mBio最新文献

{"title":"Distinct immune properties of the N- and C-termini of the immunosuppressive domain of Ebola virus glycoprotein.","authors":"Mathieu Iampietro, Sivakumar Periasamy, Philipp A Ilinykh, Yuan Qiu, Yakun Liu, Abhinit Nagar, Bin Gong, Alexander Bukreyev","doi":"10.1128/mbio.02278-25","DOIUrl":"https://doi.org/10.1128/mbio.02278-25","url":null,"abstract":"<p><p>Ebola virus (EBOV) causes a severe human disease with high lethality. Pathogenesis of EBOV disease is characterized by a paradoxical combination of hyperinflammation and immunosuppression. EBOV has a single envelope glycoprotein (GP), which is a type I transmembrane protein with strong immunomodulatory effects. GP contains a conserved immunosuppressive domain (ISD) with a high similarity to ISDs of envelope proteins retroviruses. To investigate the effects of ISD, a set of 17 EBOV viral-like particle (VLP) constructs containing the entire EBOV nucleoprotein, VP40, and GP with single alanine or glycine substitutions in each position of ISD was generated and tested in human peripheral blood mononuclear cells (PBMCs). Wild-type VLPs induced inflammatory responses; however, when added to pre-stimulated cells, they reduced inflammation, thus exerting immunosuppressive properties. Substitution of lysine at ISD position 5 (Lys-5) increased anti-inflammatory properties by reducing proliferative responses of VLPs and also reducing nuclear factor of activated T-cells 1 (NFAT1) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation. In contrast, substitution of tryptophan at position 14 (Trp-14) increased both the pro-inflammatory and the proliferative responses and the adhesion of VLP-infected human monocytes to microvascular endothelial cells. Thus, the ISD N- and C-termini have pro- and anti-inflammatory properties, respectively, suggesting their unique implications in the EBOV pathogenesis. Furthermore, the immunomodulating effects of ISD were also mediated by shed GP, which is abundant in the medium. These data may be useful for the development of treatments for diseases caused by EBOV by targeting the ISD.IMPORTANCEOur data suggest that the ISD N-terminus plays a role in activating immune cells and pro-inflammatory response. In contrast, the C-terminus of ISD downregulates the pro-inflammatory response through the reduction of NF-kB and NFAT activities. The data also show that EBOV GP increases the adhesion of monocytes to endothelial cells, and the effect is inhibited by the ISD C-terminus. Moreover, the data demonstrate that the immunomodulating effects of ISD are mediated not only by the virus-associated GP but also by the shed GP, which is abundant in the medium. Pathogenesis of the disease caused by EBOV is characterized by hyperinflammation and some features of immunosuppression, which could in part be affected by the complex effects of the ISD. These data indicate that targeting the ISD may be considered for the development of treatments for the disease caused by EBOV.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0227825"},"PeriodicalIF":4.7,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reconsidering the <i>Toxoplasma gondii</i> interactome: opportunities beyond crosslinking mass spectrometry.","authors":"Nathkapach K Rattanapitoon, Patpicha Arunsan, Nav La, Schawanya K Rattanapitoon","doi":"10.1128/mbio.02683-25","DOIUrl":"https://doi.org/10.1128/mbio.02683-25","url":null,"abstract":"","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0268325"},"PeriodicalIF":4.7,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to Rattanapitoon et al., \"Reconsidering the <i>Toxoplasma gondii</i> interactome: opportunities beyond crosslinking mass spectrometry\".","authors":"Tadakimi Tomita, Elizabeth Weyer, Rebekah Guevara, Simone Sidoli, Jennifer T Aguilan, Louis M Weiss","doi":"10.1128/mbio.02750-25","DOIUrl":"https://doi.org/10.1128/mbio.02750-25","url":null,"abstract":"","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0275025"},"PeriodicalIF":4.7,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combinatorial effects of tryptophan derivatives serotonin and indole on virulence modulation of enteric pathogens.","authors":"Mehmet Ali Hoskan, Vanessa Sperandio","doi":"10.1128/mbio.02067-25","DOIUrl":"10.1128/mbio.02067-25","url":null,"abstract":"<p><p>There is a wealth of signals present in the human gut that mediate host-microbiota communication and intersect with the gut-brain-axis. There is differential spatial localization of the tryptophan derivatives serotonin and indole in the gut, which are important cues for enteric pathogens to find their colonization niche. Both signals are sensed by enteric pathogens such as enterohemorrhagic <i>Escherichia coli</i> (EHEC) and <i>Citrobacter rodentium</i>, a murine pathogen extensively employed as a surrogate animal model for EHEC. EHEC and <i>C. rodentium</i> virulence determinants include genes necessary for the attaching and effacing (AE) lesion formation on enterocytes, which are contained within the locus of enterocyte