Frontiers in Cellular and Infection Microbiology最新文献

{"title":"Attenuation of acute kidney injury in a murine model of neonatal <i>Escherichia coli</i> sepsis.","authors":"Esther M Speer, Atilade A Adedeji, Joyce Lin, Alexandra Khorasanchi, Asma Rasheed, Maya Bhat, Kelly Mackenzie, Randolph Hennigar, Kimberly J Reidy, Robert P Woroniecki","doi":"10.3389/fcimb.2024.1507914","DOIUrl":"10.3389/fcimb.2024.1507914","url":null,"abstract":"<p><strong>Introduction: </strong>Sepsis is a risk factor for acute kidney injury (AKI) in neonates, for which no effective treatment exists. The phosphodiesterase inhibitor pentoxifylline (PTX) has demonstrated renal protection from ischemia and inflammation in adult rodents. We hypothesized that addition of PTX to antibiotics may attenuate immune and histological AKI in a murine neonatal sepsis model.</p><p><strong>Methods: </strong>Postnatal (PN) day 1 C57BL/6J mice were injected with <i>E. coli</i> K1 strain at 10⁵ colony forming units per gram weight or saline control. After 1.5 hours, septic pups randomly received saline, gentamicin or cefotaxime, with/without PTX. 5.5h after sepsis initiation, kidneys and blood were harvested for measurements of biomarkers of inflammation and kidney injury. Renal sections from PN7 mice were used for histology and immunofluorescence. Linear mixed effect models were employed to fit the outcomes including interaction between treatment group and sex.</p><p><strong>Results: </strong>Septic mice demonstrated robust expression of pro-inflammatory cytokines, chemokines and biomarkers of tubular injury in renal tissue, which were attenuated in response to combined PTX and antibiotics (gentamicin or cefotaxime): chemokines (p<0.001), plasma (p<0.01) and tissue IL-6 (p<0.05), plasma TNF (p<0.001), NGAL (p<0.01), CXCL10 (p<0.01), osteopontin (p<0.05), and VEGF (p<0.05), with a trend for KIM-1 (tissue concentration: p=0.21, fluorescence area: p=0.12). Interactions between treatment and sex were present for several cytokines and kidney injury biomarkers. Immunofluorescence findings for the tubular injury markers (NGAL and KIM-1) were consistent with biomarker expression in tissue lysates.</p><p><strong>Conclusion: </strong>Neonatal <i>E. coli</i> sepsis leads to increased expression of renal tissue inflammation and injury biomarkers consistent with AKI, which may be attenuated with PTX combined with antibiotic treatment.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1507914"},"PeriodicalIF":4.6,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11830670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440521","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":"Bacterial blood microbiome of <i>Mastomys</i> rodents: implications for disease spill-over at the animal-human interface within the Bushbuckridge-East community, South Africa.","authors":"Agatha O Kolo, Kelly A Brayton, Nicola E Collins, Armanda D S Bastos, Sonja Matthee, Cory A Gall, Jeanette Wentzel, Luis Neves, Marinda C Oosthuizen","doi":"10.3389/fcimb.2025.1520086","DOIUrl":"10.3389/fcimb.2025.1520086","url":null,"abstract":"<p><p>The Bushbuckridge-East community in Mpumalanga Province, South Africa is bordered by nature reserves, including the Manyeleti Game Reserve. Murid rodents are prevalent in both Manyeleti and communal rangelands adjoining the community households. Although rodents are reservoir hosts for a broad range of viral, bacterial and parasitic pathogens, the rodent microbial diversity and transmission of zoonotic agents to humans in the community is understudied. In this study we investigated bacterial diversity in wild and commensal rodents sampled from different habitats. The 16S rRNA gene was amplified from DNA extracted from the blood of 24 wild <i>Mastomys</i> and one <i>Steatomys</i> sp. and subjected to PacBio circular consensus sequencing. As <i>Bartonella</i> species were dominant in the blood microbiome, <i>gltA</i> gene characterization was performed to delineate species. Rodents sampled from peri-urban and communal rangelands had higher proportions of <i>Bartonella</i> spp. [Hlalakahle (77.7%), Gottenburg (47.8%), Tlhavekisa (83.8%)] compared to those from the protected habitat (43.8%). <i>Ehrlichia</i> spp., <i>Anaplasma</i> spp., and <i>Coxiella burnetii</i> were detected at <1% of the sequence reads. Conventional PCR and sequencing validated the detection of <i>Bartonella</i> spp. with the first confirmation of <i>Bartonella mastomydis</i> infection in <i>Mastomys</i> in South Africa. Additionally, 317 mites, 90 fleas, 10 ticks and eight lice were collected from the rodents, providing evidence of possible vectors of the organisms detected. The detection of zoonotic agents in rodents in Bushbuckridge-East community, together with prior serological confirmation of <i>Bartonella</i> and <i>Coxiella</i> in non-malarial acute febrile patients from this community, highlights the possible risks that commensal rodents pose to human health.