mSphere最新文献

{"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":"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":" ","pages":"e0071524"},"PeriodicalIF":3.7,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580445/pdf/","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":"OA","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":"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":" ","pages":"e0049724"},"PeriodicalIF":3.7,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580425/pdf/","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":"OA","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":"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":" ","pages":"e0064524"},"PeriodicalIF":3.7,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580403/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Layer segmented filamentous bacteria colonize and impact gut health of broiler chickens.","authors":"Jared Meinen-Jochum, Caleb J Skow, Melha Mellata","doi":"10.1128/msphere.00492-24","DOIUrl":"10.1128/msphere.00492-24","url":null,"abstract":"<p><p>In commercial poultry farms, chicks hatch away from their progenitors from which they acquire key host-specific microbiota, like segmented filamentous bacteria (SFB) involved in gut maturation in early life. This study investigated whether providing chicken SFB to newly hatched broilers would increase their gut maturation and resistance to bacteria relevant to broiler and human health. One-day-old Ross308 broilers were orally treated with either phosphate-buffered saline (CON) or layer-derived SFB (D-SFB). On days 5, 10, 17, and 24, feces were collected to detect and enumerate SFB and <i>Enterobacteriaceae</i>. On days 8, 15, 22, and 29, birds were euthanized, intestinal samples were collected to detect and enumerate SFB through quantitative PCR (qPCR) and microscopy and expression of genes associated with gut immune function through reverse transcription-qPCR. This study showed that, despite their host specificity, layer SFB can colonize their genetically distinct relative broilers. Ileal SFB colonization was accelerated by a week with the SFB treatment and covered the proximal, medial, and distal sections of the ileum. Colonization of the ileum by SFB in early life highly activated gene expression of intestinal barrier proteins and cytokines, e.g., IL-10 and IFNγ but not IL-17. SFB treatment reduced the level of <i>Enterobacteriaceae</i> in the gut and provided superior resistance to intestinal and extraintestinal pathogens as tested <i>in vitro</i>. Overall, early gut colonization of SFB is imperative for the maturation of the gut immune system and the establishment of a homeostatic gut environment. Improving our understanding of gut immune maturation in food-producing animals is crucial for both human and animal health.IMPORTANCEIn commercial farms, newly hatched chicks may lack host-specific microbiota that help mature their gut immune system for lifelong health benefits. Here, introducing an avian segmented filamentous bacteria (SFB) to commercially sourced chickens orally at hatch accelerated SFB colonization of the ileum. Remarkably, SFB from layers were able to colonize broilers and enhance gut immune maturation, and this immunomodulation impacted the ability to increase intestinal and extraintestinal resistance to bacteria relevant to poultry and human health. With the antibiotic restrictions in animal production, strategies that will help mitigate infections are urgently needed. In summary, we developed a live prophylactic for newly hatched chicks to improve animal health and food safety. Due to the host specificity of SFB, our data highlight the importance of investigating the molecular mechanism of SFB interaction in their own host.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0049224"},"PeriodicalIF":3.7,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","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":"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":" ","pages":"e0073424"},"PeriodicalIF":3.7,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580408/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Divergence and convergence in epiphytic and endophytic phyllosphere bacterial communities of rice landraces.","authors":"Pratibha Sanjenbam, Deepa Agashe","doi":"10.1128/msphere.00765-24","DOIUrl":"10.1128/msphere.00765-24","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Phyllosphere-associated microbes can significantly alter host plant fitness, with distinct functions provided by bacteria