mSphere最新文献

{"title":"Erratum for Choi et al., \"Human saliva modifies growth, biofilm architecture, and competitive behaviors of oral streptococci\".","authors":"Allen Choi, Kevin Dong, Emily Williams, Lindsey Pia, Jordan Batagower, Paige Bending, Iris Shin, Daniel I Peters, Justin R Kaspar","doi":"10.1128/msphere.00868-24","DOIUrl":"https://doi.org/10.1128/msphere.00868-24","url":null,"abstract":"","PeriodicalId":19052,"journal":{"name":"mSphere","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583895","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":"Pneumococcal extracellular vesicles mediate horizontal gene transfer via the transformation machinery.","authors":"Sarah Werner Lass, Bailey E Smith, Shaw Camphire, Rory A Eutsey, Jojo A Prentice, Saigopalakrishna S Yerneni, Ashni Arun, Andrew A Bridges, Jason W Rosch, James F Conway, Phil Campbell, N Luisa Hiller","doi":"10.1128/msphere.00727-24","DOIUrl":"https://doi.org/10.1128/msphere.00727-24","url":null,"abstract":"<p><p>Bacterial cells secrete extracellular vesicles (EVs), the function of which is a matter of intense investigation. Here, we show that the EVs secreted by the human pathogen <i>Streptococcus pneumoniae</i> (pneumococcus) are associated with bacterial DNA on their surface and can deliver this DNA to the transformation machinery of competent cells. These findings suggest that EVs contribute to gene transfer in Gram-positive bacteria and, in doing so, may promote the spread of drug resistance genes in the population.IMPORTANCEThis work extends our understanding of horizontal gene transfer and the roles of extracellular vesicles in pneumococcus. This bacterium serves as the model for transformation, a process by which bacteria can take up naked DNA from the environment. Here, we show that extracellular vesicles secreted by the pneumococcus have DNA on their surface and that this DNA can be imported by the transformation machinery, facilitating gene transfer. Understanding EV-mediated gene transfer may provide new avenues to manage the spread of antibiotic drug resistance.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583918","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":"mSphere of Influence: Venturing outside the biology canon with sex and gender.","authors":"Victoria Prieto-Echagüe","doi":"10.1128/msphere.00594-24","DOIUrl":"https://doi.org/10.1128/msphere.00594-24","url":null,"abstract":"<p><p>Victoria Prieto-Echagüe works in the field of signaling by primary cilia, adipogenesis, and obesity. In this mShpere of Influence article, she reflects on how gender studies, feminism, and societal movements such as #metoo may inform all areas of biomedical and health research. She describes how they inspired her to incorporate sex as a biological variable (SABV) principle to her research exploring sex-specific mechanisms in obesity and metabolic diseases and argues that incorporating SABV is crucial for advancing precision medicine and addressing healthcare inequities.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583901","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 promiscuous biotin ligase TurboID reveals the proxisome of the T3SS chaperone IpgC in <i>Shigella flexneri</i>.","authors":"Nathaline Haidar-Ahmad, Kyle Tomaro, Mathieu Lavallée-Adam, François-Xavier Campbell-Valois","doi":"10.1128/msphere.00553-24","DOIUrl":"10.1128/msphere.00553-24","url":null,"abstract":"<p><p>Promiscuous biotin ligases derived from the bacterial enzyme BirA are used to identify proteins vicinal to a bait protein, thereby defining its proxisome. Despite the popularity of this approach, surprisingly little is known about its use in prokaryotes. Here, we compared the activity of four widely used promiscuous biotin ligases in the cytoplasm of <i>Shigella flexneri</i>, a pathogenic subgroup of <i>Escherichia coli</i>. Our data indicate that the kinetics of TurboID's biotinylating activity is the highest of those tested. In addition, TurboID showed reduced interaction with the natural BirA binding partners, BccP and the biotin operator, when compared to its ancestor BioID. We therefore evaluated the ability of TurboID to probe the proxisome of the type III secretion system (T3SS) chaperone IpgC and the transcriptional activator MxiE. When the T3SS is inactive (off-state), these proteins are inhibited by forming complexes with the T3SS substrates OspD1 and IpaBC, respectively. In contrast, when the T3SS is active (on-state), OspD1 and IpaBC are secreted allowing MxiE and IpgC to interact together and activate their target genes. The results