mSphere最新文献

{"title":"Development of blood-brain barrier-penetrating antibodies for neutralizing tick-borne encephalitis virus in the brain.","authors":"Mizuki Fukuta, Sayo Fukano, Naoya Maekawa, Shintaro Kobayashi, Shunsuke Okamoto, Minato Hirano, Junko Nio-Kobayashi, Hiroaki Kariwa, Shigeru Kawakami, Satoru Konnai, Kentaro Yoshii","doi":"10.1128/msphere.00184-25","DOIUrl":"https://doi.org/10.1128/msphere.00184-25","url":null,"abstract":"<p><p>Tick-borne encephalitis virus (TBEV) belongs to the genus <i>Flavivirus</i> and causes tick-borne encephalitis (TBE), a disease characterized by severe neurological symptoms with a high mortality rate. Currently, no specific antiviral treatments have been developed for TBE. The blood-brain barrier (BBB) restricts drug delivery to the central nervous system, posing a major challenge in developing effective therapies targeting TBEV in the brain. In this study, we developed recombinant anti-TBEV antibodies fused with BBB-penetrating rabies virus glycoprotein (RVG) peptides to facilitate their transport across the BBB. The fusion of RVG peptides to the C-terminus of the heavy chain of whole antibodies or single-chain variable fragment had minimal impact on their neutralizing ability against TBEV. The RVG fusion enhanced antibody binding to the surface of a human brain endothelial cell line and increased permeability in an <i>in vitro</i> BBB model. The RVG-fused antibodies exhibited a higher transport efficiency to the brain than the non-fused antibodies following peripheral injection in mice. Notably, the peripheral administration of the RVG-fused whole antibody after viral invasion into the brain significantly neutralized TBEV in the brains of infected mice. These findings suggest that RVG-fused antibodies represent a promising therapeutic strategy for treating TBE once the virus has entered the brain.</p><p><strong>Importance: </strong>Tick-borne encephalitis virus is a neuroinvasive pathogen that causes severe neurologic disease, significantly affecting patients' quality of life. No specific antiviral treatment is available for tick-borne encephalitis caused by virus multiplication in the brain. The delivery of drugs to the brain via peripheral administration is often obstructed by the blood-brain barrier. To develop targeted antiviral therapies for brain infections, we engineered recombinant antibodies capable of crossing the blood-brain barrier via brain-targeted ligands. These antibodies exhibited permeability across the blood-brain barrier in both <i>in vitro</i> and <i>in vivo</i> models and notably effectively neutralized the virus within the brain following peripheral administration. This study is the first to highlight the therapeutic potential of brain-targeted recombinant antibodies after viral entry into the brain, offering a promising pathway for the development of effective antiviral treatments for tick-borne encephalitis.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0018425"},"PeriodicalIF":3.7,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575853","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":"Tn-seq screens in <i>Candida glabrata</i> treated with echinocandins and ibrexafungerp reveal pathways of antifungal resistance and cross-resistance.","authors":"Timothy J Nickels, Kyle W Cunningham","doi":"10.1128/msphere.00270-25","DOIUrl":"https://doi.org/10.1128/msphere.00270-25","url":null,"abstract":"<p><p><i>Candida glabrata</i> (also known as <i>Nakaseomyces glabratus</i>) is the second most common cause of candidiasis, next to <i>Candida albicans,</i> and is rising in prevalence due to intrinsic and acquired mechanisms of antifungal resistance. This study utilizes transposon mutagenesis and deep sequencing (Tn-seq) to explore mechanisms of resistance to four different echinocandins (micafungin, anidulafungin, rezafungin, and caspofungin) and a non-echinocandin inhibitor (ibrexafungerp) of beta-1,3-glucan synthase (GS) in the BG2 strain background. Contrary to the other antifungals, caspofungin susceptibility exhibited high dependence on sphingolipid genes and low dependence on mitochondrial genes. Numerous deficiencies in mitochondrial genes increased fitness in micafungin, anidulafungin, rezafungin, and