inhabiting the epiphytic (external surface) vs endophytic niches (internal leaf tissue). Hence, it is important to understand the assembly and stability of these phyllosphere communities, especially in field conditions. Broadly, epiphytic communities should encounter more environmental fluctuations and frequent immigration, whereas endophytic microbiota should face stronger host selection. As a result, we expect greater variability in epiphytic than endophytic communities. We analyzed the structure and stability of leaf phyllosphere microbiota of four traditionally cultivated rice landraces and one commercial variety from northeast India grown in the field for 3 consecutive years, supplemented with opportunistic sampling of eight other landraces. Epiphytic and endophytic bacterial communities shared dominant core genera such as &lt;i&gt;Methylobacterium&lt;/i&gt; and &lt;i&gt;Sphingomonas&lt;/i&gt;. Consistent with an overall strong environmental effect, both communities varied more across sampling years than across host landraces. Seeds sampled from a focal landrace did not support vertical transmission of phyllosphere bacteria, suggesting that both types of communities are assembled anew each generation. Despite these points of convergence, epiphytic communities had distinct composition and significantly higher microbial load and were more rich, diverse, modular, and unstable than endophytic communities. Finally, focused sampling of one landrace across developmental stages showed that the divergence between the two types of communities arose primarily at the flowering stage. Thus, our results show both convergent and divergent patterns of community assembly and composition in distinct phyllosphere niches in rice, identifying key bacterial genera and host developmental stages that may aid agricultural interventions to increase rice yield.IMPORTANCEPhyllosphere (leaf-associated) microbes significantly impact plant fitness, making it crucial to understand how these communities are assembled and maintained. While many studies have analyzed epiphytic (surface) phyllosphere communities, we have a relatively poor understanding of endophytic communities which colonize the very distinct niche formed inside leaf tissues. We found that across several rice landraces, both communities are largely colonized by the same core genera, indicating divergence at the species level across the two leaf niches and highlighting the need to understand the mechanisms underlying this divergence. Surprisingly, both epiphytic and endophytic communities were only weakly shaped by the host landrace, with a much greater role for environmental factors that likely vary over time. Thus, microbiome-based agricultural interventions for increasing productivity could perhaps be generalized across rice varieties but would need to account for the temporal instability of the microbiot","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0076524"},"PeriodicalIF":3.7,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The unique and enigmatic spirochete symbiont of latrunculid sponges.","authors":"Samantha C Waterworth, Gabriella M Solomons, Jarmo-Charles J Kalinski, Luthando S Madonsela, Shirley Parker-Nance, Rosemary A Dorrington","doi":"10.1128/msphere.00845-24","DOIUrl":"https://doi.org/10.1128/msphere.00845-24","url":null,"abstract":"<p><p>Bacterial symbionts are critical members of many marine sponge holobionts. Some sponge-associated bacterial lineages, such as Poribacteria, sponge-associated unclassified lineage (SAUL), and Tethybacterales, appear to have broad-host ranges and associate with a diversity of sponge species, while others are more species-specific, having adapted to the niche environment of their host. Host-associated spirochete symbionts that are numerically dominant have been documented in several invertebrates including termites, starfish, and corals. However, dominant spirochete populations are rare in marine sponges, having thus far been observed only in <i>Clathrina clathrus</i> and various species within the Latrunculiidae family, where they are co-dominant alongside Tethybacterales symbionts. This study aimed to characterize these spirochetes and their potential role in the host sponge. Analysis of metagenome-assembled genomes from eight latrunculid sponges revealed that these unusual spirochetes are relatively recent symbionts and are phylogenetically distinct from other sponge-associated spirochetes. Functional comparative analysis suggests that the host sponge may have selected for these spirochetes due to their ability to