mSphere最新文献

{"title":"New inhibitors of the <i>Pseudomonas aeruginosa</i> enzyme, PqsE, and methods assessing their potential to induce a conformational change via active site binding.","authors":"Samantha B Orr, Hannah A Jones, Margaret G O'Hara, Kaitlyn R Smith, Isabelle R Taylor","doi":"10.1128/msphere.00826-25","DOIUrl":"https://doi.org/10.1128/msphere.00826-25","url":null,"abstract":"<p><p><i>Pseudomonas aeruginosa</i> is an opportunistic pathogen known for its ability to produce virulence factors and biofilms. These, among many other traits, enable <i>P. aeruginosa</i> to cause infections and resist treatment with antimicrobial agents. Both the ability to form biofilms and produce virulence factors are regulated via the bacterial cell-cell communication process called quorum sensing. A key molecular event that enables quorum sensing in <i>P. aeruginosa</i> is the physical interaction between an enzyme, PqsE, and a quorum-sensing receptor/transcription factor RhlR, which regulates the expression of a wide variety of virulence-associated genes. Previous work identified active site mutations in PqsE that induce a conformational change, weakening the interaction with RhlR. These mutations weakened the PqsE-RhlR interaction to the extent that the mutant strains of <i>P. aeruginosa</i> failed to colonize the lungs of a mouse. We designed a series of molecules to probe binding in the active site of PqsE as a strategy for inhibiting the PqsE-RhlR interaction. HJ1 and HJ5 are new molecules that both bind in the active site of PqsE. While HJ5 appears to bind in an alternate mode compared to HJ1, neither induces a conformational change to weaken the PqsE-RhlR interaction. Here, we introduce multiple experimental approaches to assess the way in which these new molecules engage in the PqsE active site. HJ5 can serve as a promising starting point for the development of molecules that target the PqsE active site and allosterically inhibit the interaction with RhlR, thus decreasing virulence in <i>P. aeruginosa</i>.</p><p><strong>Importance: </strong><i>Pseudomonas aeruginosa</i> is an opportunistic human pathogen that causes infections in the most vulnerable, immunocompromised patient population. Additionally, <i>P. aeruginosa</i> infections are notoriously hard to treat with even the strongest antibiotics available in the clinic. <i>P. aeruginosa</i> relies heavily on its communication mechanism, quorum sensing, in order to stage infections. The quorum sensing system presents an ideal opportunity for the discovery of new antibiotics that are effective in treating <i>P. aeruginosa</i> infections. The work here presents new tools for the development of antibiotics targeting a key protein-protein interaction of the <i>P. aeruginosa</i> quorum-sensing system. The molecules, methods, and insights described here will be of great value in the discovery of anti-quorum-sensing therapies against a pathogen that presents a formidable threat to human health.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0082625"},"PeriodicalIF":3.1,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147723317","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":"Role of the transcription factor Wor2 in biofilm formation of <i>Candidozyma auris</i>.","authors":"Marine Louvet, Jizhou Li, Maialen Areitio, Danielle Brandalise, Daniel Bachmann, Alix T Coste, Salomé LeibundGut-Landmann, Dominique Sanglard, Frederic Lamoth","doi":"10.1128/msphere.00057-26","DOIUrl":"https://doi.org/10.1128/msphere.00057-26","url":null,"abstract":"<p><p>The yeast pathogen <i>Candidozyma</i> (<i>Candida</i>) <i>auris</i> can form biofilms, which contribute to its virulence and nosocomial transmission. In this study, we identified the transcription factor Wor2 as a negative regulator of biofilm formation in <i>C. auris</i>. Wor2 hyperactivation in a strain of clade IV via the use of a protein tagging strategy resulted in downregulation of two important adhesins, <i>SCF1</i> and <i>ALS4112</i>, and decreased biofilm-forming capacity. We showed that the impact on biofilm was predominantly mediated via decreased <i>SCF1</i> expression in this strain. However, results of adhesion assays on inert surfaces and human keratinocytes found relatively modest roles of Wor2 and Scf1 in this process, suggesting that their effect on biofilm formation is complex and not limited to the adhesion step. Finally, analyses of other strains from different clades identified three distinct <i>WOR2</i> genotypes, with