ibrexafungerp largely through effects on Pdr1, a stress-activated transcription factor known to promote fluconazole resistance. Several targets of Pdr1 (<i>RTA1, LAF1, LAC1, IPT1,</i> and <i>RSB1</i>) altered resistance to one or more of the GS inhibitors when overexpressed individually. Though Gal11 and other subunits of the mediator complex were necessary for the Pdr1 effects, an inhibitor of Gal11 (iKIX1) did not synergize with micafungin due to off-target antagonistic effects. Substantial variation was observed in the genetic resistance spectra for the different GS inhibitors within the BG2 strain background and comparison to the CBS138 strain background. The intra-strain variation was linked to gene deficiencies thought to alter phospholipid and ergosterol composition or asymmetry in cellular membranes. The findings generally support and extend earlier hypotheses that a lipid code governs GS inhibition and antifungal susceptibility in <i>C. glabrata</i>.IMPORTANCEEchinocandins and ibrexafungerp are important antifungals that target the same fungal enzyme. When the fungus acquires resistance to one of these antifungals, it may or may not exhibit cross-resistance to the others. This study investigates how every gene in the pathogenic yeast <i>Candida glabrata</i> contributes to resistance and cross-resistance to all five antifungals of this type. It offers new insights into how each antifungal interacts with the target enzyme and identifies the antifungals where cross-resistance is common or rare, providing guidance on the sequences and combinations that may be most effective in clinical settings.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0027025"},"PeriodicalIF":3.7,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575855","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":"Introduction of the transmissible mobile colistin resistance genes <i>mcr-3</i> and <i>mcr-9</i> to the USA via imported seafood.","authors":"Jouman W Hassan, Tongzhou Xu, Marwan Osman, Steven J Schiff, David Mann, Xiangyu Deng, Jeffrey T LeJeune, Issmat I Kassem","doi":"10.1128/msphere.00253-25","DOIUrl":"https://doi.org/10.1128/msphere.00253-25","url":null,"abstract":"<p><p>The emergence and global dissemination of the mobile colistin resistance genes (<i>mcr</i>) threaten the efficacy of colistin, a high-priority, critically important antibiotic that is used to treat complicated infections with multidrug-resistant Gram-negative bacteria in humans. The occurrence of <i>mcr</i> in the USA has been suggested to be relatively limited, particularly in bacteria associated with domestic foods and food animals. This is because colistin has neither been marketed nor approved for use in agriculture in the USA. However, <i>mcr</i>-carrying bacteria can occur on foods imported from countries where these genes might be relatively more prevalent. Yet, studies on <i>mcr</i> in vulnerable imported foods in the USA are lacking. To address this gap in knowledge, we assessed the role of imported seafood as a potential carrier of <i>mcr</i> genes to the USA. Imported seafood samples were aseptically collected from eight major retail stores across Georgia, USA. In-depth analyses revealed the occurrence of <i>mcr-9</i> in bacteria isolated from imported shrimp samples. The <i>mcr-9</i>-carrying bacteria were identified as <i>Serratia nevei</i>, a newly described species that belongs to the <i>Serratia marcescens</i> complex. The <i>mcr-9</i> in the <i>S. nevei</i> isolates was carried on IncHI2 plasmids that were transferable and conferred colistin resistance to naïve <i>Escherichia coli</i>. Further analysis identified a chromosomal <i>mcr-3.17</i> in <i>Aeromonas salmonicida</i> isolated from imported scallops. All the <i>mcr</i>-carrying isolates harbored other important antibiotic resistance genes. Taken together, our data showed that imported seafood, specifically shrimps, might be an overlooked source contributing to the introduction and spread of transmissible colistin resistance genes in the USA.