produce terpenoids and/or possible structural contributions.IMPORTANCESouth African latrunculid sponges are host to co-dominant Tethybacterales and Spirochete symbionts. While the Tethybacterales are broad-host range symbionts, the spirochetes have not been reported as abundant in any other marine sponge except <i>Clathrina clathrus</i>. However, spirochetes are regularly the most dominant populations in marine corals and terrestrial invertebrates where they are predicted to serve as beneficial symbionts. Here, we interrogated eight metagenome-assembled genomes of the latrunculid-associated spirochetes and found that these symbionts are phylogenetically distinct from all invertebrate-associated spirochetes. The symbiosis between the spirochetes and their sponge host appears to have been established relatively recently.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0084524"},"PeriodicalIF":3.7,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682455","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":"Exploring the dynamic adult hard ticks-camel-pathogens interaction.","authors":"JohnMark O Makwatta, Paul N Ndegwa, Florence A Oyieke, Peter Ahuya, Daniel K Masiga, Merid N Getahun","doi":"10.1128/msphere.00405-24","DOIUrl":"10.1128/msphere.00405-24","url":null,"abstract":"<p><p>The ability of ticks to interact and adapt to different ecologies and hosts determines their vectorial competence for various pathogens; however, ticks-livestock-pathogens interaction studies are limited. With our ticks-hosts-pathogens interface studies, we found 14 species of hard ticks feeding on various livestock. Ticks showed a strong preference for one-humped camels (<i>Camelus dromedarius</i>). The camel nostril was the most preferred predilection site. The most prevalent tick species on camels was <i>Hyalomma rufipes</i>. We found two novel <i>Amblyomma gemma</i> variants which are distinct both morphologically and genetically from previously described <i>Amblyomma gemma</i>. The signature odors from camel breath and body were attractive to adult <i>H. rufipes</i>, demonstrating ticks utilize camel-derived metabolites to find their host. Our research shows that <i>H. rufipes</i> and camel hosts have unique and shared pathogens showing <i>H. rufipes</i>' vector and dromedary camel's reservoir host qualities. Our study unravels the dynamic interactions between hard ticks, pathogens, and host camels that all influence the likelihood of pathogen adaptation and transmission dynamics.</p><p><strong>Importance: </strong>Ticks are obligatory hematophagous arachnids, serving as vectors for a wide array of pathogens that can be transmitted to animals and humans. The ability of ticks to acquire and transmit various pathogens depends on their attraction to quality reservoir hosts and the survival of the pathogens in ticks' gut and other tissues. However, the complex dynamics of tick-pathogen interaction and host-seeking behavior remain understudied. This investigation revealed notable variation in tick preference for domestic animals, with camel being the most preferred host. Moreover, our spatial analysis of tick attachment sites showed nostrils are the most preferred sites by various tick species. Our epidemiology data showed variation in the pathogens harbored by camel (host) and vector (<i>Hyalomma rufipes</i>), demonstrating the camel's efficiency as reservoir host and ticks' vector competence for various pathogens. With our behavioral experiment using <i>H. rufipes</i> and its preferred host's (camel) breath and body signature odors, we identified novel attractants for <i>H. rufipes</i>, thus offering new avenues for combating tick-borne diseases. Overall, our study presents novel insights into how multiple factors shape tick-host-pathogen interaction.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0040524"},"PeriodicalIF":3.7,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perspectives on the future of ecology, evolution, and biodiversity from the Council on Microbial Sciences of the American Society for Microbiology.","authors":"Denise M Akob, A Elizabeth Oates, Peter R Girguis, Brian D Badgley, Vaughn S Cooper, Rachel S Poretsky, Braden T Tierney, Elena Litchman, Rachel J Whitaker, Katrine L Whiteson, C Jessica E Metcalf","doi":"10.1128/msphere.00307-24","DOIUrl":"10.1128/msphere.00307-24","url":null,"abstract":"<p><p>The field of microbial ecology, evolution, and biodiversity (EEB) is at the leading edge of understanding how microbes shape our biosphere and influence the well-being of humankind and Earth. To that