mSphere最新文献

{"title":"Establishing a new human pneumococcal standard reference serum, MPRSS-01.","authors":"Joseph M Antonello, Rocio D Murphy, Chitrananda Abeygunawardana, Juliana C Malinverni, Rajam Gowrisankar, Tina Green, Rebecca Greway, Jenna Schmauch, Adrienne Howlett, Cyrille J Bonhomme, Katrina M Nolan","doi":"10.1128/msphere.00404-24","DOIUrl":"10.1128/msphere.00404-24","url":null,"abstract":"<p><p>Measuring the immunogenicity of pneumococcal vaccines involves the use of immunoassays to measure serotype-specific immunoglobulin G (IgG) antibody levels post-vaccination with the current <i>Streptococcus pneumoniae</i> human reference serum standard (007sp) for anti-pneumococcal capsule antibodies. Development of new pneumococcal conjugate vaccines (PCVs) with additional serotypes not in 007sp (e.g., V116, a 21-valent PCV) requires a new reference serum. Antibody concentrations to 33 pneumococcal serotypes were assigned in a new Merck Pneumococcal Reference Serum Standard (MPRSS-01; Merck Pneumococcal Reference Serum Standard) using the pneumococcal electrochemiluminescence assay. MPRSS-01 was generated by pooling high-titer serum samples from adults immunized with either 23-valent pneumococcal polysaccharide vaccine (PPSV23) or V116. For the 24 serotypes with established IgG concentrations, the corresponding antibody concentrations in MPRSS-01 were assigned via direct calibration to 007sp, while a cross-standardization approach was used for the nine novel serotypes. Serotype 7F was initially chosen as the reference calibrator for cross-standardization due to parallelism across dilution-response curves demonstrated across all 33 serotypes, and an evaluation of the single-calibrator approach was conducted for the 24 serotypes. Potential systematic bias from using a unique serotype for calibration was identified and addressed by further adjusting the estimated IgG concentrations of the nine novel serotypes. Using the final MPRSS-01 antibody concentration assignments, and the calibration factor relating MPRSS-01 to 007sp, antibody concentration assignments for 007sp were provided for the nine novel serotypes. This proposal was accepted by the Center for Biologics Evaluation and Research (CBER), enabling V116 to bridge old and new human pneumococcal reference sera.IMPORTANCEImmunogenicity of pneumococcal vaccines is measured using post-vaccination serotype-specific immunoglobulin G (IgG) antibodies in serum using enzyme-linked immunoassays with the 007sp reference serum containing serotype-specific IgG for 24 pneumococcal serotypes. With the development of next-generation PCVs, a new <i>S. pneumoniae</i> reference serum standard was needed to include serotypes beyond the existing 24 in 007sp. In this study, antibody concentrations to 33 pneumococcal serotypes were assigned in a new Merck Pneumococcal Reference Serum Standard (MPRSS-01) using the pneumococcal electrochemiluminescence assay, enabling V116 to maintain the link to the historical human pneumococcal standard reference serum while utilizing the new human pneumococcal reference serum.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0040424"},"PeriodicalIF":3.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952310","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":"PWWP domain-containing protein Crf4-3 specifically modulates fungal azole susceptibility by regulating sterol C-14 demethylase ERG11.","authors":"Pengju Yu, Shuting Ye, Mi Zhou, Long Zhang, Zhongchi Zhang, Xianyun Sun, Shaojie Li, Chengcheng Hu","doi":"10.1128/msphere.00703-24","DOIUrl":"10.1128/msphere.00703-24","url":null,"abstract":"<p><p>The widespread use of azole antifungals in agriculture and clinical settings has led to serious drug resistance. Overexpression of the azole drug target 14α-demethylase ERG11 (CYP51) is the most common fungal resistance mechanism. However, the presence of additional regulatory proteins in the transcriptional response of <i>erg11</i> is not yet fully elucidated. In this study, leveraging the identified key promoter region of <i>erg11</i> that controls its response to azoles in <i>Neurospora crassa</i>, we pinpointed a protein, Crf4-3, which harbors a PWWP domain and exerts a positive regulatory influence on azole resistance, as determined by DNA pulldown assays. The removal of Crf4-3 results in heightened sensitivity to azoles while remaining unaffected by other stressors tested. Additionally, the deletion leads to the abolition of transcriptional responses of genes such as <i>erg11</i> and <i>erg6</i> to ketoconazole. Interestingly, the basal expression of <i>erg1</i>, <i>erg11</i>, <i>erg25</i>, and <i>erg3A</i> is also affected by the deletion of <i>crf4-3</i>, indicating its role in sterol homeostasis. Crf4-3 homologs are broadly distributed across the <i>Pezizomycotina</i> fungi. The