</p><p><strong>Importance: </strong>Colistin, an important antibiotic, is used to treat certain bacterial infections in humans that can be severe and/or life-threatening. However, these bacteria can acquire the mobile colistin resistance (<i>mcr</i>) genes and become resistant to this antibiotic. Plasmid-borne <i>mcr</i> can jump between bacterial species, spreading in bacteria across a variety of hosts and niches. Therefore, monitoring the spread of <i>mcr</i> is critical to maintain the efficacy of colistin. In the USA, the occurrence of <i>mcr</i> in domestically produced food is thought to be limited. In this study, we showed that <i>mcr</i> can be carried into the USA by bacteria on imported seafood. A specific gene, <i>mcr-9</i>, was located on a plasmid that could be transferred to other bacteria. Therefore, imported seafood can be an overlooked source of <i>mcr</i> in the USA. It is important to monitor and assess <i>mcr</i> in imported seafood to control the proliferation of colistin resistance in the USA.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0025325"},"PeriodicalIF":3.7,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575854","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":"Comprehensive analysis of repetitive extragenic palindrome sequences identified in bacteria and archaea using a new web-based tool, RepRanger.","authors":"Oleg N Murashko, Connor Morgan-Lang, Chen-Hsin Albert Yu, Hsin-Nan Lin, Anna Chao Kaberdina, Shin-Yu Kung, Vladimir R Kaberdin, Sue Lin-Chao","doi":"10.1128/msphere.00124-25","DOIUrl":"https://doi.org/10.1128/msphere.00124-25","url":null,"abstract":"<p><p>Repetitive extragenic palindromic (REP) sequences were first discovered in the intergenic regions of <i>Escherichia coli</i> and later found in phylogenetically distinct bacterial species. However, their biological roles and sequence conservation remain unclear. Considering the growing number of microbial genome sequencing and annotation projects, along with the lack of online tools for REP identification, we developed a new web-based platform, RepRanger, to rapidly identify and annotate putative palindromic elements, including REPs. Using RepRanger, we identified >4,000 REPs in the <i>E. coli</i> MG1655 genome. Moreover, 81 (~52%) of its 157 small noncoding RNAs (sRNAs; known to regulate gene expression) contain REPs. Further analysis using RepRanger, alongside other bioinformatics tools, yielded 10 REP consensus motifs. Notably, REPs potentially involved in translational control (i.e., located within 15 nucleotides downstream of an open reading frame) primarily host motif 4, whereas REPs present in sRNAs predominantly encoded motif 9. Putative targets of REP-containing sRNAs include genes that rewire metabolic pathways in response to environmental changes, indicating that REPs likely contribute to bacterial adaptation. We also reveal that REP consensus motifs are similar across pathogenic and environmental <i>E. coli</i> strains but not commensal and laboratory ones. We employed RepRanger to search for REPs and confirm that they are present across bacteria and archaea. Furthermore, we uncovered similarities in REP sequences between bacterial and archaeal genomes. Thus, we demonstrate that RepRanger represents a versatile tool for discovering REPs in bacteria and archaea, providing new insights into their functions and sequence diversity.IMPORTANCERepetitive extragenic palindromic (REP) sequences were first discovered in <i>Escherichia coli</i>, but their biological roles, diversity, and sequence conservation remain unclear. We have developed a web-based tool, RepRanger, to identify and annotate putative palindromic elements, including REPs. Using RepRanger, we identified approximately 4,000 REPs in the <i>E. coli</i> MG1655 genome. We show that >50% of small noncoding RNAs (sRNAs) contain REPs. The predicted functions of REP-containing sRNAs indicate that REPs likely contribute to bacterial environmental adaptability. In addition, we have discovered REPs in pathogenic, environmental, and commensal <i>E. coli,</i> allowing us to assess their sequence similarity. We show that REPs are widely present in bacterial and archaeal genomes and share some sequence similarities. Our comparison of REPs in annotated genomes broadens the current understanding of REP sequence diversity, conservation, and function.