{"title":"A strain defined as a novel species in the <i>Acinetobacter</i> genus co-harboring chromosomal associated <i>tet</i>(X3) and plasmid associated <i>bla</i> <sub>NDM-1</sub> from a beef cattle farm in Hebei, China.","authors":"Qing Wang, Yanming Wei, Muhammad Shoaib, Yanhua Qiu, Chao Zhang, Guonian Dai, Honglin Lin, Weiwei Wang, Jiyu Zhang","doi":"10.3389/fcimb.2025.1594982","DOIUrl":"10.3389/fcimb.2025.1594982","url":null,"abstract":"<p><strong>Introduction: </strong>The co-existence phenomenon of antibiotic resistance genes (ARGs), particularly of last-resort antibiotics in multi-drug resistant (MDR) bacteria, is of particular concern in the least studied bacterial species.</p><p><strong>Methods: </strong>In 2023, strain M2 was isolated from the sludge sample at a commercial bovine farm in Hebei province, China, using a MacConkey plate containing meropenem. PCR amplification and Sanger sequencing verified it co-carrying <i>bla</i> <sub>NDM</sub> and <i>tet</i>(X) genes. It was classified within the Acinetobacter genus by MALDI-TOF-MS and 16S rDNA analyses. Whole-genome sequencing (WGS) was performed on the Oxford Nanopore platform, with species-level identification via ANI and dDDH. Antimicrobial susceptibility testing was performed against 20 antibiotics. Conjugation assays employed the filter-mating method using <i>E. coli</i> J53 and <i>Salmonella</i> LGJ2 as recipients.</p><p><strong>Results: </strong>This strain was confirmed as a novel species of <i>Acinetobacter</i> genus, showing resistance to meropenem, ampicillin, ceftazidime, cefepime, gentamicin, kanamycin, fosfomycin, imipenem, ertapenem, and tetracycline. Despite carrying <i>tet</i>(X3), it remained susceptible to tigecycline, omadacycline, and doxycycline. The genome carried 11 ARG types, multiple metal resistance genes (MRGs), and virulence factor (VF) genes. The <i>bla</i> <sub>NDM-1</sub> was located in a skeleton, IS<i>Aba125-bla</i> <sub>NDM-1</sub>-<i>ble</i> <sub>MBL</sub>-<i>trpF</i>, which was carried by an IS<i>Aba</i>14-mediated rolling-circle-like structure in pM2-2-NDM-1 (rep_cluster_481). Integrative and conjugative element (ICE) and multiple pd<i>if</i> modules (driven by the XerCD site-specific recombination (XerCD SSR) system), which were associated with the mobilization of resistance determinants, were identified in this plasmid. Chromosomal <i>tet</i>(X3) was mediated by IS<i>Vsa3</i>, forming a skeleton, IS<i>Vsa3-XerD-tet</i> (X3)<i>-res-ISVsa3</i>.</p><p><strong>Discussion: </strong>The co-occurrence of <i>bla</i> <sub>NDM</sub> and <i>tet</i>(X) in a novel species of the <i>Acinetobacter</i> genus hints that substantial undiscovered bacteria co-carrying high-risk ARGs are concealing in the agroecological system, which should cause particular concern.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1594982"},"PeriodicalIF":4.6,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12263697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648947","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}
Felix Schweitzer, Lara-Jasmin Schröder, Alina Friedrichs, Viktoria Gudi, Thomas Skripuletz, Imke Steffen, Martin Palus, Daniel Růžek, Albert Osterhaus, Chittappen Kandiyil Prajeeth
{"title":"Mosquito- and tick-borne orthoflaviviruses cross an <i>in vitro</i> endothelial-astrocyte barrier.","authors":"Felix Schweitzer, Lara-Jasmin Schröder, Alina Friedrichs, Viktoria Gudi, Thomas Skripuletz, Imke Steffen, Martin Palus, Daniel Růžek, Albert Osterhaus, Chittappen Kandiyil Prajeeth","doi":"10.3389/fcimb.2025.1624636","DOIUrl":"10.3389/fcimb.2025.1624636","url":null,"abstract":"<p><strong>Introduction: </strong>The genus <i>Orthoflavivirus</i> of the <i>Flaviviridae</i> family includes several notable pathogens such as mosquito-borne West-Nile virus (<i>Orthoflavivirus nilense</i>, WNV) and Tick-borne encephalitis virus (<i>Orthoflavivirus encephalitidis</i>, TBEV) that are highly neurotropic and may cause severe neurological disease leading to lifelong disabilities, coma and death. These viruses have developed mechanisms to breach the compact blood-brain barrier (BBB) and establish infection within the central nervous system (CNS). Nevertheless, neuroinvasive mechanisms of orthoflaviviruses remain poorly understood. Complex anatomy of the CNS and the organization of the BBB is a major challenge to study neuroinvasion of orthoflaviviruses <i>in vivo</i>. Therefore, <i>in vitro</i> BBB models are useful tools to study direct interaction of viruses with the endothelial barrier.