variable <i>WOR2</i> expression levels and distinct impacts of <i>WOR2</i> deletion on biofilm formation. Notably, Wor2 negatively regulated biofilm in strains of clades I, III, and IV with distinct profiles of <i>SCF1</i>/<i>ALS4112</i> expression, while it had no impact on biofilm in a clade II strain. Taken together, this study showed that Wor2 exhibited some distinct genotypic evolution in <i>C. auris</i> resulting in clade- or strain-specific regulatory roles and pathways in biofilm formation.IMPORTANCE<i>Candidozyma</i> (<i>Candida</i>) <i>auris</i> is a pathogenic yeast exhibiting a particular capacity for interhuman transmission via medical instruments, which was the cause of nosocomial outbreaks of candidemia. Adhesion to inert surfaces and subsequent biofilm formation is therefore important for <i>C. auris</i> propagation. This work highlights the role of the transcription factor Wor2 as a negative regulator of biofilm formation in <i>C. auris</i>. In a strain of clade IV, Wor2 was shown to downregulate two important adhesins (<i>SCF1</i> and <i>ALS4112</i>). Interestingly, Wor2 exhibited different genotypes across <i>C. auris</i> clades and strains, which were associated with distinct differential expression of <i>WOR2</i>, <i>ALS4112</i>, and <i>SCF1</i>, and possibly distinct roles in biofilm formation.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0005726"},"PeriodicalIF":3.1,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147723336","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":"Bacterial alteration of redox stressors impacts environmental stability of influenza A virus.","authors":"Matthew R Williams, Hannah M Rowe","doi":"10.1128/msphere.00125-26","DOIUrl":"https://doi.org/10.1128/msphere.00125-26","url":null,"abstract":"<p><p>Influenza A virus (IAV) causes annual morbidity and mortality and remains a constant pandemic threat due to the emergence of novel strains. Therefore, understanding the factors important in host-to-host transmission of IAV is a key control point for protecting individual and public health. Transmission is highly heterogeneous with viral factors and host inflammatory and immune factors being implicated. Also implicated is the upper respiratory microbiome. While typically thought to act indirectly on viral pathogenesis, in an immunomodulatory capacity to enhance or reduce susceptibility to viral infection, recent studies on the pathogenesis of IAV have identified direct interactions between the virus and upper respiratory pathobiont bacteria. We hypothesize that the bacterial cells and their metabolites co-shed into respiratory droplets with IAV particles alter the viability of the IAV particles in the environment, therefore altering the capacity for host-to-host transmission. In this investigation, we utilize a simplified model of fomite transmission in the absence of confounding host factors and demonstrate how oxidative stress from both the environment and the metabolic activity of <i>Streptococcus pneumoniae</i> contributes to the killing of IAV, while catalase or the metabolic activity of <i>Staphylococcus aureus</i> can protect IAV from environmental or pneumococcally produced reactive oxygen species. These findings support a mechanism for bacterial modulation of viral transmission where bacterial metabolic products present in the respiratory droplet are capable of stabilizing and destabilizing viral particles during environmental transit and therefore modulating viral transmissibility.IMPORTANCEInfluenza A virus is a major cause of illness and death every year. A key knowledge gap exists in understanding what factors modulate viral transmission. One potential mediator of viral transmission is the bacteria that are found in the human nasopharynx. However, the mechanisms responsible for bacterial modulation of viral transmission are unclear. Here, we utilize a simplified model of environmental survival where we expose viral particles to indoor environmental conditions in the presence of bacterial cells. We demonstrate that hydrogen peroxide produced by <i>Streptococcus pneumoniae</i> reduces viral environmental survival, while incubation with catalase or viable <i>Staphylococcus aureus</i> cells can protect viral particles from <i>S. pneumoniae</i>-mediated viability loss. This supports a model of trans-kingdom bacterial-viral interactions where bacterial metabolites produced in the respiratory droplet are capable of modulating viral environmental survival and therefore transmission.