/spectrum.01789-25","url":null,"abstract":"<p><p>Plants can \"cry for help\" to recruit supportive microbiome members during stress, but the precise signals a plant uses to activate and assemble these microorganisms remain unclear. We evaluated the activation dynamics of root zone soil bacteria in response to phytohormones produced when plants are stressed, hypothesizing that responsive taxa could support plant resilience. We conducted a mesocosm experiment using root zone soil collected from the planted fields of two crops: the annual legume common bean (<i>Phaseolus vulgaris</i> L.) and the perennial grass switchgrass (<i>Panicum virgatum</i>). In the absence of any plant, we inactivated the root zone microbiome by drying the soil and then added abscisic acid, salicylic acid, a carrier control, or water to test their capacities to reactivate microbiome members and assessed responses for 2 weeks. Using amplicon sequencing of the 16S rRNA and rRNA genes to determine active populations, we found several actinobacteria that became active after exposure to abscisic acid and salicylic acid, with <i>Microbispora</i> lineages being especially responsive. While some taxa activated only in one crop's root soil, others were activated in both crops' soils in response to the same phytohormone. By comparing microbes that immediately activated 24 h after phytohormone addition with those that activated and also persisted over several days, we distinguished taxa that responded to phytohormones as signals from those that potentially also used them as resources. This work suggests that different root zone bacteria exhibit distinct specificities to phytohormones, providing insights into the signals by which plants may \"cry for help\" to recruit bacteria.</p><p><strong>Importance: </strong>Global food security is a pressing societal challenge that has been exacerbated by climate change and other anthropogenic stressors on the environment. Microbial bioinoculants are a promising solution for improving crop health and resilience, but ensuring their persistence and activation in the field remains a significant challenge. This study examined how dormant root-zone-associated bacteria reactivate after exposure to the plant stress hormones abscisic acid and salicylic acid. The experiment revealed that certain bacterial taxa could reactivate in response to these plant stress signals and persist for at least 2 weeks. This work advances our understanding of the potential cues for reactivating beneficial plant-associated microbes and supports the goal of developing microbial solutions for sustainable agriculture.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0178925"},"PeriodicalIF":3.8,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145286571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A specific, stable, and accessible LAMP assay targeting the HSP70 gene of <i>Trypanosoma cruzi</i>.","authors":"Sneider Alexander Gutierrez Guarnizo, Beth Jessy Condori, Luciana Basma, Shirley Equilia, Edith Malaga, Siena Defazio, Emily Arteaga, Jean Karla Velarde, Martín Obregón, Anshule Takyar, Carolina Duque, Jill Hakim, Freddy Tinajeros, Robert H Gilman, Natalie Bowman, Monica R Mugnier","doi":"10.1128/spectrum.00172-25","DOIUrl":"10.1128/spectrum.00172-25","url":null,"abstract":"<p><p>Diagnostic delays prevent most Chagas disease patients from receiving timely therapy during the acute phase when treatment is effective. Quantitative PCR (qPCR)-based diagnostic methods provide high sensitivity during this phase but require specialized equipment and complex protocols. More simple and cost-effective tools are urgently needed to expand early Chagas disease diagnosis in low-income endemic regions. Here, we present a loop-mediated isothermal amplification (LAMP) that targets a highly conserved region in the HSP70 gene of <i>Trypanosoma cruzi</i>, the causative agent of Chagas disease. This assay demonstrates species-specific amplification across multiple parasite genetic lineages while maintaining stability after 1 hour of incubation and at least 8 months of storage at -20°C. Moreover, the assay is at least 12 times less expensive than the TaqMan qPCR that is currently routinely used for acute Chagas diagnostics and is compatible with a low-cost CTAB-based DNA extraction method. Population-based validation in 100 infants born to Chagas-positive mothers in Santa Cruz, Bolivia, yielded a specificity of 100% and sensitivity exceeding 77% when compared to a TaqMan qPCR that targets satellite DNA. This cost-effective DNA extraction method and LAMP assay demonstrate potential for diagnosing Chagas disease in resource-limited endemic regions, particularly where qPCR is unavailable.