obtained with the IpgC and TurboID fusions capture a good fraction of these known interactions. It also suggests that the availability of IpgC increases in the on-state, resulting in a greater number of proteins detected in its vicinity. Among these is the T3SS ATPase SpaL (also known as Spa47 or SctN), further supporting the notion that chaperones escort their substrate to the T3SS. Interestingly, a specific subset of proteins conserved in <i>E. coli</i> completes the IpgC proxisome in the on-state.IMPORTANCEPromiscuous biotin ligases are widely used to study protein function in eukaryotes. Strikingly, their use in prokaryotes has been rare. Indeed, the small volume and the cytoplasmic location of the biotin ligase's natural binding partners in these organisms pose unique challenges that can interfere with the study of the proxisome of proteins of interest. Here, we evaluated four of the most common promiscuous biotin ligases and found TurboID was best suited for use in the cytoplasm of <i>Shigella flexneri</i>. Using this method, we extended the proxisome of IpgC beyond its known direct binding partners involved in the regulation of the type III secretion system (T3SS) signaling cascade. Of particular interest for further study are transcription factors and housekeeping proteins that are enriched around IpgC when the T3SS is active. We propose a model in which the increased availability of IpgC in the on-state may allow cross-talk of the T3SS with other cellular processes.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546510","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":"Adaptation to zinc restriction in <i>Streptococcus agalactiae</i>: role of the ribosomal protein and zinc-importers regulated by AdcR.","authors":"M Melet, S Blanchet, P Barbarin, E A Maunders, S L Neville, V Rong, L Mereghetti, C A McDevitt, A Hiron","doi":"10.1128/msphere.00614-24","DOIUrl":"10.1128/msphere.00614-24","url":null,"abstract":"<p><p>Zinc (Zn) is an essential cofactor for numerous bacterial proteins and altering Zn availability is an important component of host innate immunity. During infection, adaptation to both Zn deprivation and excess is critical for pathogenic bacteria development. To understand the adaptive responses to Zn availability of <i>Streptococcus agalactiae</i>, a pathogen causing invasive infections of neonates, global transcriptional profiling was conducted. Results highlight that in response to Zn limitation, genes belonging to the AdcR regulon, the master regulator of Zn homeostasis in streptococci, were overexpressed. Through a combination of <i>in silico</i> analysis and experimental validation, new AdcR-regulated targets were identified. Among them, we identified a duplicated ribosomal protein, RpsNb, and an ABC transporter, and examined the role of these genes in bacterial growth under Zn-restricted conditions. Our results indicated that, during Zn restriction, both the RpsNb protein and a potential secondary Zn transporter are important for <i>S. agalactiae</i> adaptation to Zn deficiency.</p><p><strong>Importance: </strong><i>Streptococcus agalactiae</i> is a bacterial human pathobiont causing invasive diseases in neonates. Upon infection, <i>S. agalactiae</i> is presented with Zn limitation and excess but the genetic systems that allow bacterial adaptation to these conditions remain largely undefined. A comprehensive analysis of <i>S. agalactiae</i> global transcriptional response to Zn availability shows that this pathogen manages Zn limitation mainly through upregulation of the AdcR regulon. We demonstrate that several AdcR-regulated genes are important for bacterial growth during Zn deficiency, including human biological fluids. Taken together, these findings reveal new mechanisms of <i>S. agalactiae</i> adaptation under conditions of metal deprivation.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546501","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":"Analytical measuring interval, linearity, and precision of serology assays for detection of SARS-CoV-2 antibodies according to CLSI guidelines.","authors":"Katarzyna Haynesworth, Troy J Kemp, Sarah A Loftus, Jordan Metz, Nicholas C Castro, Jimmie Bullock, David Fetterer, Ligia A Pinto","doi":"10.1128/msphere.00393-24","DOIUrl":"10.1128/msphere.00393-24","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Serology testing is commonly used to evaluate the immunogenicity of COVID-19 vaccines and measure antibodies as a marker of previous infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study, four laboratory-developed serology