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0012526"},"PeriodicalIF":3.1,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147723279","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":"Persistence of azole-resistant <i>Aspergillus fumigatus</i> in a southeastern United States environmental hotspot: a prospective genomic study.","authors":"Brandi N Celia-Sanchez, Amanda R Santos, Jorge Chavez, Brian Schwem, Bruno C Rediguieri, Elizabeth Misas, Lindsay Parnell, Shawn R Lockhart, Anastasia P Litvintseva","doi":"10.1128/msphere.00016-26","DOIUrl":"https://doi.org/10.1128/msphere.00016-26","url":null,"abstract":"<p><p><i>Aspergillus fumigatus</i> is a globally distributed fungal pathogen that can infect humans and is commonly found in the environment. Azole antifungals are the primary treatment for <i>A. fumigatus</i> infections; however, the emergence of azole resistance has become an important public health issue. This resistance is often linked to the use of agricultural fungicides and is primarily caused by tandem repeats (TRs) in the <i>cyp51A</i> promoter, along with mutations in the coding region, leading to pan-azole resistance. Azole-resistant <i>A. fumigatus</i> has been identified in patients across the United States and has been found in environmental soil samples from 38 states. A previous study conducted in the southeastern United States detected azole-resistant <i>A. fumigatus</i> in the environment. To further investigate the persistence of these resistant strains, soil samples were collected over three time periods. Whole genome sequencing was performed on isolates from each sampling date, and results were compared to publicly available isolates using phylogenetic, principal component, and ADMIXTURE analyses. These findings demonstrated that the same strains of TR-based azole-resistant <i>A. fumigatus</i> persisted in the same environmental hotspot over time. Additionally, we observed high levels of recombination between different clades, which may contribute to the ongoing presence of <i>A. fumigatus</i> in the United States. These findings highlight the environmental persistence of azole-resistant strains and underscore the need for monitoring antifungal resistance in environmental settings to better understand its potential clinical implications.IMPORTANCE<i>Aspergillus fumigatus</i> is a fungal pathogen that poses a substantial threat to humans, particularly in high-risk populations, with mortality rates reaching 90%. It is also a saprophyte that is commonly found in agricultural settings. Azoles are the primary antifungal treatment for <i>A. fumigatus</i> infections; however, azole-resistant strains have emerged, particularly in Europe and Asia, over the past two decades. Recently, such strains have also been isolated from clinical cases in the United States and identified in environmental soil samples from 38 states. In this study, azole-resistant <i>A. fumigatus</i> was isolated with three different variants of tandem repeat mutations in the <i>cyp51A</i> promoter region from southeastern U.S. soil samples collected over three time periods. These findings demonstrate that resistant strains can persist in the environment for at least 12 months, suggesting that established environmental hotspots can serve as ongoing reservoirs for resistant strains.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0001626"},"PeriodicalIF":3.1,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147723310","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":"Targeted metatranscriptomic detection of viruses from floors for simultaneous evaluation of respiratory disease burden and viral variant identification.","authors":"Amanda C Carroll, Aaron Hinz, Alexandra M A Hicks, Engluy Khov, Tamara Van Bakel, Evgueni Doukhanine, Michael Fralick, Caroline Nott, Rees Kassen, Nisha Thampi, Laura A Hug, Derek MacFadden, Alex Wong","doi":"10.1128/msphere.00086-26","DOIUrl":"https://doi.org/10.1128/msphere.00086-26","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Built environment surveillance is a proven approach for tracking disease burden of some viruses within hospitals and long-term care facilities. However, studies in clinical settings are lacking for simultaneously surveying targets in a built environment using targeted metatranscriptomics. We swabbed six discrete floor locations within an acute care center's emergency department (ED) in Ottawa, Canada, and sequenced cDNA using a 132 viral taxa panel, identifying viral burden