gene deletion for its homologous protein in <i>Aspergillus fumigatus</i> also significantly improves sensitivity to azoles such as voriconazole, primarily through the attenuation of the transcriptional response of <i>erg11</i>. Our data, for the first time, identified Crf4-3 as a novel regulatory protein in the azole stress response of filamentous fungi, offering fresh insights into the mechanisms of azole resistance.IMPORTANCETranscriptional control of pivotal genes, such as <i>erg11</i>, stands as the primary driver of azole resistance. Although considerable effort has been dedicated to identifying transcription factors involved, our knowledge regarding the use of transcriptional regulation strategies to combat azole resistance is currently limited. In this study, we reveal that a PWWP domain-containing protein Crf4-3, which is conserved in <i>Pezizomycotina</i> fungi, modulates fungal azole sensitivity by transcriptionally regulating sterol biosynthetic genes, including <i>erg11</i>. These results also broaden the understanding of fungal PWWP domain-containing proteins regarding their roles in regulating resistance against azole antifungals. Considering research on small molecules targeting the PWWP domain in humans, Crf4-3 homolog emerges as a promising target for designing fungal-specific drugs to combat azole resistance.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0070324"},"PeriodicalIF":3.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818798","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":"Optimizing <i>in vitro</i> spherulation cues in the fungal pathogen <i>Coccidioides</i>.","authors":"Christina M Homer, Elena Ochoa, Mark Voorhies, Anita Sil","doi":"10.1128/msphere.00679-24","DOIUrl":"10.1128/msphere.00679-24","url":null,"abstract":"<p><p><i>Coccidioides</i> spp. are part of a group of thermally dimorphic fungal pathogens, which grow as filamentous cells (hyphae) in the soil and transform to a different morphology upon inhalation into the host. The <i>Coccidioides</i> host form, the spherule, is unique and highly undercharacterized due to both technical and biocontainment challenges. Each spherule arises from an environmental spore (arthroconidium), matures, and develops hundreds of internal endospores, which are released from the spherule upon rupture. Each endospore can then go on to form another spherule in a cycle called spherulation. One of the foremost technical challenges has been reliably growing spherules in culture without the formation of contaminating hyphae and consistently inducing endospore release from spherules. Here, we present optimization of <i>in vitro</i> spherule growth and endospore release, by closely controlling starting cell density in the culture, using freshly harvested arthroconidia, and decreasing the concentration of multiple salts in spherulation media. We developed a minimal medium to test spherule growth on various carbon and nitrogen sources. We defined a critical role for the dispersant Tamol in both early spherule formation and prevention of the accumulation of a visible film around spherules. Finally, we examined how the conditions under which arthroconidia are generated influence their transcriptome and subsequent development into spherules, demonstrating that this is an important variable to control when designing spherulation experiments. Together, our data reveal multiple strategies to optimize <i>in vitro</i> spherulation growth, enabling characterization of this virulence-relevant morphology.IMPORTANCE<i>Coccidioides</i> spp. are thermally dimorphic fungal pathogens found in the Southwest United States, Mexico, Central America, and South America. <i>Coccidioides</i> can infect both immunocompetent and immunocompromised people and can cause a devastating disseminated infection, including meningitis, with 30% mortality despite all currently available treatments. In this work, we tackle one of the current largest technical barriers to studying the fungus <i>Coccidioides</i>: reliably growing its host form <i>in vitro</i>. Our work is impactful because we have created a set of foundational tools for the burgeoning field of <i>Coccidioides</i> pathogenesis research. We have carefully optimized conditions that allow the development of <i>Coccidioides in vitro</i> into its pathogenic form. This work will open up many lines of investigation into the molecules that underlie <i>Coccidioides</i> pathogenesis.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0067924"},"PeriodicalIF":3.