effacement (LEE) pathogenicity island. Both signals inhibit LEE expression <i>in vitro</i> and during mammalian infection. The roles of indole and serotonin in virulence have been initially interrogated separately. Here, we show the combinatorial effect of these signals antagonizing each other's activity on bacterial virulence <i>in vitro</i> and during murine infection. The role of both signals <i>in vivo</i> was interrogated by manipulating the serotonin levels in mice through pharmacological and genetic strategies to increase the levels of serotonin in the gut by inhibiting the serotonin reuptake transporter (SERT). Simultaneously, indole levels were altered through infection with <i>C. rodentium</i> strains that either produce or don't indole or recolonizing the microbiota with WT or Δ<i>tnaA</i> (does not produce indole) strains of <i>Bacteroides thetaiotaomicron</i>. Individually increasing the levels of serotonin and indole in the gut decreased <i>C. rodentium</i> pathogenesis. However, when both signals were elevated simultaneously, they antagonized each other's activity.IMPORTANCEPathogens sense a plethora of signals within the gut to successfully establish colonization by precise regulation of virulence gene expression within the right niche. Our study shows that it is crucial to not disregard the interaction of different signaling mechanisms to understand the complexity of virulence regulation in enteric pathogens. Even though serotonin and indole are both tryptophan derivatives with similar structures that individually decrease bacterial virulence, combinatorial sensing of these two signals cancels out each other's effect. Understanding these sensing mechanisms provides a better insight into potential therapeutic approaches against enteric infections.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0206725"},"PeriodicalIF":4.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An investigation of gene dosage reveals that increased sensitivity to D-cycloserine divergently impacts the transience of heteroresistance in <i>Escherichia coli</i>.","authors":"Katherine J Sniezek, Mark P Brynildsen","doi":"10.1128/mbio.01490-25","DOIUrl":"10.1128/mbio.01490-25","url":null,"abstract":"<p><p>Heteroresistance describes the phenomenon where seemingly isogenic bacterial populations contain subpopulations with elevated resistance compared to the susceptible majority that are often missed in routine susceptibility testing. The enhanced resistance of those subpopulations can either be maintained (stable) or quickly lost (unstable/transient) after treatment, where transient cases return susceptibility results identical to those of original cultures. Recent work has implicated increased gene dosage of resistance determinants as a major cause of unstable heteroresistance in clinical isolates. Inspired by that work, we sought to systematically evaluate how gene dosage of an antibiotic's target network components impacted heteroresistance and its stability. To accomplish that, we used <i>Escherichia coli</i> MG1655 as a model organism, and D-cycloserine (DCS), a cell-wall synthesis inhibitor that enters through a transporter (CycA) and inhibits multiple enzymes (DdlA, DdlB, DadX, and Alr), as a model antibiotic. To measure heteroresistance, we used population analysis profiling, and to quantify stability, we used a population-level model to define a heteroresistance stability index ([Formula: see text]), which quantifies the proportion of heteroresistant subpopulation <i>j</i> that maintained elevated resistance over <i>t</i> generations. We found that increased sensitivity to DCS through gene dosage variation of <i>cycA</i> and <i>ddlB</i> divergently impacted heteroresistance stability, with <i>ddlB</i> enhancing stability and <i>cycA</i> fostering transience. These findings translated to uropathogenic <i>E. coli</i> (UTI89) and suggested that increasing the number of antibiotic targets and/or points of antibiotic entry could decrease the propensity of heteroresistance to yield stable resistance. This knowledge could impact the development of new antibiotics and improve understanding of antibiotic treatment failure.</p><p><strong>Importance: </strong>Heteroresistance is a concern because heteroresistant strains escape clinical detection and facilitate treatment failure. Heteroresistant cells can produce stably resistant or transiently resistant populations, and enhanced understanding of genetic factors that influence the level of heteroresistance and its stability has the potential to improve treatment strategies. Here, we introduce the heteroresistance stability index, which is a quantitative metric of heteroresistance stability, and use it to analyze heteroresistance of <i>Escherichia coli</i> to D-cycloserine. We investigated how gene dosage of antibiotic target network components (transporter, enzymatic targets) influences heteroresistance and its stability and found diverging outcomes on stability for comparable declines in heteroresistance. Specifically, these results suggest that designing antibiotics to enter through multiple transporters or target multiple enzymes would reduce the emergence of stable resistance.