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1520086"},"PeriodicalIF":4.6,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11830667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439644","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":"Genotype 3 is linked to worse liver disease progression in hepatitis C patients even after SVR following DAA therapy.","authors":"Xiping Ran, Yang Xu, Ying Wang, Cheng Zeng, Chen Gong, Ni Wang, Dachuan Cai","doi":"10.3389/fcimb.2025.1510939","DOIUrl":"10.3389/fcimb.2025.1510939","url":null,"abstract":"<p><strong>Background and aims: </strong>HCV genotype (GT) 3 is associated with rapid liver disease progression. However, the liver disease progression and its risk factors in patients with HCV GT 3 infection after sustained virological response (SVR) following direct-acting antivirals (DAAs) remain unclear. Therefore, we aimed to investigate the liver disease progression of patients with GT 3 after SVR.</p><p><strong>Methods: </strong>This was a retrospective cohort study of patients with HCV infection who achieved SVR by DAAs. The clinical outcome was overall liver disease progression (OLDP), defined as newly diagnosed compensated liver cirrhosis, decompensated liver cirrhosis, or hepatocellular carcinoma. The incidence of OLDP was evaluated by Kaplan-Meier analysis. Cox regression analysis identified the risk factors for OLDP.</p><p><strong>Results: </strong>A total of 409 patients (46.9% GT3) were followed for 43.7 (32.9, 58.7) months. The incidence of OLDP was higher in patients with GT 3 (4.63/100PY) than non-GT 3 (0.60/100PY; P < 0.001). According to Cox multivariate analysis, GT 3 was significantly associated with OLDP (HR 6.41, 95% CI 1.82 - 22.56; P=0.004). The predictors of OLDP in patients with GT 3 were HCV recurrence (HR 12.15, 95% CI 3.18 - 46.46; P < 0.001) and FIB-4 > 3.25 (HR 16.40, 95% CI 1.03 - 39.81; P = 0.046) at baseline.</p><p><strong>Conclusion: </strong>HCV GT 3-infected patients remain at a higher risk of OLDP even after achieving SVR by DAAs, especially patients with advanced liver fibrosis and at high risk for reinfection or virological late relapse.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1510939"},"PeriodicalIF":4.6,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11830654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440143","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":"Risk factors associated with mortality and pathogen characteristics of bloodstream infection-induced severe sepsis in the pediatric intensive care unit: a retrospective cohort study.","authors":"Jian Chen, Haixin Huang, Ruichen Zhang, Yueqiang Fu, Chunmei Jing","doi":"10.3389/fcimb.2025.1492208","DOIUrl":"10.3389/fcimb.2025.1492208","url":null,"abstract":"<p><strong>Background: </strong>Bloodstream infection (BSI)-induced severe sepsis is a common cause of mortality, frequently resulting in septic shock and multiple organ dysfunction syndrome (MODS). This study aimed to analyze mortality risk factors and summarize pathogen characteristics associated with BSI-induced severe sepsis in the pediatric intensive care unit (PICU).</p><p><strong>Methods: </strong>This retrospective study was conducted at a tertiary pediatric hospital between January 2015 and December 2023, encompassing children with BSI-induced severe sepsis in the PICU. Clinical characteristics, laboratory parameters, pathogen characteristics, and drug resistance profiles of the patients were collected. Clinical and laboratory indicators along with pathogen characteristics were summarized. Logistic regression analysis was employed to identify independent risk factors associated with 28-day mortality.</p><p><strong>Results: </strong>A total of 192 patients with bloodstream infection (BSI)-induced severe sepsis were identified, with a 28-day in-hospital mortality rate of 36.98% (71/192). The incidence of septic shock (42.1% <i>vs</i>. 69%, P < 0.001) and AKI (14% <i>vs</i>. 