</p><p><strong>Methods: </strong>In this study, we employed an <i>in vitro</i> transwell BBB model comprising primary mouse brain microvascular endothelial cells and astrocytes to compare the ability of mosquito-borne and tick-borne orthoflaviviruses to cross a compact endothelial barrier and reach the basolateral compartment of the transwell system. The influence of virus inoculation on the barrier properties was determined by measuring transendothelial electrical resistance (TEER).</p><p><strong>Results: </strong>The results demonstrate that while pathogenic WNV and TBEV cross the endothelial barrier the ability of low pathogenic Usutu virus (USUV) and Langat virus (LGTV) was inconsistent. All viruses tested display virus replication within the endothelial cells. Nevertheless, virus replication did not affect the barrier function of endothelial cells as demonstrated by sustained TEER and absence of leakage of high molecular weight dextran molecules through the endothelial barrier even at several hours post infection.</p><p><strong>Discussion: </strong>Our findings indicate that orthoflaviviruses can infect the endothelial cells, replicate within them without affecting the cells and its barrier function. Nevertheless, only pathogenic WNV and TBEV showed the ability to cross the endothelial barrier and reach the basolateral compartment.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1624636"},"PeriodicalIF":4.6,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12263646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648949","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}
Marla Keizers, Krishnendu Mukherjee, Michael Berger, Ulrich Dobrindt
{"title":"Less is more: the lack of autoinducer-2-dependent quorum sensing promotes competitive fitness of <i>Escherichia coli</i> strain 83972.","authors":"Marla Keizers, Krishnendu Mukherjee, Michael Berger, Ulrich Dobrindt","doi":"10.3389/fcimb.2025.1603759","DOIUrl":"10.3389/fcimb.2025.1603759","url":null,"abstract":"<p><p>Autoinducer-2 is a signaling molecule involved in quorum sensing in <i>Escherichia coli</i>. Quorum sensing enables coordinated behavior based on cell density and helps bacteria adapt to their environment. The <i>luxS</i> gene and the <i>lsr</i> locus are involved in the biosynthesis, transport, and intracellular phosphorylation of autoinducer-2. Disruption of autoinducer-2 biosynthesis or transport can reduce biofilm formation, chemotaxis, and the expression of genes relevant for the uropathogenicity of <i>E. coli</i>. Interestingly, most isolates of <i>E. coli</i> phylogroup B2, in which uropathogenic and other extraintestinal pathogenic strains are overrepresented, lack the <i>lsr</i> operon. We show that autoinducer-2-dependent quorum sensing is not fundamentally beneficial for efficient and prolonged urinary bladder colonization. We demonstrate that the <i>lsr</i>-negative asymptomatic bacteriuria isolate 83972 has a higher fitness than its <i>lsr</i>-complemented variant. Using transcriptome analyses, competitive growth assays, and comparisons of selected fitness properties, we show that restoration of the <i>lsr</i> operon in this strain background results in growth retardation, loss of competitiveness, and higher sensitivity to oxidative stress. Our results illustrate that the lack of autoinducer-2-dependent quorum sensing contributes to the well-known fitness and competitiveness of <i>E. coli</i> 83972, on which its effective use for bacterial interference in the urinary bladder relies. It is vital to delve deeper to fully understand the fitness and competitiveness of the ABU strain 83972 if we are to optimize its use in therapeutic colonization. The key is to unravel the underlying molecular mechanisms, thus ensuring the efficacy and safety of this treatment as an alternative to antibiotic therapy.