enzyme-linked immunosorbent assays (SARS-CoV-2 anti-Spike and anti-Nucleocapsid immunoglobin G [IgG] and immunoglobin M [IgM]) calibrated to the WHO International Standard 20/136 were validated via analytical measuring interval (limit of blank [LOB], limit of detection [LOD], and limit of quantification [LOQ]), linearity, and precision according to the Clinical and Laboratory Standards Institute (CLSI) guidelines EP17-A2, EP06 2nd Edition, and EP05-A3. For Spike IgG, LOB was 3.0 binding antibody units per milliliter (BAU/mL), LOD was 4.1 BAU/mL, and LOQ was 27.1 BAU/mL. For Nucleocapsid IgG, LOB was 1.9 BAU/mL, LOD was 3.2 BAU/mL, and LOQ was 24.6 BAU/mL. For Spike IgM, LOB was 57.1 BAU/mL, LOD was 69.0 BAU/mL, and LOQ was 113.5 BAU/mL. For Nucleocapsid IgM, LOD was 242.2 BAU/mL, LOD was 289.9 BAU/mL, and LOQ was 572.4 BAU/mL. Each assay displayed good linearity (max % deviation from linearity (≥LOQ) = 10.7%). The result of within-run repeatability evaluation for medium positive samples was 7.7% for Spike IgG, 4.6% for Nucleocapsid IgG, 7.5% for Spike IgM, and 10.1% for Nucleocapsid IgM. The total precision, including medium positive sample variability across 20 days, three reagent kits, and two operators, was 13.5% for Spike IgG, 14.5% for Nucleocapsid IgG, 17.6% for Spike IgM, and 16.2% for Nucleocapsid IgM. The assays were successfully validated following the applicable CLSI guidelines. All assays met the ±20% deviation from linearity and the ±20% coefficient of variation specification for precision and repeatability.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;Reliable and validated serology assays are of increasing importance as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus continues to evolve and cause outbreaks. Validation of serology assays along with calibration to the International and National Standards (such as anti-SARS-CoV-2 Immunoglobulin WHO International Standard 20/136 or Frederick National Laboratory for Cancer Research's National Serology Standard COVID-NS01097) is critical to ensuring that results from clinical studies are reliable and comparable among various assays and laboratories. We describe the design and execution of a comprehensive study that established the analytical measuring intervals, linearity, precision, and repeatability of four in-house developed serology enzyme-linked immunosorbent assays (SARS-CoV-2 anti-Spike immunoglobin G [IgG] and immunoglobin M [IgM] and anti-Nucleocapsid IgG and IgM) following applicable Clinical and Laboratory Standards Institute (CLSI) guidelines. Overall, this study provides practical guidance on experimental design strategies and data analysis techniques, pertaining to the validation of COVID-19 serology","PeriodicalId":19052,"journal":{"name":"mSphere","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546502","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>In vivo</i> RNA sequencing reveals a crucial role of Fus3-Kss1 MAPK pathway in <i>Candida glabrata</i> pathogenicity.","authors":"Xinreng Mo, Xiangtai Yu, Hao Cui, Kang Xiong, Shan Yang, Chang Su, Yang Lu","doi":"10.1128/msphere.00715-24","DOIUrl":"https://doi.org/10.1128/msphere.00715-24","url":null,"abstract":"<p><p><i>Candida glabrata</i> is an important and increasingly common pathogen of humans, particularly in immunocompromised hosts. Despite this, little is known about how this fungus causes disease. Here, we applied RNA sequencing and an <i>in vivo</i> invasive infection model to identify the attributes that allow this organism to infect hosts. Fungal transcriptomes show a dramatic increase in the expression of Fus3 and Kss1, two mitogen-activated protein kinases (MAPKs), during invasive infection. We further demonstrate that they are both highly induced under a combination of serum and high CO₂ conditions. Deletion of both <i>FUS3</i> and <i>KSS1</i>, but neither gene alone, results in a reduced fungal burden in organs, as well as in the gastrointestinal tract in the DSS (Dextran Sulfate Sodium)-induced colitis model. Similarly, the defect in persistence in macrophages and attenuated adhesion to epithelial cells are observed when <i>FUS3</i> and <i>KSS1</i> are both disrupted. The <i>fus3 kss1</i> double mutant also displays defects in the induction of virulence attributes such as genes required for iron acquisition and adhesion and in the anti-fungal drug tolerance. The putative downstream transcription factors Ste12 (1), Ste12 (2), Tec1, and Tec2 are found to be involved in the regulation of these virulence attributes. Collectively, our study indicates that an evolutionary conserved MAPK pathway, which regulates mating and filamentous growth in <i>Saccharomyces cerevisiae</i>, is critical for <i>C. glabrata</i> pathogenicity.