across sampling locations and time. The determined SARS-CoV-2 variant profile across time was matched to provincial variant prevalence. The correlation between metatranscriptomic read abundances and reported cases of influenza A, SARS-CoV-2, and RSV was assessed. We quantified these via qPCR and assessed the correlation of Cq versus metatranscriptomic reads for these viruses. We sequenced a median of 1,302,882 reads per sample from 38 floor swabs collected during peak respiratory viral season (November 2022-February 2023). Diversity of viral communities varied significantly across locations in the ED. SARS-CoV-2 variant abundance shifts matched the changing infection landscape concurrently reported in Ontario. Relationships between targeted metatranscriptomic read ratios and clinical burden were not statistically significant, although we found modest correspondence between qPCR signal and read depth for RSV and SARS-CoV-2. This approach characterized the viral communities and the within-species diversity within an ED. Correlating sequencing-derived data with disease burden for three key respiratory viruses was inconsistent, with the exception of significant correlation between metatranscriptomic reads and Cq data for SARS-CoV-2. We were able to recover the distribution of clinically reported SARS-CoV-2 variants from the floor swab data.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;Environmental surveillance is useful for estimating the disease burden for certain viruses. qPCR is commonly used for surveillance of wastewater and built environments, including during the COVID-19 pandemic, but single, multiplexed reaction targets are limited. Targeted metagenomic or metatranscriptomic approaches can accurately quantify microbial populations of interest in an environment, reduce off-target sequencing, and evaluate a broader number of targets than qPCR assays. Here, we assessed the capacity of a targeted viral metatranscriptomic panel to correlate viral abundance in the hospital built environment with key pathogens of interest, including influenza A, RSV, and SARS-CoV-2. Our results suggest that targeted metatranscriptomics may identify viral communities in healthcare facilities, including strain-level detection capability. However, this approach must be validated for its effectiveness in viral surveillance that accurately reflects disease burden. This work contributes to a growing toolkit for pathogen surveillance, a critical endeavor to safeguard against outbreaks of known and emergin","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0008626"},"PeriodicalIF":3.1,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147723313","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":"Liquid-infused silicone catheters reduce fungal burden and inflammation in <i>Candidozyma auris</i> bladder infections.","authors":"Alyssa Ann La Bella, Hope Akegbe, Caitlin Howell, Felipe H Santiago-Tirado, Ana Lidia Flores-Mireles","doi":"10.1128/msphere.00098-26","DOIUrl":"10.1128/msphere.00098-26","url":null,"abstract":"<p><p><i>Candidozyma auris</i> is a high-priority, emerging fungal pathogen frequently isolated from urine in healthcare settings. These isolates are often associated with indwelling urinary catheters, a primary risk factor for catheter-associated urinary tract infections (CAUTIs). Despite its clinical prevalence, the mechanisms of <i>C. auris</i> colonization and pathogenesis within the bladder remain poorly understood. In this study, we screened <i>C. auris</i> isolates from diverse clades using an <i>in vitro</i> biofilm model and <i>in vivo</i> murine models of uncomplicated UTI and CAUTI. While <i>in vitro</i> biofilm formation varied among isolates, the presence of a catheter <i>in vivo</i> significantly enhanced fungal burden in the bladder. Notably, one strain (B11103) caused rapid systemic dissemination and mortality. To address this, we evaluated a liquid-infused silicone (LIS) catheter coating, which has previously shown efficacy against other uropathogens. The LIS coating significantly reduced <i>C. auris</i> attachment <i>in vitro</i> and, crucially, mitigated fungal burden on both the catheter and bladder tissue <i>in vivo</i> across all tested strains. For the hypervirulent B11103 strain, LIS catheters also significantly reduced dissemination to the kidneys and bloodstream. Furthermore, cytokine analysis revealed that <i>C. auris</i> CAUTI upregulates IL-6, CSF3, and CXCL1; importantly, this damaging inflammatory response was