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0012425"},"PeriodicalIF":3.7,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575852","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":"Household clusters of SARS-CoV-2 Omicron subvariants contemporaneously sequenced from dogs and their owners.","authors":"Francisco C Ferreira, Lisa D Auckland, Rachel E Busselman, Edward Davila, Wendy Tang, Ailam Lim, Nathan Sarbo, Hayley D Yaglom, Heather Centner, Heather L Mead, Ying Tao, Juan Castro, Yan Li, Jing Zhang, Haibin Wang, Lakshmi Malapati, Peter Cook, Adam Retchless, Suxiang Tong, Italo B Zecca, Ria R Ghai, Casey Barton Behravesh, Rebecca S B Fischer, Gabriel L Hamer, Sarah A Hamer","doi":"10.1128/msphere.00074-25","DOIUrl":"https://doi.org/10.1128/msphere.00074-25","url":null,"abstract":"<p><p>Monitoring the zoonotic potential of emerging SARS-CoV-2 variants in animals is a critical tool to protect public health. We conducted a longitudinal study in 47 households reporting people with COVID-19 in Texas from January to July 2022, during the first Omicron wave. We evaluated 105 people and 100 of their companion animals for SARS-CoV-2 infection at three sequential sampling events, starting 0-5 days after the first reported diagnosis of COVID-19 in the house. SARS-CoV-2 RNA was detected in 68% of people from 43 households; 95.5% of people had antibodies to SARS-CoV-2. Dogs were the only animal species positive by RT-qPCR (5.4%; 3/55), and their viral loads were consistently lower compared with those from household members. Additionally, infected dogs did not yield infectious virus. Clusters of Omicron BA.1.1, BA.2.3.4, and BA.5.1.1 in people, dogs, and a dog food bowl confirmed human-to-dog transmission within households, with no evidence of onward transmission from the infected dogs. Eleven dogs (<i>n</i> = 55) and two cats (<i>n</i> = 26) had neutralizing antibodies against SARS-CoV-2. Overall, infection was not associated with clinical signs in pets; only two animals that tested negative for SARS-CoV-2 were reported to be sick. Nearly one-third (30.2%) of households with active COVID-19 had pets exposed to SARS-CoV-2, similar to our pre-Omicron studies; however, the incidence of infection in cats was lower compared with pre-Omicron. These differences suggest that the zoonotic transmission dynamics in households may differ based on variants.IMPORTANCESARS-CoV-2 infects a broad diversity of mammals, with companion dogs and cats at risk of infection via close contact with infectious owners. Longitudinal studies sampling pets and their owners over time are essential to understanding within-household SARS-CoV-2 transmission dynamics. Our repeated sampling in households with people reporting COVID-19 found that 68% of the people in 43 households had active SARS-CoV-2 infection during at least one of the three sampling events. Although none of the 27 cats were positive, 3/55 dogs had active infections. Household clusters of three different Omicron subvariants were involved in these human-to-dog transmission events, and our data suggest reduced infection in pets during Omicron transmission compared with pre-Omicron waves. Protecting pets from SARS-CoV-2 infection remains important, as viral evolution can be accompanied by changes in the infectiousness of different hosts.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0007425"},"PeriodicalIF":3.7,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540967","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":"Human papillomavirus 16 mitigates <i>Sneathia vaginalis</i>-induced damage to cervical keratinocytes.","authors":"Phoebe V Bridy, Jasmine C Cruz, Jada L Covington, Taharah I Islam, Catherine E Hadley, Kayla Tran, Rachel Fry, Bradley A Sheffield, Myrna Serrano, Gregory A Buck, Jinlei Zhao, Katherine Y Tossas, Craig Meyers, Iain M Morgan, Claire D James, Kimberly K Jefferson","doi":"10.1128/msphere.00152-25","DOIUrl":"https://doi.org/10.1128/msphere.00152-25","url":null,"abstract":"<p><p><i>Sneathia vaginalis</i> is a bacterial component of the vaginal microbiome that is of clinical interest because of its association with preterm birth and other obstetric complications. It produces a cytotoxin, but little is known