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0149025"},"PeriodicalIF":4.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating genetic, antigenic, and structural diversity in the <i>Neisseria gonorrhoeae</i> outer membrane protein, PorB: implications for vaccine design.","authors":"Odile B Harrison, Margaret Bash, Fidel Ramirez-Bencomo, Angela Thistlethwaite, Rebekah Jones, Lenka Stejskal, Eduard Sanders, Ian M Feavers, Ann Jerse, Jeremy P Derrick, Christoph M Tang, Martin C J Maiden","doi":"10.1128/mbio.01309-25","DOIUrl":"10.1128/mbio.01309-25","url":null,"abstract":"<p><p>Vaccines targeting <i>Neisseria gonorrhoeae</i> are needed to reduce disease burden and help address the problem of antimicrobial resistance, with an understanding of relationships between gonococcal genetics and molecules influencing diversity, infection, and the immune response essential for developing effective vaccine formulations. Whole-genome sequence data can be used to investigate these relationships among thousands of gonococcal isolates, allowing the study of antigenic diversity on a population scale. Such analyses typically examine antigenic diversity occurring in complete protein sequences, generating mean diversity indices and phylogenetic analyses that can inform on vaccine potential; however, to detect and measure the immune responses elicited, epitope characterization within an antigen helps guide vaccine formulations, with epitopes commonly located in surface-exposed regions of a protein. Here, we analyzed the genetic diversity of the major gonococcal antigen, PorB, in WGS from 22,227 <i>N</i>. <i>gonorrhoeae</i> isolates. We characterized the diversity of all eight surface-exposed outer membrane loops, or variable regions (VRs), and generated a PorB VR subtyping scheme to facilitate the global and temporal detection of circulating PorB subtypes. These analyses identified the presence of dominant VR combinations that persisted over time, indicative of (i) epistatic interactions between VRs and (ii) positive selection. Strain-specific, anti-PorB IgG responses directed toward distinct VR subtypes were detected in sera obtained from participants vaccinated with 4CMenB. The deconstruction of PorB into each surface-exposed loop provides a powerful approach for evaluating vaccine candidates: the methods used here allow immunodominant regions to be detected, which is invaluable for further vaccine investigations.</p><p><strong>Importance: </strong>In the context of rising global gonorrhea cases, the development of vaccines becomes a priority; however, <i>N. gonorrhoeae</i> antigenic diversity and its ability to evade the immune system complicate vaccine development. This study characterizes the genetic diversity of the outer membrane protein, PorB, a key component of the outer membrane and a major gonococcal antigen. Using genomics and machine-learning techniques, this research identified dominant PorB variants that drive the immune response, proposing potential vaccine candidates and improving our understanding of the evolutionary forces maintaining genome structure and biological fitness. Understanding these processes is crucial for designing vaccines that effectively target <i>N. gonorrhoeae</i> and combat the spread of multidrug-resistant gonococci.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0130925"},"PeriodicalIF":4.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibitors of trehalose-6-phosphate synthase activity in fungal pathogens compromise thermal tolerance pathways.","authors":"Yi Miao, Vikas Yadav, William Shadrick, Jiuyu Liu, Alexander R Jenner, Connie B Nichols, Clifford Gee, Martin Schäfer, Jennifer L Tenor, John R Perfect, Richard E Lee, Richard G Brennan, Erica J Washington","doi":"10.1128/mbio.01795-25","DOIUrl":"10.1128/mbio.01795-25","url":null,"abstract":"<p><p>Infections caused by fungal pathogens such as <i>Candida</i> and <i>Cryptococcus</i> are associated with high mortality rates, partly due to limitations in the current antifungal arsenal. This highlights the need for antifungal drug targets with novel mechanisms of action. The trehalose biosynthesis pathway is a promising antifungal drug target because trehalose biosynthesis is essential for virulence in <i>Cryptococcus neoformans</i> and <i>Candida albicans</i> and is also a mediator of fungal stress responses, such as thermotolerance. To exploit its untapped antifungal potentials, we screened the St. Jude 3-point pharmacophore library to identify small molecule inhibitors of the first enzyme in the trehalose biosynthesis pathway, trehalose-6-phosphate synthase (Tps1). Structure-guided optimization of a potent hit, SJ6675, yielded a water-soluble inhibitor named 4456dh. Employing biochemical, structural, and cell-based assays, we demonstrate that 4456dh inhibits Tps1 enzymatic activity, suppresses trehalose