31%, P = 0.005) was significantly lower in the survival group compared to the non-survival group. In multivariate analysis, independent risk factors for 28-day mortality were the pediatric sequential organ failure assessment (pSOFA) score (OR 1.176; 95% CI: 1.046-1.321, <i>p</i> = 0.007) and the P/F value (OR 0.994; 95% CI: 0.991-0.997, <i>P <</i> 0.001). Double organism growth was detected in 8 cultures, and a total of 200 pathogenic bacteria were isolated from all blood cultures. Of these, 110 strains (55.0%) were Gram-negative bacteria, 88 strains (44.0%) were gram-positive bacteria, and 2 strains (1.0%) were <i>Candida albicans</i>. The most commonly isolated pathogens were <i>Staphylococcus aureus, Coagulase-negative Staphylococcus, and Escherichia coli</i>. The detection rate of carbapenem resistance (CR) in <i>Acinetobacter baumannii</i> (66.7%) was higher than that in <i>Pseudomonas aeruginosa</i> (15.4%). The detection rates of extended-spectrum cephalosporin resistance (ECR) and fluoroquinolone resistance (FQR) in <i>Escherichia coli</i> (<i>E. coli</i>) were higher than those in <i>Klebsiella pneumoniae</i>.</p><p><strong>Conclusion: </strong>In the PICU, higher mortality was observed in children with BSI-induced severe sepsis who presented with elevated pSOFA scores and low P/F values. <i>Acinetobacter baumannii</i> exhibited the highest levels of CR and FQR, while <i>Escherichia coli</i> demonstrated the highest level of ECR.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1492208"},"PeriodicalIF":4.6,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11830655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440435","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":"Transcriptome analysis reveals the molecular mechanism of γ-linolenic acid eradicating the biofilm of vancomycin-resistant <i>Enterococcus faecium</i>.","authors":"Ming Wei, Peng Wang, Tianmeng Li, Jun Liu, Yu Wang, Li Gu, Shuai Wang","doi":"10.3389/fcimb.2025.1525581","DOIUrl":"10.3389/fcimb.2025.1525581","url":null,"abstract":"<p><strong>Introduction: </strong>Vancomycin-resistant <i>Enterococcus faecium</i> (VRE-fm) biofilms pose a significant clinical challenge due to the limited effectiveness of traditional antibiotics. This study investigates the potential of γ-linolenic acid (GLA) as a novel antibiofilm agent.</p><p><strong>Methods: </strong>Transcriptome analysis was performed on the V27 isolate, comparing cells in mature biofilms treated with and without GLA. The findings were further validated using qRT-PCR on six VRE-fm isolates and two <i>E. faecalis</i> isolates.</p><p><strong>Results: </strong>Transcriptome analysis revealed a significant downregulation in the expression levels of genes associated with biofilm formation, including <i>fruA</i>, <i>fruB</i>, <i>sgrA</i>, <i>lpxtg-cwa</i>, <i>tfpp</i>, <i>lafA</i>, <i>lafB</i>, <i>malP</i>, <i>fsrA</i>, and <i>fsrC'</i>, while a significant upregulation was observed in the expression of <i>fsrBD</i>. Validation by qRT-PCR in six VRE-fm isolates confirmed the significant changes in the expression levels of all genes except for <i>lpxtg-cwa</i>, with statistical significance. The expression of <i>bgsB</i> and <i>bgsA</i> genes, which are the homologs of <i>lafA</i> and <i>lafB</i> genes, along with the Fsr-regulated genes <i>gelE</i> and <i>sprE</i> in <i>E. faecalis</i>, were also found to be downregulated by GLA. In addition, KEGG analysis identified specific metabolic pathways that were significantly downregulated by GLA.</p><p><strong>Conclusion: </strong>GLA effectively targets multiple aspects of biofilm formation in VRE-fm, including the downregulation of key biofilm-related genes, the inhibition of quorum sensing systems, and the modulation of metabolic pathways. GLA emerges as a promising candidate for eradicating <i>Enterococcus</i> biofilms.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1525581"},"PeriodicalIF":4.6,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11826239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432634","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":"Targeted next-generation sequencing for antimicrobial resistance detection in ventilator-associated pneumonia.","authors":"Yuting Li, Yanfang Jiang, Hao Liu, Yao Fu, Junying Lu, Hongyan Li, Lulu Sheng, Dejian Gu, Dong Zhang","doi":"10.3389/fcimb.2025.1526087","DOIUrl":"10.3389/fcimb.2025.1526087","url":null,"abstract":"<p><strong>Background: </strong>Ventilator-associated pneumonia (VAP) carries a high mortality rate in the intensive care units (ICUs) due to its widespread drug resistance. Traditional microbial cultures limited by speed and sensitivity, are often unable to help clinicians make effective diagnosis and treatment. Therefore, there is an urgent need for a rapid and accurate test that can identify both pathogens and their antimicrobial resistance (AMR) to improve the prognosis of patients with VAP.</p><p><strong>Study design: </strong>We analyzed samples from ICU patients with suspected VAP using both microbial tests and targeted next-generation sequencing (tNGS), comparing the results of tNGS pathogen and AMR detection against microbial culture and antimicrobial susceptibility testing (AST).