</p><p><strong>Importance: </strong>Chagas disease, caused by the parasite <i>Trypanosoma cruzi</i>, is a life-threatening illness that disproportionately affects resource-limited communities. Congenital Chagas disease, if diagnosed early, presents a unique opportunity for intervention, as treatment in newborns is highly effective with minimal side effects. However, early diagnosis is hindered by the high cost and limited availability of current molecular diagnostic methods in endemic regions. Our study introduces a simple, low-cost, and highly specific LAMP assay targeting the HSP70 gene of <i>T. cruzi</i>. This assay is user-friendly, stable under varying storage and incubation conditions, and designed for accessibility in underserved areas. By providing a detailed, open-access protocol and primers, we aim to facilitate the widespread adoption of this diagnostic assay, enabling earlier detection and treatment. This assay lays the groundwork for a new approach to Chagas disease management, potentially reducing the spread of Chagas disease and improving public health outcomes in vulnerable populations globally.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0017225"},"PeriodicalIF":3.8,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145286529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carglumic acid and mesalazine as potential anti-mycobacterial agents: a spectroscopic study for repurposing drugs against <i>Mycobacterium tuberculosis</i> targeting its essential enzyme ThyX.","authors":"Sana Tanweer, Meetu Agarwal, Kunal Malik, Rahul Sharma, Shivani A Muthu, Md Abrar Siddiquee, Khushbu Sharma, Isha Pahuja, Waseem Ali, Abhinav Grover, Ved Prakash Dwivedi, Basir Ahmad, Sonam Grover","doi":"10.1128/spectrum.02486-24","DOIUrl":"https://doi.org/10.1128/spectrum.02486-24","url":null,"abstract":"<p><p><i>Mycobacterium tuberculosis (M.tb</i>) needs a key enzyme called ThyX to make thymidylate, which is essential for DNA replication and cell survival. In our previous study, carglumic acid (CGA) and mesalazine (MSZ) emerged as promising candidates from a Food and Drug Administration-approved drug library, selected through <i>in silico</i> screening. Our current investigation delves into the impact of CGA and MSZ on ThyX's biophysical properties. Utilizing fluorescence quenching, thermal, chemical denaturation, characterization, and circular dichroism spectroscopy, we probed the interaction between ThyX and the drugs. Our results confirm that both CGA and MSZ effectively quench ThyX's intrinsic fluorescence via a static quenching mechanism, leading to structural alterations in the protein. In subsequent <i>in vitro</i> and <i>ex vivo</i> studies, we determined that MSZ and CGA exhibit minimum inhibitory concentrations of 6.25 and 3.12 µg/mL, respectively, against <i>M.tb</i>. Notably, the survival of <i>M.tb</i> within RAW macrophages significantly decreased upon treatment with CGA and MSZ compared to untreated controls. In summary, our findings support the potential repurposing of CGA and MSZ as anti-tuberculosis (TB) drugs. Further validation in animal and clinical models is essential to assess their suitability for TB treatment.IMPORTANCEThyX (<i>Rv2754c</i>), flavin-dependent thymidylate synthase, is a crucial enzyme required by <i>Mycobacterium tuberculosis</i> for DNA replication and RNA maturation, making it a potential drug target to explore novel anti-tuberculosis (TB) treatments. Given the essentiality of ThyX, it was screened against Food and Drug Administration-approved drugs using molecular docking screening, and carglumic acid (CGA) and mesalazine (MSZ) were selected as potential inhibitors. To validate and explore their anti-mycobacterial potential, molecular dynamic simulation of these drugs in the presence of ThyX was carried out, and these studies were validated using <i>in vitro</i> biophysical characterization to establish their binding kinetics and effects of these drugs on the stability and structural changes of ThyX. Lastly, <i>in vitro</i> and <i>ex vivo</i> anti-mycobacterial activity of CGA and MSZ establish them as probable candidates for management of TB.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0248624"},"PeriodicalIF":3.8,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The influence of TC0668 on glycometabolism modulation in <i>Chlamydia muridarum</i>-infected host cells.","authors":"Nanyan Yu, Xuan Chen, Wenjing Yang, Yang Zhou, Yuchen Hu, Zhou Zhou","doi":"10.1128/spectrum.03051-24","DOIUrl":"https://doi.org/10.1128/spectrum.03051-24","url":null,"abstract":"<p><p><i>Chlamydia,</i> an obligate intracellular parasite, depends entirely on host cells for energy and biosynthesis while exerting pathogenic effects through its virulence factors. <i>Chlamydia muridarum</i> (<i>Cm</i>), an alternative model strain to <i>Chlamydia trachomatis</i> (<i>Ct</i>), modulates cellular metabolism to enhance its survival and pathogenicity