</p><p><strong>Importance: </strong>The MAPK signaling pathway, mediated by closely related kinases Fus3 and Kss1, is crucial for controlling mating and filamentous growth in <i>Saccharomyces cerevisiae</i>, but this pathway does not significantly impact hyphal development and pathogenicity in <i>Candida albicans</i>, a commensal-pathogenic fungus of humans. Furthermore, deletion of Cpk1, the ortholog of Fus3 in pathogenic fungus <i>Cryptococcus neoformans</i>, has no effect on virulence. Here, we demonstrate that the MAPK pathway is crucial for the pathogenicity of <i>Candida glabrata</i>, a fungus that causes approximately one-third of cases of hematogenously disseminated candidiasis in the United States. This pathway regulates multiple virulence attributes including the induction of iron acquisition genes and adhesins, as well as persistence in macrophages and organs. Our work provides insights into <i>C. glabrata</i> pathogenesis and highlights an example in which regulatory rewiring of a conserved pathway confers a virulent phenotype in a pathogen.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546499","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":"A novel antibody treatment reduces deformed wing virus loads in the western honey bee (<i>Apis mellifera</i>).","authors":"N J J MacMillan, B M Hause, T Nordseth, A Felden, J W Baty, J L Pitman, P J Lester","doi":"10.1128/msphere.00497-24","DOIUrl":"https://doi.org/10.1128/msphere.00497-24","url":null,"abstract":"<p><p>The deformed wing virus (<i>Iflavirus aladeformis</i>) (DWV) is a key driver of colony loss in the western honey bee (<i>Apis mellifera</i>). Here, we demonstrate that orally delivered anti-DWV antibodies can act systemically to reduce DWV loads in naturally infected honey bees. Immunoglobulin Y (IgY) was produced in adult chickens against two DWV proteins, harvested from their eggs, and fed to bees in a sucrose solution. An enzyme-linked immunosorbent assay demonstrated that orally delivered anti-DWV IgY migrated to the hemolymph. We next assessed the ability of orally delivered anti-DWV IgY to reduce DWV viral loads in naturally infected bees using qPCR. An antibody treatment resulted in a significant eightfold viral load reduction in DWV-infected bees. Our findings demonstrate the potential for antibody treatments to help mitigate the losses attributed to DWV in <i>A. mellifera</i>.</p><p><strong>Importance: </strong>Deformed wing virus (DWV) is considered to be a key component of declining honey bee health which threatens global food production. The virus can result in significantly shortened lifespan, deformities in developing bees, and impaired cognition. There is currently no method to directly control the virus. The virus can be indirectly controlled with acaricidal treatments that target a key vector, the parasitic varroa mite (<i>Varroa destructor</i>). But acaricide resistance and a lack of effective alternatives for the control of both Varroa and DWV are major threats to beekeeping and the wider agricultural industry. Our research presents a significant development in the ability to reduce DWV burden in honey bees using IgY antibodies. Moreover, immunoglobulin Y has the potential to be more broadly established as a new treatment modality to combat other pathogens and parasites in <i>A. mellifera.</i></p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546500","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":"Detection of <i>Hepatovirus A</i> (HAV) in wastewater indicates widespread national distribution and association with socioeconomic indicators of vulnerability.","authors":"Alessandro Zulli, Elana M G Chan, Alexandria B Boehm","doi":"10.1128/msphere.00645-24","DOIUrl":"https://doi.org/10.1128/msphere.00645-24","url":null,"abstract":"<p><p>Wastewater-based epidemiology, which seeks to assess disease occurrence in communities through measurements of infectious disease biomarkers in wastewater, may represent a valuable tool for understanding the occurrence of hepatitis A infections in communities. In this study, we measured concentrations of <i>Hepatovirus A</i> (HAV) RNA, in samples from 191 wastewater treatment plants spanning 40 US states and the District of Columbia from September 2023 to June 2024 and compared the measurements with traditional measures of disease occurrence. Nationally, 13.76% of the 21,079 wastewater samples were positive for HAV