also dampened by the LIS catheter. These findings demonstrate that catheterization potentiates <i>C. auris</i> pathogenicity and identify LIS catheters as a promising, antimicrobial-sparing strategy to prevent colonization, systemic spread, and inflammation during <i>C. auris</i> CAUTI.IMPORTANCEThis research addresses the critical public health challenge posed by the emergence of <i>Candidozyma auris,</i> elucidating its pathogenesis in the urinary tract, the second-most common yet understudied reservoir. Here, we find that <i>C. auris</i> exhibits plasticity in its ability to form biofilms in urine and cause uncomplicated urinary tract infections (UTIs) and catheter-associated UTIs (CAUTIs). Importantly, we show that our liquid-infused silicone (LIS) catheters effectively disrupt this cycle by reducing fungal burden, preventing systemic spread, and dampening the damaging host inflammatory response. This work establishes the urinary tract as a critical niche for systemic entry and provides a validated strategy for infection prevention. Urinary catheters make <i>C. auris</i> dangerous, but this liquid-infused silicone coating is fighting back.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0009826"},"PeriodicalIF":3.1,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147691117","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":"TgJosephin and TgRad23 are important for anti-IFN-γ virulence via deubiquitination of SPM1 in <i>Toxoplasma</i>.","authors":"Emi Hashizaki, Yuta Tachibana, Junpei Fukumoto, Eizo Takashima, Hidetaka Kosako, Daisuke Okuzaki, Miwa Sasai, Masahiro Yamamoto","doi":"10.1128/msphere.00137-26","DOIUrl":"https://doi.org/10.1128/msphere.00137-26","url":null,"abstract":"<p><p><i>Toxoplasma gondii</i>, which can virtually infect all warm-blooded cells, secretes various virulence factors to evade interferon-gamma (IFN-γ)-dependent host immunity. While these secreted proteins are widely characterized, the molecular mechanisms important for virulence within the parasite are unclear. In this study, we aimed to investigate the roles of non-secretory proteins of <i>T. gondii</i> in immunosuppression. Deletion of deubiquitinase TgJosephin resulted in attenuated virulence in wild-type mice but not in mice lacking the interferon-gamma receptor (IFNγR). Moreover, TgJosephin expression was maintained by TgRad23, a protein involved in DNA repair and protein shuttling. Notably, TgJosephin depletion increased ubiquitination of subpellicular microtubule protein 1 (SPM1), a stabilizing component of the parasite microtubules, and mutating its ubiquitination sites restored virulence in the absence of TgJosephin. We propose TgJosephin as a novel virulence factor maintained by TgRad23 and a virulence pathway involving SPM1 metabolism.IMPORTANCE<i>Toxoplasma gondii</i> is an obligate parasite whose infection can be detrimental when combined with pregnancy or immunodeficiency. Studies on <i>T. gondii</i> virulence have revealed various secretory proteins that inhibit the host interferon-gamma (IFN-γ) immune response. However, much of the broader virulence landscape remains unclear. To explore the unknown molecular pathways of <i>T. gondii</i> virulence in mice, we searched for immunosuppressive functions in genes encoding non-secretory proteins, associated with fundamental cellular processes of the virulent type I strain. Here, we found that TgJosephin, a highly conserved deubiquitinase, was important for virulence in wild-type mice but not mice lacking the IFN-γ receptor (IFNγR). In addition, TgJosephin expression was dependent on TgRad23, and loss of TgJosephin led to increased ubiquitination of a microtubule protein SPM1. Our results suggest a novel anti-IFN-γ pathway of <i>T. gondii</i> mediated by TgJosephin and SPM1 deubiquitination.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0013726"},"PeriodicalIF":3.1,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147674562","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":"Fungal endophytes of cactus (<i>Stenocereus</i> spp.) as a potential alternative to alleviate drought stress in juveniles of <i>Theobroma cacao</i> L. ICS95.","authors":"Karen Sofía Trujillo-Ortigoza, Angelis Marbello-Santrich, Juliana González-Tobón, Fermín Rada, Marcela Guevara-Suarez, Silvia Restrepo","doi":"10.1128/msphere.00865-25","DOIUrl":"https://doi.org/10.1128/msphere.00865-25","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;i&gt;Theobroma cacao&lt;/i&gt;, one of Colombia's most socially