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142837933","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":"mRNA-LNP vaccines combined with tPA signal sequence elicit strong protective immunity against <i>Klebsiella pneumoniae</i>.","authors":"Ting Huang, Siyou Che, Zheng Lv, Danrui Hao, Runyu Wang, Qinxuan Yi, Ling Mei, Yang Yuan, Hang Zou, Yidong Guo, Xinrong Wang, Yiwen Chu, Kelei Zhao","doi":"10.1128/msphere.00775-24","DOIUrl":"10.1128/msphere.00775-24","url":null,"abstract":"<p><p><i>Klebsiella pneumoniae</i> is a prominent Gram-negative and encapsulated opportunistic pathogen that causes a multitude of infections such as severe respiratory and healthcare-associated infections. Despite the widespread anti-microbial resistance and the high mortality rate, currently, no clinically vaccine is approved for battling <i>K. pneumoniae</i>. To date, messenger RNA (mRNA) vaccine is one of the most advancing technologies and are extensively investigated for viral infection, while infrequently applied for prevention of bacterial infections. In the present study, we aim to construct a new mRNA vaccine encoding YidR or combining with a tissue plasminogen activator signal sequence for preventing <i>K. pneumoniae</i> infection. Adaptive immunity was determined in mRNA vaccines-immunized mice and the protective effects of mRNA vaccines were evaluated in <i>K. pneumoniae</i> infected models. The results showed that lipid nanoparticle (LNP)-YidR-mRNA vaccine was produced with good morphology, high the encapsulation efficiency, and the specific antigen was highly expressed in cells <i>in vitro</i>. In addition, immunization with either LNP-YidR or LNP-YidR-SP elicited a Th1-biased immune response, reduced bacterial load, and provided broad protection in the lung infection models. Importantly, the LNP-YidR-SP mRNA vaccine induced strong adaptive humoral and cellular immunity and increased the survivability of mice compared to the other groups. Our findings serve as a focal point for developing a potential mRNA vaccine against <i>K. pneumoniae</i>, indicating the potential of mRNA vaccines for improving next-generation bacterial vaccine.IMPORTANCE<i>K. pneumoniae</i> is a notorious and clinical bacterium that is evolving in community-acquired and nosocomial settings. This opportunistic pathogen causes severe infectious diseases, including urinary tract infection and pneumonia, and causes a concerning global public burden. Despite efforts having been created to develop different types of <i>K. pneumoniae</i> vaccines, there is no licensed vaccine for preventing <i>K. pneumoniae</i> infection. Therefore, to develop an effective tactic is essential to combat <i>K. pneumoniae</i>-caused diseases. This study provides a novel vaccine strategy against <i>K. pneumoniae</i> and a potent platform to elicit high levels of humoral and cell-meditated immunity.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0077524"},"PeriodicalIF":3.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915383","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 thermodynamic bottleneck in the TCA cycle contributes to acetate overflow in <i>Staphylococcus aureus</i>.","authors":"Nabia Shahreen, Jongsam Ahn, Adil Alsiyabi, Niaz Bahar Chowdhury, Dhananjay Shinde, Sujata S Chaudhari, Kenneth W Bayles, Vinai C Thomas, Rajib Saha","doi":"10.1128/msphere.00883-24","DOIUrl":"10.1128/msphere.00883-24","url":null,"abstract":"<p><p>During aerobic growth, <i>S. aureus</i> relies on acetate overflow metabolism, a process where glucose is incompletely oxidized to acetate, for its bioenergetic needs. Acetate is not immediately captured as a carbon source and is excreted as waste by cells. The underlying factors governing acetate overflow in <i>S. aureus</i> have not been identified. Here, we show that acetate overflow is favored due to a thermodynamic bottleneck in the TCA cycle specifically involving the oxidation of succinate to fumarate by succinate dehydrogenase. This bottleneck reduces flux through the TCA cycle, making it more efficient for <i>S. aureus</i> to generate ATP via acetate overflow metabolism. Additionally, the protein allocation cost of maintaining ATP flux through the restricted TCA cycle is greater than that of acetate overflow metabolism. Finally, we show that the TCA cycle bottleneck provides <i>S. aureus</i> the flexibility to redirect carbon toward maintaining redox balance through lactate overflow when oxygen becomes limiting, albeit at the expense of ATP production through acetate overflow. Overall, our findings suggest that overflow metabolism offers <i>S. aureus</i> distinct bioenergetic advantages over a thermodynamically constrained TCA cycle, potentially supporting its commensal-pathogenic lifestyle.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0088324"},"PeriodicalIF":3.