</p><p><strong>Results: </strong>Involving 199 patients with suspected VAP, tNGS showed a sensitivity rate of 98.98% for pathogen identification. While the sensitivity rate of microbial culture was just 66.84%. Additionally, tNGS performed almost half the turnaround time of microbial culture (1.66 days vs 3.00 days). For AMR, the overall consistency between AST and tNGS was 79.31%. The great performance particularly exhibited for <i>Acinetobacter baumannii</i> carbapenem-penicillin-cephamycin resistance.</p><p><strong>Conclusion: </strong>tNGS excels in identifying pathogens and AMR. Its rapid workflow makes it ideal for managing critically ill patients, enhancing treatment precision, and reducing antibiotic misuse.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1526087"},"PeriodicalIF":4.6,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432524","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":"BTS1-knockout <i>Saccharomyces cerevisiae</i> with broad-spectrum antimicrobial activity through lactic acid accumulation.","authors":"Liu Cong, Yuan Zhou, Yu Zhang, Shanshan Mao, Chaoqun Chen, Liying Wang, Xiao Li, Zuo Zhang, Zuobin Zhu, Ying Li","doi":"10.3389/fcimb.2025.1494149","DOIUrl":"10.3389/fcimb.2025.1494149","url":null,"abstract":"<p><p>Bacterial infections pose significant threats to human health, and prudent antibiotic use remains a key strategy for disease treatment and control. However, a global escalation of drug resistance among pathogenic bacteria presents a formidable challenge. Probiotics have emerged as a promising approach to combating pathogenic bacterial infections. In this study, we investigated the antibacterial activity of BTS1-knockout (BTS1-KO) <i>Saccharomyces cerevisiae</i>. Our findings demonstrate its effective inhibition of pathogen growth as evidenced by Minimum inhibitory concentration (MIC) assays, growth curves, bacteriostatic spectrum analyses and co-culture experiments. Additionally, it significantly impedes <i>Escherichia coli</i> and <i>Staphylococcus aureus</i> biofilm formation. Moreover, BTS1-KO <i>S. cerevisiae</i> exhibits low haemolytic activity, acid resistance, resistance to high bile salt concentrations, high auto-aggregation capacity and high co-aggregation capacities with pathogenic bacteria. Moreover, infected larvae treated with BTS1-KO <i>S. cerevisiae</i> in <i>Galleria mellonella</i>-<i>E. coli</i> (<i>in vivo</i>) and <i>G. mellonella</i>-<i>S. aureus</i> (<i>in vivo</i>) infection models showed significantly prolonged survival times. Mechanistic investigations revealed that BTS1-KO <i>S. cerevisiae</i> primarily produced lactic acid via metabolism, thereby lowering the environmental pH and inhibiting pathogenic bacterial growth. In summary, our study underscores the probiotic potential of BTS1-KO <i>S. cerevisiae</i>, offering broad-spectrum antibacterial activity <i>in vitro</i> and <i>in vivo</i> with low toxicity. This highlights BTS1-KO <i>S. cerevisiae</i> as a promising probiotic candidate for clinical prevention and control of bacterial infection.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1494149"},"PeriodicalIF":4.6,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432254","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 epidemiology and antimicrobial resistance of <i>Morganella</i> clinical isolates between 2016 and 2023.","authors":"Wentao Zhu, Qian Liu, Jinlv Liu, Yaqi Wang, Hong Shen, Ming Wei, Ji Pu, Li Gu, Jing Yang","doi":"10.3389/fcimb.2024.1464736","DOIUrl":"10.3389/fcimb.2024.1464736","url":null,"abstract":"<p><p><i>Morganella morganii</i> is a Gram-negative, opportunistic pathogen that is often associated with nosocomial infections. Here, the genomic characteristics and antimicrobial resistance (AMR) of <i>Morganella</i> clinical isolates between 2016 and 2023 were determined. A total of 218 clinical isolates were mainly identified from urinary tract (48.2%) and respiratory tract (16.5%), with 105 isolates randomly selected for whole genome sequencing. The highest rates of antibiotic resistance were observed with SAM (68.3%), followed by CIP (39.9%), and SXT (37.2%). Distance analysis suggested that the 105 newly sequenced isolates could be divided into two groups: <i>M. morganii</i> subsp. <i>morganii</i> and <i>M. morganii</i> subsp. <i>sibonii</i>. While, the average nucleotide identity between these groups showed only 91.5-92.2% similarity, raising the possibility that they may be distinct species. Phylogenomic analysis revealed that the 102 <i>M. morganii</i> isolates fell into six clades, with clades 4-6 making up the majority. Core genome multi-locus sequence type analysis indicted high genomic diversity among different hosts and relatively stability (< 10 SNPs accumulated over three years) within the same host. Together with epidemiological data, isolates of four genetic clusters could be possible nosocomial transmissions. The identified 80 AMR genes belonged to 15 drug-related classes, with <i>tet(B)</i> gene being the most prevalent, followed by <i>sul1</i>, <i>catA2</i>, and <i>sul2</i> genes. This study provided comprehensive genomic insights and AMR patterns of <i>Morganella</i> isolates in China, highlighting the necessity for continuous monitoring through whole genome sequencing.