about the mechanism through which it kills epithelial cells or the role that cytotoxicity plays in bacterial survival. Recent microbiome studies demonstrate an association between <i>S. vaginalis</i> and human papillomavirus (HPV) within the female reproductive tract, suggesting that HPV and <i>S. vaginalis</i> could interact in some way within this shared niche. We analyzed 16S rRNA survey and HPV typing data from our Vaginal Human Microbiome Project and found, in agreement with other reports, that <i>S. vaginalis</i> was associated with HPV infection. To test the hypothesis that HPV promotes the growth of <i>S. vaginalis</i>, growth and cytotoxicity of <i>S. vaginalis</i> in co-culture with HPV16-positive and HPV-negative human cervical keratinocytes (HCK) were quantitatively assessed. Organotypic HCK rafts expressing HPV16 were more resistant to <i>S. vaginalis</i>-induced damage, as assessed by histology, and supported increased bacterial growth relative to HPV-negative HCK rafts. When <i>S. vaginalis</i> was co-cultured with HPV16-positive and HPV-negative HCK monolayers, cytotoxicity was observed in both HPV16-positive and HPV-negative cells, but HPV16-positive cells were more resistant to the toxic effects of the bacteria and supported bacterial growth for an extended period of time. In conclusion, HPV16 may protect cervical keratinocytes from the cytotoxic effects of <i>S. vaginalis</i>, preventing the eradication of colonized cells and supporting bacterial growth, and this could underlie the association between <i>S. vaginalis</i> and HPV <i>in vivo</i>.IMPORTANCE<i>Sneathia vaginalis</i> (<i>S. vaginalis</i>) is a bacterial species that lives in the human vagina and can cause complications during pregnancy if it invades the uterus. It is capable of killing cervical epithelial cells. Human papillomaviruses (HPV) are sexually transmitted viruses that can cause genital lesions and cervical cancer. Recently, multiple reports describe an association between <i>S. vaginalis</i> and HPV. This study used cultured cervical epithelial cells expressing the high-risk HPV type, HPV16, and HPV-negative cells to determine whether HPV promotes the growth of <i>S. vaginalis</i>. We found that HPV16 promotes the survival of cervical epithelial cells that are exposed to <i>S. vaginalis</i>. Survival of cervical epithelial cells may benefit the growth of <i>S. vaginalis</i>, which adhere to and feed off of these cells to survive in the female reproductive tract.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0015225"},"PeriodicalIF":3.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540968","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":"<i>mSphere</i>'s journey and future: a message from the new editor in chief.","authors":"Ira J Blader","doi":"10.1128/msphere.00337-25","DOIUrl":"https://doi.org/10.1128/msphere.00337-25","url":null,"abstract":"","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0033725"},"PeriodicalIF":3.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540966","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":"Novel lineages of bacteria with reduced genomes from the gut of farm animals.","authors":"Shahjahon Begmatov, Alexey V Beletsky, Andrey V Mardanov, Anastasia P Lukina, Liubov B Glukhova, Olga V Karnachuk, Nikolai V Ravin","doi":"10.1128/msphere.00294-25","DOIUrl":"https://doi.org/10.1128/msphere.00294-25","url":null,"abstract":"<p><p>Genome reduction and associated metabolic deficiencies have been described in various lineages of parasitic and symbiotic microorganisms that obtain essential nutrients from their partners, and in some free-living microorganisms that inhabit stable environments. The animal gut is a relatively stable ecosystem, characterized by an abundance of organic substances and a high concentration of microorganisms, which provides favorable conditions for the survival of microorganisms with reduced genomes. Metagenomic analysis of 49 samples of feces of farm animals (cows, sheep, yaks, and horses) revealed uncultured lineages of bacteria with reduced genomes (<1 Mbp): family UBA1242 (<i>Christensenellales</i>, <i>Firmicutes</i>), order Rs-D84 (<i>Alphaproteobacteria</i>), and family UBA9783 (<i>Opitutales</i>, <i>Verrucomicrobiota</i>), defined in genome-taxonomy database. Analysis of the genomes showed that these bacteria lacked pathways for the biosynthesis of amino acids, nucleotides, lipids, and many other essential metabolites. The UBA9783 genomes encoded a near-complete Embden-Meyerhof glycolytic pathway and the non-oxidative phase of the pentose phosphate pathway, while in UBA1242 and Rs-D84, these pathways are incomplete. All bacteria are limited to fermentative metabolism and lack aerobic and anaerobic respiratory pathways. All UBA9783 and some Rs-D84 genomes encoded F₀F₁-type ATP synthase and pyrophosphate-energized proton pump; they also can import and utilize peptides and some amino acids. While UBA9783 bacteria could thrive as specialized free-living organisms in the organic-rich gut environment, the UBA1242 and Rs-D84 lineages appear to have adopted the lifestyle of an obligate symbiont/parasite, obtaining metabolites from other cells.IMPORTANCEThe microbiota of the animal gastrointestinal tracts is a complex community of microorganisms which interact in a synergistic or antagonistic relationship and play key nutritional and metabolic roles. However, despite its importance, the gut microbiota of farm animals, especially its uncultured majority, remains largely unexplored. We performed a metagenomic analysis of the gut microbiome of farm animals and characterized three uncultured lineages of bacteria with reduced genomes (<1 Mbp) from the phyla <i>Firmicutes</i>, <i>Proteobacteria</i>, and <i>Verrucomicrobiota</i>. These bacteria were predicted to possess key metabolic deficiencies such as the inability to synthesize essential cell metabolites, suggesting their adaptation to the lifestyle of a symbiont/parasite, or a scavenger obtaining nutrients from the organic-rich gut environment. This study shows that genome reduction with metabolic specialization and adaptation to a partner-dependent lifestyle occurred through convergent evolution in several phylogenetically distant lineages of gut microbiota.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0029425"},"PeriodicalIF":3.7,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528957","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":"Dental biofilm serves as an ecological reservoir of acidogenic pathobionts in head and neck cancer patients with radiotherapy-related caries.","authors":"Julia S Bruno, Vitor Heidrich, Felipe C F Restini, Tatiana M M T Alves, Wanessa Miranda-Silva, Franciele H Knebel, Elisangela M Cóser, Lilian T Inoue, Paula F Asprino, Anamaria A Camargo, Eduardo R Fregnani","doi":"10.1128/msphere.00257-25","DOIUrl":"https://doi.org/10.1128/msphere.00257-25","url":null,"abstract":"<p><p>Radiotherapy-related caries (RRC) is an aggressive and debilitating oral toxicity that affects half of the patients who undergo radiotherapy for head and neck cancer. However, the etiology of RRC is not fully established, and there are no clinically validated methods for preventing it. To gain a better understanding of the risk factors and the microbiome's role in causing RRC, we compared clinicopathological characteristics, oncological treatment regimens, oral health condition, and the oral microbiota at three different oral sites of radiotherapy-treated patients with (RRC+) and without radiotherapy-related caries (RRC-). We observed no significant differences between these groups in the clinicopathological characteristics and treatment regimens. However, RRC+ patients were older and had poorer oral health conditions at the start of the radiotherapy treatment, with a lower number of teeth and a higher proportion of rehabilitated teeth. RRC+ patients had lower microbiota diversity and the dental biofilm of RRC+ patients displayed striking alterations in microbiome composition compared to RRC- patients, including enrichment of acidogenic species and altered metabolic potential, with a higher abundance of genes linked to energy-related pathways associated with the synthesis of amino acids and sugars. We also compared the microbiota of RRC+ tissue with conventional caries tissue, revealing lower bacterial diversity and enrichment of Lactobacillaceae members in RRC+. The insights into the irradiated oral microbiota enhance the understanding of RRC etiology and highlight the potential for microbial-targeted therapies in its prevention and treatment.