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1603759"},"PeriodicalIF":4.6,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12263705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648948","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":"The role of probiotics in adolescents' obesity.","authors":"Xiao-Ping Chen, Li You, Yong Jia","doi":"10.3389/fcimb.2025.1546627","DOIUrl":"10.3389/fcimb.2025.1546627","url":null,"abstract":"<p><p>The prevalence of adolescent obesity continues to rise globally, posing significant public health challenges by affecting both physical and psychological wellness and increasing the risk of metabolic diseases in adulthood. Probiotics may influence obesity through various mechanisms, including restoring gut microbiota balance, reducing chronic inflammation, modulating lipid metabolism, aiding in weight control, and improving metabolic health. This review aims to explore the mechanisms by which probiotics act as key modulators of obesity and summarize current findings from clinical trials involving probiotics in adolescent obesity. The large-scale, multicenter, long-term follow-up randomized controlled trials are necessary to determine the optimal probiotics strains, dosages, and treatment durations, as well as to assess their long-term efficacy and safety in the future. Through such rigorous studies, probiotics have the potential to become a safe, effective, and accessible adjunct in the comprehensive management of adolescent obesity, offering a more holistic approach to health management for this population.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1546627"},"PeriodicalIF":4.6,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12263623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648950","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}
Amir Hossein Barjasteh, Hanieh Latifi, Ali Sepehrinezhad
{"title":"A bioinformatic analysis to systematically unveil shared pathways and molecular mechanisms underlying monkeypox and its predominant neurological manifestations.","authors":"Amir Hossein Barjasteh, Hanieh Latifi, Ali Sepehrinezhad","doi":"10.3389/fcimb.2025.1506687","DOIUrl":"10.3389/fcimb.2025.1506687","url":null,"abstract":"<p><strong>Background: </strong>Monkeypox (MPOX) is a zoonotic disease caused by the MPOX virus (MPXV). MPOX resurfaced globally in May 2022, spreading throughout six WHO regions, resulting in nearly 87,000 cases and 112 deaths. Clinical symptoms include swollen lymph nodes, fever, joint pain and several neurological complications such as headache, encephalitis, myalgia, fatigue, photophobia and seizures. Despite these manifestations, the precise mechanisms of MPXV's neurotropism remain elusive. This study aimed to explore the genetic underpinnings of MPOX-related neurological manifestations, including headache, myalgia, fatigue, and photophobia, using advanced bioinformatics tools.</p><p><strong>Methods: </strong>Data were sourced from the GeneCards database, which is an integrated database of human genes. Genes linked to MPOX and its neurological manifestations were identified and cross-referenced to uncover shared genes between these conditions. Network visualization was created using STRING, followed by topological analysis in Cytoscape to identify key genes based on degree and betweenness centrality. Functional enrichment analysis through ToppGene provided insights into molecular functions, biological processes, and cellular components associated with these target genes. Pathway analysis was performed using WikiPathways, and cell-type-specific enrichment was conducted using Enrichr. Additionally, we predicted functional microRNAs using mirTarbase and identified potential drug candidates via the Stitch database.