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1464736"},"PeriodicalIF":4.6,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11826060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432862","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":"Temporal and spatial characterization of keratinocytes supporting orf virus replication.","authors":"Byung-Joon Seung, Sushil Khatiwada, Daniel L Rock, Gustavo Delhon","doi":"10.3389/fcimb.2024.1486778","DOIUrl":"10.3389/fcimb.2024.1486778","url":null,"abstract":"<p><p>Reflecting their tropism for keratinocytes, most poxviruses that infect vertebrates replicate to high titers and cause pathology in the skin. Keratinocytes, the main cells of the epidermis, are found in different stages of a differentiation program that produces the critical barrier against environmental damage. While systemic poxviruses (e.g. smallpox virus, sheeppox virus) also infect other cell types, the parapoxvirus orf virus (ORFV), which causes localized infections in sheep and goats, has not been shown to replicate in cells other than keratinocytes. Notably, ORFV infection only occurs after or concomitant with epidermal damage and the subsequent healing response and shows unexplained delayed virus replication in an uncharacterized keratinocyte subpopulation. Using <i>in situ</i> hybridization, immunohistochemistry, confocal microscopy, qPCR, and a full-thickness wound/infection model in sheep, the natural host, we show that during an initial 2-day eclipse phase viral transcription and viral DNA replication are not detected. Between days 2 and 3 pi, viral transcription is first detected in keratinocytes of the stratum granulosum and upper stratum spinosum in the proliferative zone at the wound margin. These cells are positive for cytokeratin 10, a suprabasal marker; cytokeratin 6, a protein induced during early repair responses; stratum granulosum markers filaggrin and loricrin; and negative for the nuclear proliferation marker Ki-67 and cytokeratin 14, a basal cell marker. This marker profile suggests that keratinocytes supportive of viral replication are engaged in advanced keratinocyte differentiation rather than proliferation.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1486778"},"PeriodicalIF":4.6,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432874","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":"A novel strategy for eradication of staphylococcal biofilms using blood clots.","authors":"Kayla E Grooters, Sheridan L Hayes, David M Richter, Jennifer C Ku, Robert Sawyer, Yong Li","doi":"10.3389/fcimb.2025.1507486","DOIUrl":"10.3389/fcimb.2025.1507486","url":null,"abstract":"<p><strong>Introduction: </strong>Infections with coagulase negative staphylococcal species (CoNS) are a major cause of mortality and morbidity in joint and heart valve replacement procedures, largely due to biofilm formation. Cells within biofilms have higher rates of antibiotic resistance than their planktonic counterparts; consequently, novel mechanisms are needed to combat these infections.</p><p><strong>Methods: </strong>To enhance antibiotic delivery and penetration, this innovative study involved treating CoNS biofilms with murine blood clots impregnated with antibiotics. We then investigated the impact of this treatment on biofilm density, metabolism, and architecture.</p><p><strong>Results: </strong>Our pilot study demonstrates that this method of antibiotic delivery results in improved biofilm clearance, relative to conventional exposure methods.</p><p><strong>Discussion: </strong>Our results demonstrate that blood clot exposure has an intrinsic impact on biofilm density and potentially reduces colonization, warrenting further investigation into the mechanism.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1507486"},"PeriodicalIF":4.6,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11827428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432876","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}