significant crops, faces productivity challenges due to drought. This stress can reduce growth, leaf area, and stomatal conductance (&lt;i&gt;K&lt;/i&gt;&lt;sub&gt;&lt;i&gt;s&lt;/i&gt;&lt;/sub&gt;) and generate reactive oxygen species. Therefore, exploring solutions to enhance drought tolerance is crucial. This study aimed to (i) design a strategy to select fungal root endophytes with the potential to alleviate drought stress in plants; (ii) isolate fungi from &lt;i&gt;Stenocereus&lt;/i&gt; spp. to induce drought tolerance in &lt;i&gt;T. cacao&lt;/i&gt; genotype ICS95. &lt;i&gt;In vitro&lt;/i&gt; drought tolerance screening identified five fungal isolates that exhibited the highest biomass production and less than 20% biomass loss under drought conditions compared with non-drought conditions. The soil of juvenile &lt;i&gt;T. cacao&lt;/i&gt; plants was inoculated with these isolates, and physiological and morphological parameters were assessed, including leaf water potential (Ψ&lt;sub&gt;L&lt;/sub&gt;), &lt;i&gt;K&lt;/i&gt;&lt;sub&gt;&lt;i&gt;s&lt;/i&gt;&lt;/sub&gt;, proline content, and growth. The results showed a significant decrease in Ψ&lt;sub&gt;L&lt;/sub&gt; and &lt;i&gt;K&lt;/i&gt;&lt;sub&gt;&lt;i&gt;s&lt;/i&gt;&lt;/sub&gt; in juveniles under drought stress, which was observed across all five fungal isolates tested. However, juveniles inoculated with &lt;i&gt;Phoma&lt;/i&gt; sp. exhibited significantly less negative Ψ&lt;sub&gt;L&lt;/sub&gt; than non-inoculated controls, suggesting that this fungus may be a potential inducer of drought tolerance in &lt;i&gt;T. cacao&lt;/i&gt; ICS95. One intriguing result was that plants inoculated with this fungus accumulated less proline during the drought treatment. Under non-drought conditions, juveniles inoculated with &lt;i&gt;Fusarium&lt;/i&gt; sp. exhibited a significant increase in specific leaf area under non-drought conditions compared to non-inoculated control. These findings suggest that fungal endophytes associated with &lt;i&gt;Stenocereus&lt;/i&gt; spp. affect the physiological response of cacao juveniles under drought conditions.IMPORTANCE&lt;i&gt;Theobroma cacao&lt;/i&gt; is among the world's most valuable crops, yet its productivity is increasingly threatened by fluctuating rainfall and prolonged drought. Identifying sustainable strategies to mitigate these impacts is therefore critical. Xerophilic plants, such as &lt;i&gt;Stenocereus&lt;/i&gt; spp., harbor diverse fungal endophytes adapted to arid environments, representing a promising source of microorganisms capable of enhancing stress tolerance in commercial crops. Our study demonstrates that cactus-derived endophytes could improve drought resilience in juveniles of cacao, in particular, the fungal endophyte &lt;i&gt;Phoma&lt;/i&gt; sp. maintained less negative leaf water potential values under drought stress conditions and exhibited significantly lower proline accumulation compared to non-inoculated controls. Furthermore, under favorable conditions, some endophytes could promote growth by increasing leaf area compared to non-inoculated plants. These findings underscore the potential of fungal endophytes from arid ecosystems as biotechnological","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0086525"},"PeriodicalIF":3.1,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147675343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The missing thread of One Health efforts: improper drug disposal as an overlooked driver of antimicrobial resistance.","authors":"Sandip Mukhopadhyay, Falguni Debnath, Debjit Chakraborty","doi":"10.1128/msphere.00586-25","DOIUrl":"https://doi.org/10.1128/msphere.00586-25","url":null,"abstract":"<p><p>With gradual recognition of the components and the stakeholders, \"One Health approach\" became a global strategy for mitigating antimicrobial resistance (AMR). However, the role of improper pharmaceutical disposal, particularly antimicrobials at the household level, remains largely overlooked within One Health strategies. Expired and unused medicines are frequently discarded into household waste, drains, or open environments. The bioactive pharmaceutical residues enter soil, surface water, groundwater, and sediments. Conventional waste management and wastewater treatment systems are not designed to remove these compounds, resulting in chronic, low-level environmental exposure. Such sub-inhibitory concentrations of antimicrobials exert sustained selective pressure on environmental microbial communities, which