</p><p><strong>Results: </strong>We identified 32 MPOX-associated genes and a large set of neurological manifestation-related genes. Ten hub genes, including CD55, CXCL1, NFKB1, CXCL8, CD4, IL6, MX1, CFH, KLRK1, and CD46 were shared between MPOX and its neurological manifestations. Five novel genes, including CFHR3, C5AR1, C3AR1, IFNA2, and CXCL3 were predicted to be associated with MPOX and its neurological complications. Gene ontology analysis highlighted biological processes such as immune regulation, viral life cycle, and lymphocyte activation, while pathway enrichment identified critical signaling mechanisms like prostaglandin signaling, toll-like receptor 4 (TLR4) signaling, complement activation, and neuroinflammation. Moreover, cell types such as T-helper cells, natural killer cells, and microglia were found to be significantly impacted by MPOX and its frequent neurological complications. We identified 11 key microRNAs associated with MPOX-neurological manifestations and repurposed eight potential drugs, offering promising therapeutic strategies.</p><p><strong>Conclusion: </strong>This study emphasizes the central role of the complement system, immunological responses, and inflammatory pathways in the neurological manifestations of MPOX. The identification of novel genes and predicted therapeutic targets paves the way for future research and therapeutic interventions. Experimental validation is required to confirm these finding","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1506687"},"PeriodicalIF":4.6,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12263605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648946","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}
Zeinab El Zein, Celina F Boutros, Marwa El Masri, Elsy El Tawil, Maher Sraj, Yara Salameh, Sarah Ghadban, Rim Salameh, Silma El Baasiri, Amani Haddara, Mayse Nasser, Shady Tabbara, Sarah Khafaja, Rawan Korman, Soha Ghanem, Dany Al Hamod, Ghassan S Dbaibo
{"title":"The challenge of multidrug resistance in hospitalized pediatric patients with urinary tract infections.","authors":"Zeinab El Zein, Celina F Boutros, Marwa El Masri, Elsy El Tawil, Maher Sraj, Yara Salameh, Sarah Ghadban, Rim Salameh, Silma El Baasiri, Amani Haddara, Mayse Nasser, Shady Tabbara, Sarah Khafaja, Rawan Korman, Soha Ghanem, Dany Al Hamod, Ghassan S Dbaibo","doi":"10.3389/fcimb.2025.1570405","DOIUrl":"10.3389/fcimb.2025.1570405","url":null,"abstract":"<p><strong>Background: </strong>The choice of empirical treatment in pediatric urinary tract infections (UTIs) is increasingly complicated by the emergence of antibiotic resistance and the growing prevalence of multidrug-resistant organisms (MDROs). The aim of this study is to assess the resistance patterns of isolated uropathogens among children and adolescents hospitalized with UTIs in Lebanon; and determine the risk factors associated with MDRO-related UTIs over a 10-year period.</p><p><strong>Methods: </strong>A retrospective chart review was conducted at two tertiary medical centers in Beirut. Children and adolescents less than 18 years who were admitted, between January 1, 2011, and December 31, 2021, with the following ICD-10 codes: \"urinary tract infection\", \"cystitis\" and/or \"pyelonephritis \" were included. A case was excluded if the urine culture was polymicrobial or did not meet the definition of UTI we used. Univariate and multivariable logistic regression analyses were performed to identify risk factors for MDRO infections.</p><p><strong>Results: </strong>Among the 876 pediatric UTI cases included, 85% were above 2 months of age and 74.1% were females. 64.5% of 644 <i>Escherichia coli</i> and 61.9% of 114 <i>Klebsiella</i> spp. isolates met international MDR criteria. After a period of fluctuation, the proportion of MDROs began to steadily increase starting 2019 eventually surpassing the 2011 percentage by nearly 10% in 2021 (67.9%, <i>p</i> = 0.248). Only 2.1% of MDR <i>E. coli</i> and 2.9% of MDR <i>Klebsiella</i> spp. were resistant to carbapenems. However, aminoglycoside resistance was high ranging between 28.3% and 48.6%. Children aged ≥ 5 years were nearly twice as likely to present with an MDR uropathogen compared to those < 5 years of age (<i>p</i> < 0.001). Only a history of leukemia (<i>p</i> = 0.010, AOR = 4.248, 95% CI [1.412-12.778]) and antibiotic use in the preceding 30 days (<i>p</i> = 0.012, AOR = 2.045, 95% CI [1.167-3.582]) were found as independent risk factors for UTIs caused by MDROs in multivariable logistic regression.