during infection. We found that TC0668, a crucial <i>Cm</i> virulence protein associated with fallopian tube lesions in infected mice, induces a hypermetabolic state in host cells upon <i>Cm</i> stimulation. This results in alterations in glucose consumption, mitochondrial TCA cycle activity, aerobic glycolysis, and intracellular ATP levels. Specifically, infection with the <i>Cm</i> TC0668^wt strain in HeLa and HUVEC cells led to the activation of PI3K (p110) and substantial phosphorylation of AKT at S473. This activation was significantly reduced by LY-294002, a potent PI3K/AKT pathway inhibitor, which led to decreased glucose consumption and ATP levels in HUVECs. However, in HeLa cells, inhibition of the pathway primarily affected GLUT1 expression and ATP levels without impacting glucose consumption. These findings underscore the pivotal role of PI3K/AKT signaling in regulating cellular glycometabolism under the influence of the TC0668 protein during <i>Cm</i> infection.IMPORTANCEPrevious studies have identified that TC0668, as a virulence factor involved in the formation of fallopian tube hydrosalpinx caused by <i>Chlamydia muridarum</i> (<i>Cm</i>), is primarily involved in metabolic processes, cellular processes, and biological regulation, and there are notable differences in PI3K activation and AKT phosphorylation induced by <i>Cm tc0668</i> single-gene strains. However, the relationship between TC0668's influence on <i>Cm</i>-regulated glycometabolism and the activation of the PI3K/AKT pathway remains unclear. Our study established a vitro cell infection model of <i>Cm</i> using HeLa cells and HUVEC cells, and employed techniques such as Western blotting to reveal a novel mechanism of TC0668 in enhancing the pathogenicity of <i>Cm</i> by regulating host glycometabolism. The study advances our understanding of intracellular pathogen-host interactions and provides novel therapeutic strategies for <i>Chlamydia</i> infections.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0305124"},"PeriodicalIF":3.8,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the ocular microecology and its role in pterygium based on metagenomics.","authors":"Qiheng Yuan, Yiying Yang, Yangyang Shen, Bianjin Sun, Siwen Chen, Chengzhi Zheng, Yongliang Lou, Meiqin Zheng","doi":"10.1128/spectrum.01730-25","DOIUrl":"https://doi.org/10.1128/spectrum.01730-25","url":null,"abstract":"<p><p>Pterygium is a chronic ocular surface condition marked by fibrovascular growth extending from the conjunctiva to the cornea. Emerging evidence suggests that microbial dysbiosis may play a role in its pathogenesis. To elucidate the microbial landscape associated with pterygium, we conducted metagenomic shotgun sequencing on conjunctival sac secretions from 24 patients with pterygium and 23 healthy controls, along with 19 pterygium tissue samples. We observed significantly higher microbial richness in the disease group, with distinct taxonomic profiles compared with healthy and tissue groups. Key species enriched in the disease group included <i>Microbacterium proteolyticum</i> and <i>Bacillus cereus</i>. Functional analyses revealed elevated bacterial motility, chemotaxis, and virulence genes, alongside a notable increase in antibiotic resistance genes such as tetB and AcrAB-TolC. In contrast, pterygium tissue samples showed limited microbial diversity and no detectable virulence or resistance genes. Importantly, the predominance of <i>Vibrio</i> phages in tissue samples, together with the frequent detection of their bacterial host <i>Vibrio diabolicus</i>, suggests a potential region-specific microbial risk factor, particularly relevant in coastal populations. These findings highlight distinct microbiome and functional profiles associated with pterygium, providing new insights into its pathogenesis and possible microbiome-based therapeutic targets.IMPORTANCEUnderstanding how microbial communities contribute to ocular diseases is crucial for advancing both diagnostics and therapy. This study provides the first integrated comparison of healthy ocular surfaces, diseased ocular surfaces, and pterygium tissues, revealing distinct microbial signatures and functional disruptions. The enrichment of specific bacterial taxa, virulence factors, and antibiotic resistance genes in diseased eyes underscores their potential role in shaping local immunity and driving disease progression. Meanwhile, the discovery of distinct viral elements in pterygium tissue expands current understanding of its microecological complexity. These findings lay a theoretical foundation for the development of microbiome-informed diagnostic tools and novel therapeutic interventions for pterygium.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0173025"},"PeriodicalIF":3.8,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}