</p><p><strong>Importance: </strong>This study focuses on a dedicated collection of diverse oral sites to comprehensively investigate microbial differences between patients who develop RRC and those who do not. RRC is a severe oral disease that profoundly impacts on the oral health and overall quality of life of cancer survivors. Leveraging shotgun metagenomics, we characterize the unique microbial variations in <i>in vivo</i> irradiated dental biofilms, unveiling novel insights into the microbial ecology of radiotherapy-treated patients. Furthermore, this research integrates extensive data on oral health and oncological profiles, providing a comprehensive understanding of the intricate relationship between oral microbial communities and the outcomes of radiotherapy-induced toxicity.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0025725"},"PeriodicalIF":3.7,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528956","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":"Oral and parenteral treatment with a third-generation cephalosporin promotes the proliferation of diverse ESBL-producing <i>Escherichia coli</i> in the chicken intestinal tract.","authors":"Lázaro López, Melany Jumbo, Pamela Mosquera, Gustavo Donoso, Jay Graham, Gabriel Trueba","doi":"10.1128/msphere.00227-25","DOIUrl":"https://doi.org/10.1128/msphere.00227-25","url":null,"abstract":"<p><p>The global rise of antimicrobial resistance is a major public health threat, with <i>Escherichia coli</i> facilitating the spread of extended-spectrum beta-lactamase (ESBL) genes like <i>bla</i>_CTX-M, which confer resistance to third-generation cephalosporins (3GCs). This study examines the impact of 3GC treatment on resistant <i>E. coli</i> clones and horizontal gene transfer (HGT) of ESBL genes in broiler chickens in Quito, Ecuador. Fifteen-day-old Ross broilers were divided into three groups: oral ceftriaxone (100 mg/kg), parenteral ceftriaxone (100 mg/kg intramuscular), and control (no treatment). The study included three phases: baseline, antimicrobial administration (5 days), and recovery (15 days). Fecal cultures on McConkey agar, with and without ceftriaxone (2 µg/mL), measured the ratio of 3GC-resistant lactose fermenters. Regardless of the administration route, ceftriaxone significantly increased resistant coliforms (>80%). Five <i>E. coli</i> colonies per animal and time point were analyzed using single-gene typing, with clonal candidates subjected to whole-genome sequencing. Clonal analysis revealed high genetic diversity, averaging three distinct clones per animal. A unique lineage (H34) emerged exclusively during treatment, and new clones appeared post-treatment. The <i>bla</i>_CTX-M-55 variant was the most abundant ESBL gene, persisting despite fluctuations in other <i>bla</i>_CTX-M variants. Comparative plasmid analysis suggested <i>bla</i>_CTX-M-55 HGT, as plasmids were identified in two genetically distinct <i>E. coli</i> isolates from the same host. Most plasmids belonged to IncFII, with IncX1 and IncN also present. These findings highlight how 3GC treatments rapidly impact ESBL-producing <i>E. coli</i> diversity in the intestine.IMPORTANCEThe global rise of antimicrobial resistance (AMR) poses a critical public health challenge, with <i>Escherichia coli</i> playing a central role in the spread of extended-spectrum beta-lactamase (ESBL) genes like <i>bla</i>_CTX-M, which confer resistance to third-generation cephalosporins (3GCs). This study highlights the significant impact of 3GC treatment on the frequency and diversity of 3GC-resistant <i>E. coli</i> clones and horizontal gene transfer of ESBL genes in the intestinal microbiota of broiler chickens. Understanding how antimicrobial treatments drive resistance dynamics in animal populations is crucial for developing strategies to mitigate AMR in both human and veterinary settings.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0022725"},"PeriodicalIF":3.7,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507079","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}