synthesis, and exerts a fungicidal effect. Notably, the structure of Tps1 in complex with 4456 reveals that 4456 occupies the substrate binding pocket. Importantly, 4456dh renders normally thermotolerant fungal pathogens unable to survive at elevated temperatures, which is critical as we investigate the emergence of fungi from the environment due to a warming climate. Overall, this work develops the water-soluble 4456dh as an early-stage antifungal drug that has a distinct mechanism of action compared to existing clinical antifungals.IMPORTANCEThe rise of fungal infections in recent years is alarming due to an increase in the vulnerable immunocompromised population, global temperature increase, and limited antifungal treatment options. One of the major hurdles in developing new drugs is the identification of fungal-specific antifungal drug targets due to highly conserved cellular machinery between fungi and humans. Here, we describe a small molecule inhibitor, 4456dh, of the trehalose biosynthesis pathway. This pathway is present in fungi but not in humans. Trehalose plays a critical role in stress responses such as thermotolerance in fungal pathogens and is essential for their virulence. We show that treatment with 4456dh blocks the production of trehalose and renders fungal cells inviable. Thus far, 4456dh is active against two fungal pathogens of critical importance, suggesting broad-spectrum activity.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0179525"},"PeriodicalIF":4.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First-generation N-terminal domain supersite public antibodies retain activity against Omicron-derived lineages and protect mice against Omicron BA.5 challenge.","authors":"Vincent Dussupt, Jaime L Jensen, Paul V Thomas, Letzibeth Mendez-Rivera, Kerri G Lal, Michelle Zemil McCrea, Isabella Swafford, Joana Hernandez, Rajeshwer S Sankhala, Mekhala Rao, Juhi Arora, Agnes Hajduczki, Ningbo Jian, Phyllis A Rees, Indica Showell-De Leon, Gabriel Smith, Lauren Smith, Diana Wasson, Annika Schmid, I-Ting Teng, Tongqing Zhou, Peter D Kwong, Jeffrey R Currier, William W Reiley, Dominic Paquin-Proulx, Victoria R Polonis, Natalie D Collins, Nelson L Michael, M Gordon Joyce, Shelly J Krebs","doi":"10.1128/mbio.01036-25","DOIUrl":"10.1128/mbio.01036-25","url":null,"abstract":"<p><p>Monoclonal antibodies to SARS-CoV-2 can offer prophylactic and therapeutic protection against severe disease, with particular utility for immunosuppressed and vulnerable populations. With the constant emergence of new variants, understanding the neutralizing potency of monoclonal antibodies to dynamic spike protein epitopes is crucial. We show that a set of VH1-24-derived N-terminal domain (NTD)-directed antibodies, isolated from a convalescent donor early in the pandemic, displayed remarkable neutralization resilience against many Omicron SARS-CoV-2 variants, including BA.2, BA.5, and BQ.1.1. Neutralization potency to these Omicron variants is associated with slower off-rates to the spike protein. Structural characterization of the most potent NTD antibody, WRAIR-2008, revealed a conserved mode of interaction shared with other antibodies of the same multi-donor class. WRAIR-2008 protected mice from weight loss following BA.5 challenge and reduced infectious viral titers in the lungs. Our study highlights the retention of neutralization activity and protection of first-generation VH1-24-derived NTD-directed antibodies to specific Omicron variants and provides valuable insights into the shifting landscape of SARS-CoV-2 variants that are vulnerable to select monoclonal antibodies.</p><p><strong>Importance: </strong>As SARS-CoV-2 circulating variants evolve, it is important to understand the vulnerabilities of these viruses to neutralizing antibodies. Within this manuscript, we describe first-generation antibodies isolated following infection with WA-1 that retain viral neutralization to subsequent Omicron variants by targeting a site of viral vulnerability called the NTD. This work highlights the shifting landscape of SARS-CoV-2 variants and provides mechanistic insights into how antibodies from prior infections may play a role in preventing subsequent SARS-CoV-2 variant infections.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0103625"},"PeriodicalIF":4.