promotes the emergence, persistence, and dissemination of resistant bacteria. Discarded antimicrobials persist in aquatic and terrestrial ecosystems, reshape microbial communities, disrupt nutrient cycling, and accelerate horizontal gene transfer. The environmental resistome, a vast genetic reservoir connecting environmental microbes with human and animal pathogens, plays a key role in resistance amplification. Evidence from India and other low and middle-income countries reveals the widespread presence of \"clinically important resistance genes,\" including extended-spectrum β-lactamases and carbapenemases, in non-clinical environments. Residues and resistant bacteria can bioaccumulate in aquatic organisms and livestock, facilitating transmission through food chains and communities and often beyond routine surveillance. Despite its significance, household pharmaceutical waste management is largely absent from national and global AMR action plans. Incorporating safe drug disposal may serve as the missing thread in the One Health, apart from environmental monitoring and ecopharmacovigilance, which are critical to reduce environmental selection pressure and resistance propagation.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0058625"},"PeriodicalIF":3.1,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147674863","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 machine learning-based approach to identify viral biomarkers of human respiratory emissions from oral and nasal metagenomes.","authors":"Kathryn Langenfeld, Peter Arts, Abigail Monahan, Allyson Criswell, Krista R Wigginton, Melissa B Duhaime","doi":"10.1128/msphere.00113-26","DOIUrl":"https://doi.org/10.1128/msphere.00113-26","url":null,"abstract":"<p><p>Humans spend approximately 90% of their lives in built environments, making virus transmission indoors a key determinant of health. Environmental sampling of respiratory viral pathogens is often challenging because of frequent non-detect measurements. Non-detect measurements do not differentiate between samples containing low or no pathogens from samples that simply lack respiratory expulsions altogether. This ambiguity can be resolved by scanning samples for a biomarker of human respiratory emissions. To do so, reliable biomarkers for environmental monitoring need to be identified. Ideal biomarkers are prevalent across individuals, abundant, and unique to the human respiratory tract. Here, we present a new machine learning-based approach to query for suitable biomarker candidates from publicly available metagenomes and apply it to identify viral biomarkers of healthy oral and nasal microbiomes. Twelve viral biomarker candidates were selected from 1,232 curated viral operational taxonomic units. The viral biomarker candidates had as much as 63% prevalence across respiratory metagenomes, and prevalence was further increased to 77%-81% by combining two or three biomarkers. Real-time PCR confirmed that these viral biomarkers were prevalent and abundant in nasal swabs and saliva samples. Notably, top candidate biomarkers remained stable and detectable through multiple lab purification steps, increasing confidence in their viral origins and demonstrating their suitability for environmental monitoring. These findings demonstrate that existing metagenomes can be used to identify effective biomarker candidates for environmental sampling.IMPORTANCEDeveloping non-pharmaceutical interventions to reduce virus transmission indoors relies on robust environmental monitoring methods. Monitoring viral pathogens is challenging because of frequent non-detect measurements that introduce uncertainty. For instance, a non-detect measurement could indicate either the absence of the pathogen or simply the lack of human respiratory activity and, thus, exposure. To aid in distinguishing these scenarios, this study identifies viruses from the human respiratory tract using publicly available sequencing data that can be incorporated into environmental monitoring as biomarkers of human respiratory activity. These viral biomarkers will improve indoor monitoring to help enact interventions to mitigate virus transmission. Furthermore, our approach to identify biomarkers from existing metagenomes can be adapted for future biomarker identification in any system.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0011326"},"PeriodicalIF":3.1,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147675286","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}