</p><p><strong>Conclusion: </strong>This study highlights the increasing threat of MDROs among pediatric UTIs. Recent antibiotic use was strongly associated with MDRO infections highlighting the urgent need for effective antimicrobial stewardship, re-evaluation of empiric treatment guidelines, and strict abidance by infection control measures.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1570405"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12259619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642247","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}
Siyu Chen, Haiying Li, Mengyang Guo, Hua Wang, Wei Gao, Yating Cui, Yani Zhang, Lin Yuan, Wei Shi, Kaihu Yao
{"title":"A single-center investigation on serotypes, drug resistance and clinical significance of GBS isolates from pregnant and non-pregnant adults in Baoji, China.","authors":"Siyu Chen, Haiying Li, Mengyang Guo, Hua Wang, Wei Gao, Yating Cui, Yani Zhang, Lin Yuan, Wei Shi, Kaihu Yao","doi":"10.3389/fcimb.2025.1556603","DOIUrl":"10.3389/fcimb.2025.1556603","url":null,"abstract":"<p><strong>Objectives: </strong>To assess the epidemiology, serotype distribution, and antimicrobial resistance of GBS among both pregnant and non-pregnant adults in Baoji, China, addressing an existing gap in current research.</p><p><strong>Methods: </strong>Based on the GBS strains identified in the clinical laboratory from 2016 to 2024, information on age, gender, specimen type, and diagnosis was collected for the corresponding adult cases, including both colonization and infection cases. GBS was identified using three methods: mass spectrometry, CAMP test and latex agglutination kit for streptococcal serotyping. Serotypes were determined by latex agglutination, and antimicrobial susceptibility was tested against 20 antimicrobials using an automated drug susceptibility system.</p><p><strong>Results: </strong>A total of 200 GBS strains were collected, in which 107 were from pregnant women, and 93 from non-pregnant adults including 34 males. Clinical pathogenic isolates were defined for 86 cases, in which the urinary tract infections were predominant (61.6%), and invasive infections were confirmed for 16 cases (18.6%). A total of 5 serotypes were identified in the present 200 strains, including serotype Ib (34.5%), V (26.0%), III (21.5%), Ia (2.0%) and VIII (1.0%). In addition, 30 strains (15.0%) were non-typeable (NT). The coverage rate of the hexavalent vaccine currently in development is 84.5%. Significant differences are observed in the proportions of serotypes Ib, III, and/or V across various age groups, pregnancy statuses, and between colonized and infectious strains. Notably, the proportion of serotype V varies markedly, with 32.3% in the 18-39 age group versus 18.9% in the 40-64 age group and 10% in the >64 age group, 36.4% in pregnant women compared to 14.0% in non-pregnant women, and 34.2% in colonized strains as opposed to 15.1% in infectious ones. All 200 GBS strains were sensitive to penicillin, and the resistance rates to erythromycin, azithromycin, levofloxacin, clindamycin, tetracycline, and chloramphenicol were 93.5%, 93.5%, 70.5%, 70.0%, 53.5%, and 13.0%, respectively.</p><p><strong>Conclusion: </strong>The present findings suggest that GBS may potentially infect and colonize adults, regardless of gender or age, in Baoji, China. Serotypes Ib, III, and V are common serotypes, but their frequency is related to the host's age group, pregnancy status, and clinical relevance. GBS isolates are still generally susceptible to penicillin.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1556603"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12259621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642234","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}