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Sanctuary</i>: a <i>Starship</i> transposon facilitating the movement of the virulence factor ToxA in fungal wheat pathogens.","authors":"Angus Bucknell, Hannah M Wilson, Karen C Gonçalves Dos Santos, Steven Simpfendorfer, Andrew Milgate, Hugo Germain, Peter S Solomon, Adam Bentham, Megan C McDonald","doi":"10.1128/mbio.01371-25","DOIUrl":"10.1128/mbio.01371-25","url":null,"abstract":"<p><p>There is increasing evidence that mobile genetic elements can drive the emergence of pathogenic fungal species by moving virulence genes horizontally. The 14 kbp <i>ToxhAT</i> transposon was shown to move the necrotrophic effector, <i>ToxA,</i> horizontally between wheat pathogens, namely <i>Parastagonospora nodorum</i>, <i>Pyrenophora tritici-repentis</i>, and <i>Bipolaris sorokiniana</i>. All three species utilize the ToxA protein to infect wheat. Previous work found <i>ToxhAT</i> in distinct chromosomal positions in two <i>B. sorokiniana</i> isolates, indicating that the transposon remains active in this species. Here, we confirm the movement of <i>ToxhAT</i> using long-read sequencing of eight new and one previously published <i>B. sorokiniana</i> isolates. One event of independent transposition of <i>ToxhAT</i> was observed, and target site duplications of \"TA\" were identified, confirming that this is an active transposon in this species that likely falls into the <i>Tc1/Mariner</i> transposon family. We propose renaming this non-autonomous transposon to <i>ToxTA</i>. Whole genome analysis revealed that <i>ToxTA</i> is a passenger embedded in a much larger, conserved 170-196 kbp mobile genetic element. This element, termed <i>Sanctuary</i>, belongs to the newly described <i>Starship</i> transposon superfamily. This classification is based on the presence of direct repeats, empty insertion sites, a putative tyrosine recombinase gene, and other features of <i>Starship</i> transposons. We also show that <i>ToxTA</i> has been independently acquired by two different <i>Starships</i>, <i>Sanctuary</i> and <i>Horizon,</i> which share little to no sequence identity, outside of <i>ToxTA</i>. This classification makes <i>Horizon</i> and <i>Sanctuary</i> part of a growing number of <i>Starships</i> involved in the horizontal gene transfer of adaptive genetic material between fungal species.IMPORTANCEThe work presented here expands our understanding of a novel group of mobile genetic elements called <i>Starships</i> that facilitate the horizontal exchange of numerous genes between fungal pathogens. Our analysis shows that <i>Sanctuary</i> and <i>ToxTA</i> are both active transposons within the <i>Bipolaris sorokiniana</i> genome. We also show that the smaller <i>ToxTA</i> transposon has been independently acquired by two different <i>Starships</i>, namely <i>Sanctuary</i> in <i>B. sorokiniana</i> and <i>Horizon</i> in <i>Pyrenophora tritici-repentis</i> and <i>Parastagonospora nodorum</i>. Outside of <i>ToxTA,</i> these two <i>Starships</i> share no sequence identity. The acquisition of <i>ToxTA</i> by two different mobile elements in three different fungal wheat pathogens demonstrates how horizontal transposon transfer is driving the evolution of virulence in these important wheat pathogens.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0137125"},"PeriodicalIF":4.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibitory activities of monoclonal antibodies against <i>Staphylococcus aureus</i> clumping factor A.","authors":"Biswarup Banerjee, Carla Emolo, Miaomiao Shi, Abrar Abdullah Al Fardan, Tonu Pius, Muhammad Shafiul Azam, Molly McAdow, Olaf Schneewind, Dominique Missiakas","doi":"10.1128/mbio.02197-25","DOIUrl":"10.1128/mbio.02197-25","url":null,"abstract":"<p><p><i>Staphylococcus aureus</i> infection is a frequent cause of sepsis in humans, a disease associated with high mortality and without specific intervention. Clumping factor A (ClfA) displayed on the bacterial surface plays a key role in promoting <i>S. aureus</i> replication during invasive disease. Decades of research have pointed to a wide array of ligands engaged by ClfA. The sum of these interactions supports the unique ability of this pathogen to survive and replicate in the blood stream. One such ligand is fibrin. ClfA acts as the key agglutinating factor of <i>S. aureus</i> by promoting the shielding of bacteria in fibrin cables and their physical escape from phagocytes. Here, we compare a series of monoclonal antibodies elicited against the ligand binding domain of ClfA following immunization of mice. We analyze these antibodies for their ability to neutralize ClfA interactions and to promote the uptake of staphylococci in whole blood. We find that while all the antibodies promoted opsonophagocytic uptake, only those that also inhibited ClfA interactions with ligands reduced bacterial burdens in animals following blood stream challenge with <i>S. aureus</i>.IMPORTANCEAntibody-based approaches to fight bacterial pathogens have been modeled on toxin-producing or encapsulated pathogens for which correlates of protection can be reduced to measuring antibody neutralization or complement-fixing activities using tissue-cultured cells. Such approaches have failed against <i>Staphylococcus aureus</i> raising uncertainty about the value of antibodies. Here, we use a series of mouse monoclonal antibodies directed against clumping factor A, a surface protein that allows <i>S. aureus</i> to thrive in the blood stream, to query how antibodies may be exploited against a pathogen endowed with a formidable array of virulence factors.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0219725"},"PeriodicalIF":4.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}