RNA, and both concentrations and positivity rates were associated with NNDSS hepatitis A case data nationally (Kendall rank correlation coefficient = 0.20, concentrations; and 0.33, positivity rate; both <i>P</i> < 0.05). We further demonstrated that higher rates of wastewater HAV detection were positively associated with socioeconomic indicators of vulnerability including homelessness and drug overdose deaths (both <i>P</i> < 0.0001). Areas with above average levels of homelessness were 48% more likely to have HAV wastewater detections, while areas with above average levels of drug overdose deaths were 14% more likely to have HAV wastewater detections. Using more granular case data, we present a case study in the state of Maine that reinforces these results and suggests a potential lead time for wastewater over clinical case detection and exposure events. The ability to detect HAV RNA in wastewater before clinical cases emerge could allow public health officials to implement targeted interventions like vaccination campaigns.IMPORTANCEDespite the existence of a highly effective vaccine for hepatitis A, outbreaks in vulnerable populations remain common. The disease can be asymptomatic or subclinical, and disproportionately impacts populations with inadequate access to healthcare, leading to a severe underestimation of the occurrence of this viral infection. This study investigates the potential for wastewater measurements of biomarkers of the causative agent of hepatitis A (HAV RNA) to provide insights into disease occurrence. Results highlight the potential for wastewater-based epidemiology to be a complementary tool to traditional surveillance for monitoring and controlling HAV transmission.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546505","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":"Cell aggregation mediated by <i>ACE2</i> deletion in <i>Candida auris</i> modulates fungal colonization and host immune responses in the skin.","authors":"Abishek Balakumar, Abigail Cox, Shankar Thangamani","doi":"10.1128/msphere.00734-24","DOIUrl":"https://doi.org/10.1128/msphere.00734-24","url":null,"abstract":"<p><p><i>Candida auris</i> is an emerging multi-drug-resistant fungal pathogen that colonizes the skin and causes invasive infections in hospitalized patients. Multi-cellular aggregative phenotype is widely reported in the <i>C. auris</i> isolates, but its role in skin colonization and host immune response is not yet known. In this study, we generated aggregative phenotype by deleting the <i>ACE2</i> gene in <i>C. auris</i> and determined the fungal colonization and host immune response using an intradermal mouse model of <i>C. auris</i> skin infection. Our results indicate that mice infected with <i>ace2</i>Δ strain had significantly lower fungal load after 3 and 14 days post-infections compared to the non-aggregative wild-type and the <i>ACE2</i> reintegrated strain. The colonization of <i>ace2</i>Δ is associated with increased recruitment of CD11b⁺ Ly6G⁺ neutrophils and decreased accumulation of CD11b⁺ Ly6 C^hi inflammatory monocytes and CD11b⁺ MHCII⁺ CD64⁺ macrophages. Furthermore, Th17 cells and type 3 innate lymphoid cells (ILCs) were significantly increased in the skin tissue of <i>ace2</i>Δ infected mice. Our findings suggest that aggregative phenotype mediated by <i>ACE2</i> deletion in <i>C. auris</i> induces potent neutrophil and IL-17-mediated immune response and reduces fungal colonization in the skin.IMPORTANCE<i>C. auris</i> is a rapidly emerging fungal pathogen that can colonize hospitalized patients, especially in skin tissue, and cause invasive infections. <i>C. auris</i> isolates exhibit morphological heterogeneity, and the multicellular aggregative phenotype of <i>C. auris</i> is reported frequently in clinical settings. Understanding the role of fungal morphotypes in colonization, persistence, and immune response in the skin microenvironment will have potential applications in clinical diagnosis and novel preventive and therapeutic measures. Here, we utilized the murine model of intradermal infection and determined that the aggregative phenotype of <i>C. auris</i> as the result of <i>ACE2</i> gene deletion elicits potential innate and adaptive immune responses in mice. These observations will help explain the differences in the skin colonization and immune responses of the aggregative morphotype of <i>C. auris</i> and open the door to developing novel antifungal therapeutics.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546503","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}