Macarena Orejudo, Manuel J Gómez, Sabino Riestra, Montserrat Rivero, Ana Gutiérrez, Iago Rodríguez-Lago, Luis Fernández-Salazar, Daniel Ceballos, José Manuel Benítez, Mariam Aguas, Iria Bastón-Rey, Fernando Bermejo, María José Casanova, Rufo H Lorente-Poyatos, Yolanda Ber, Daniel Ginard, María Esteve, Ruth de Francisco, María José García, Rubén Francés, Ainhoa Rodríguez, Noelia Alcaide Suárez, Elena Guerra Del Río, Pilar Soto, Pilar Nos, Manuel Barreiro-de Acosta, Iván Guerra, Daniel Hervías Cruz, Manuel Domínguez Cajal, Vanesa Royo, Montserrat Aceituno, Laila Aldars-García, Ana Garre, Cristina Ramírez, Irene Soleto, Ina Schuppe-Koistinen, Lars Engstrand, Montse Baldán-Martín, Fátima Sánchez-Cabo, Javier P Gisbert, María Chaparro
{"title":"Exploration of fecal microbiota in newly diagnosed patients with inflammatory bowel disease using shotgun metagenomics.","authors":"Macarena Orejudo, Manuel J Gómez, Sabino Riestra, Montserrat Rivero, Ana Gutiérrez, Iago Rodríguez-Lago, Luis Fernández-Salazar, Daniel Ceballos, José Manuel Benítez, Mariam Aguas, Iria Bastón-Rey, Fernando Bermejo, María José Casanova, Rufo H Lorente-Poyatos, Yolanda Ber, Daniel Ginard, María Esteve, Ruth de Francisco, María José García, Rubén Francés, Ainhoa Rodríguez, Noelia Alcaide Suárez, Elena Guerra Del Río, Pilar Soto, Pilar Nos, Manuel Barreiro-de Acosta, Iván Guerra, Daniel Hervías Cruz, Manuel Domínguez Cajal, Vanesa Royo, Montserrat Aceituno, Laila Aldars-García, Ana Garre, Cristina Ramírez, Irene Soleto, Ina Schuppe-Koistinen, Lars Engstrand, Montse Baldán-Martín, Fátima Sánchez-Cabo, Javier P Gisbert, María Chaparro","doi":"10.3389/fcimb.2025.1595884","DOIUrl":"10.3389/fcimb.2025.1595884","url":null,"abstract":"<p><strong>Introduction: </strong>Dysbiosis is a key mechanism in inflammatory bowel disease (IBD) pathophysiology. Previous microbiota studies in IBD generally have involved patients treated with immunosuppressive agents, which can affect the results. We aimed to elucidate the fecal microbiota composition in newly diagnosed treatment-naïve IBD patients.</p><p><strong>Methods: </strong>Microbiota from stool samples were investigated using shotgun metagenomics sequencing and subsequent bioinformatics analysis.</p><p><strong>Results: </strong>A total of 103 patients with Crohn's disease (CD), 144 with ulcerative colitis (UC), and 49 healthy controls (HC) were included. CD patients had significantly lower species-level diversity than those with UC and HC. CD subgroups with Ileocolonic location and stricturing behavior showed reduced diversity compared to HC. A negative correlation was observed between endoscopic severity and microbial diversity in CD patients. UC patients had similar microbial diversity to HC, which was unaffected by disease activity. Taxonomic abundance analysis revealed a tendency towards a higher relative abundance of Escherichia coli and a lower relative abundance of Faecalibacterium prausnitzii in IBD patients compared to HC. However, the most significant differences in these patients compared to HC were observed in less abundant species, such as Toxoplasma gondii, Gemella morbillorum, and several species of the Adlercreutzia genera. Functional analysis in these patients highlighted changes in carbohydrate and nucleotide pathways.</p><p><strong>Discussion: </strong>Our data suggest that newly diagnosed CD patients show significant microbiota composition disparities compared to UC patients and HC. Microbiota differences in these patients are linked to dysbiosis, characterized by a reduction in beneficial genera such as Gemella and Adlercreutzia, and a rise in pathogenic species.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1595884"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12259665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642246","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}
Xue Zhang, Shulan Sun, Siqi Cheng, Junze Dai, Furong Du, Jingrui Wang, Dan Wei, Yichao Yan, Yefu Liu