end, EEB is developing new transdisciplinary tools to analyze these ecologically critical, complex microbial communities. The American Society for Microbiology's Council on Microbial Sciences hosted a virtual retreat in 2023 to discuss the trajectory of EEB both within the Society and microbiology writ large. The retreat emphasized the interconnectedness of microbes and their outsized global influence on environmental and host health. The maximal potential impact of EEB will not be achieved without contributions from disparate fields that unite diverse technologies and data sets. In turn, this level of transdisciplinary efforts requires actively encouraging \"broad\" research, spanning inclusive global collaborations that incorporate both scientists and the public. Together, the American Society for Microbiology and EEB are poised to lead a paradigm shift that will result in a new era of collaboration, innovation, and societal relevance for microbiology.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0030724"},"PeriodicalIF":3.7,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunomodulatory activity of omadacycline <i>in vitro</i> and in a murine model of acute lung injury.","authors":"Madeline Sanders, Paul Beringer","doi":"10.1128/msphere.00671-24","DOIUrl":"10.1128/msphere.00671-24","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Cystic fibrosis (CF) is characterized by chronic airway obstruction, infection, and inflammation leading to progressive loss of lung function and eventual respiratory failure. Omadacycline, a tetracycline antibiotic, demonstrates &lt;i&gt;in vitro&lt;/i&gt; activity against key CF pathogens, substantial lung penetration, and increasing clinical evidence for the treatment of lung infections in people with CF (PwCF). Preliminary &lt;i&gt;in vitro&lt;/i&gt; data demonstrate that omadacycline exhibits anti-inflammatory activity. This study aims to determine the anti-inflammatory effects of omadacycline &lt;i&gt;in vitro&lt;/i&gt; and in a murine model of lipopolysaccharide (LPS)-induced lung neutrophilia. &lt;i&gt;In vitro&lt;/i&gt;, THP-1-derived macrophages were treated with omadacycline (20-100 µg/mL) 30 minutes prior to LPS stimulation. Pro-inflammatory cytokine (TNF-α, IL-1β/6), chemokine (CXCL-1/2), and MMP-9 levels were analyzed after 24 hours by ELISA. Omadacycline's effects on IL-8-induced human neutrophil chemotaxis were also investigated. &lt;i&gt;In vivo&lt;/i&gt;, omadacycline (2.5-30 mg/kg), comparators dexamethasone (1 mg/kg), and azithromycin (30 mg/kg) were administered 1 hour before and 6 hours after intranasal LPS challenge, respectively. Leukocyte counts and differentials in bronchoalveolar lavage fluid (BALF), inflammatory mediator levels in BALF and lung homogenates, pulmonary edema markers, and the severity of lung injury were evaluated 24 hours or 48 hours post-challenge. Treatment with omadacycline &lt;i&gt;in vitro&lt;/i&gt; resulted in significant, dose-dependent reductions in IL-6, CXCL-1, and MMP-9 expression and inhibition of IL-8-induced neutrophil chemotaxis. &lt;i&gt;In vivo&lt;/i&gt;, omadacycline yielded protective and therapeutic effects by reducing the production of proinflammatory cytokines and chemokines and neutrophil infiltration into the lungs, along with modestly improving lung injury severity. These preclinical results suggest that omadacycline may provide dual anti-bacterial and anti-inflammatory activities relevant to chronic lung infection treatment in PwCF.IMPORTANCENontuberculous mycobacteria, particularly &lt;i&gt;Mycobacterium abscessus&lt;/i&gt; complex (MABSC), are a major concern for people with cystic fibrosis (PwCF) due to their association with deteriorating lung function. A substantial barrier to effective treatment is the limited number of safe and effective antibiotics. Omadacycline offers a potential advancement in managing MABSC infections in cystic fibrosis due to its activity, effective penetration into pulmonary secretions, improved tolerability, and good oral bioavailability as shown in healthy volunteers. Our study is the first to explore omadacycline's effects in a model of sterile lung inflammation and acute lung injury. We found that omadacycline not only has potent anti-bacterial properties but also exhibits anti-inflammatory effects, reducing lung inflammation and injury in our preclinical models. These findings underscore omadacycline's potential as a dual-action the","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0067124"},"PeriodicalIF":3.7,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}