{"title":"Coculture of tumor organoids with pathogenic microorganisms: a novel system to mimic <i>in vivo</i> pathogenic infection.","authors":"Xue Zhang, Shulan Sun, Siqi Cheng, Junze Dai, Furong Du, Jingrui Wang, Dan Wei, Yichao Yan, Yefu Liu","doi":"10.3389/fcimb.2025.1601688","DOIUrl":"10.3389/fcimb.2025.1601688","url":null,"abstract":"<p><p>Since the early 20<sup>th</sup> century, there has been extensive discussion on the intricate relationship between pathogenic infection and tumors. However, most studies on host-pathogen interactions are performed based on the <i>in-vitro</i> culture, immortalized cell lines or animal experiments. A significant challenge lies in accurately establishing a coculture model between tumors and pathogens under the three-dimensional (3D) context. Recently, the hybrid model system that incorporates 3D tumor organoids and two-dimensional cell lines have been gradually used to analyze the intricate relationship between pathogens and tumors, and several coculture techniques for tumor organoids and pathogens have also been developed. Therefore, this study systematically reviewed the preparation and identification of tumor organoids, coculture techniques with pathogens, and their clinical applications, aiming to further understand and simulate the interaction mechanism between the hosts and pathogens.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1601688"},"PeriodicalIF":4.6,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12256518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636608","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}
Marte Glambek, Morten Kjos, Marita T Mårli, Zhian Salehian, Steinar Skrede, Audun Sivertsen, Bård R Kittang, Oddvar Oppegaard
{"title":"<i>TrexAB</i>, a novel tetracycline resistance determinant in <i>Streptococcus dysgalactiae</i>.","authors":"Marte Glambek, Morten Kjos, Marita T Mårli, Zhian Salehian, Steinar Skrede, Audun Sivertsen, Bård R Kittang, Oddvar Oppegaard","doi":"10.3389/fcimb.2025.1583926","DOIUrl":"10.3389/fcimb.2025.1583926","url":null,"abstract":"<p><strong>Background: </strong><i>Streptococcus dysgalactiae</i> (SD) is a potent pathogen associated with infections in a broad range of host species. Notably, a substantial proportion of SD isolates exhibit reduced susceptibility to tetracycline but lack identifiable resistance determinants. In the present study, we wanted to explore the genetic basis for this low-grade resistance to tetracycline.</p><p><strong>Methods: </strong>Genome-wide association studies were performed on a collection of 407 SD genomes to identify potential novel resistance determinants. Two strains of SD, belonging to each of the subspecies <i>dysgalactiae</i> and <i>equisimilis</i> were used for mutagenesis. Natural transformation was exploited to knock out resistance gene candidates, and the resultant mutants were compared with their respective wildtypes regarding susceptibility to tetracycline, doxycycline, minocycline, tigecycline, erythromycin, gentamicin, clindamycin and ciprofloxacin.</p><p><strong>Results: </strong>We identified a two gene operon, herein designated <i>trexAB</i>, significantly associated with reduced susceptibility to tetracycline. The proteins encoded by the operon were predicted <i>in silico</i> to constitute a heterodimeric efflux transporter. The knockout of <i>trexAB</i> led to a 16- to 32-fold reduction in minimum inhibitory concentration (MIC) for tetracycline and a 4-fold reduction in MIC for tigecycline in the investigated strains. No differences between mutants and wildtypes were observed for other antibiotics included in the test panel. Whole genome alignment of mutants and their respective wildtypes revealed no differences other than the expected differences caused by the knockout.</p><p><strong>Conclusion: </strong>We have characterized a novel operon causing low-grade resistance to tetracycline in SD. The MIC distribution of <i>trexAB</i>-positive isolates is intersected by the current EUCAST susceptibility breakpoint, and our findings are relevant for future revisions and determinations of adequate breakpoints for tetracycline in <i>S. dysgalactiae</i>.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1583926"},"PeriodicalIF":4.6,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12256430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636605","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}