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915430","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":"Discovery of reproductive tissue-associated bacteria and the modes of microbiota acquisition in male honey bees (drones).","authors":"Alexis Burks, Patrick Gallagher, Kasie Raymann","doi":"10.1128/msphere.00705-24","DOIUrl":"10.1128/msphere.00705-24","url":null,"abstract":"<p><p>Honey bees are the third most economically important agricultural animal in the world due to their role as pollinators. Honey bee pollination services and all hive duties are performed by female workers, while the male drones have one job to mate and share their genetics with a virgin queen from another colony. Thus, drone fitness is directly tied to queen success and colony survival, yet they have been severely understudied compared to their female counterparts. In other insects, microbes discovered in the gut and reproductive organs have been shown to be important for reproductive success and/or overall host health. To our knowledge, the existence of microbes in drone reproductive tissues has never been investigated. Moreover, our understanding of the gut microbiota of drones is severely limited, especially when compared to honey bee workers. Here, we sampled conventional drones from healthy colonies and used 16S amplicon sequencing to identify and characterize bacteria in the reproductive organs of immature and mature drones. After identifying bacteria in drone reproductive tissues, we performed a controlled experiment in which newly emerged drones were exposed to different rearing conditions in order to determine when and how they acquire their reproductive and gut microbiota. Overall, we discovered a set of core bacteria in the reproductive and gut tissues of conventionally reared drones and revealed that social interactions are important for the proper development of the drone microbiota. Determining if these bacteria play a role in drone fecundity and health should be a goal of future research efforts.</p><p><strong>Importance: </strong>Over the last decade, annual honey bee colony loss has increased, resulting in a critical need to determine what factors contribute to honey bee and colony health. Gut microbes have been shown to play important roles in the health of the nonreproductive female honey bee workers, which make up 90% or more of a honey bee colony. However, we currently know very little about the impact of microbes on the health of male honey bees (drones), who only make up a small portion of the colony population but play a very key role in the success of future colonies by mating with virgin queens. Here, we discovered microbes within the reproductive organs of drones and illustrated that social interactions with worker bees are necessary for the proper development of the gut and reproductive tissue microbial communities in drones. Further studies are needed to determine if microbes play an important role in honey bee reproductive health and fitness.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0070524"},"PeriodicalIF":3.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854566","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":"Dose-dependent serological profiling of AdCLD-CoV19-1 vaccine in adults.","authors":"Jung Hyuk Lee, Yuna Shin, Kwang-Soo Shin, Ju Yeon Park, Mi Sun Kim, Young-Shin Park, Wuhyun Kim, Joon Young Song, Ji Yun Noh, Hee Jin Cheong, Chang-Yuil Kang, Sang Hwan Seo, Jae-Ouk Kim, Deok Ryun Kim, Nathaniel S Hwang, Jae Seung Yang, Jerome H Kim, Byoung-Shik Shim, Manki Song","doi":"10.1128/msphere.00998-24","DOIUrl":"10.1128/msphere.00998-24","url":null,"abstract":"<p><p>AdCLD-CoV19-1, a chimeric adenovirus-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine, was previously reported to elicit robust antibody responses in mice and non-human primates after a single dose. In this study, we conducted a systems serology analysis to investigate changes in humoral immune responses induced by varying doses of the AdCLD-CoV19-1 vaccine in a phase I clinical trial. Serum samples from participants receiving either a low or a high dose of the vaccine were analyzed for antibody features against prototype SARS-CoV-2 spike (S) domains (full-length S, S1, S2, and receptor binding domain), as well as Fc receptor binding and effector functions. While both low- and high-dose vaccines induced robust humoral immune responses following vaccination, the quality of antibody features differed between the dose groups. Notably, while no significant difference was observed between the groups in the induction of most S1-specific antibody features, the high-dose group exhibited higher levels of antibodies and a stronger Fc receptor binding response specific to the S2 antigen. Moreover, univariate and multivariate analyses revealed that the high-dose vaccine induced higher levels of S2-specific antibodies binding to FcγR2A and FcγR3B, closely associated with antibody-dependent neutrophil phagocytosis (ADNP). Further analysis using the Omicron BA.2 variant demonstrated that the high-dose group maintained significantly higher levels of IgG and FcγR3B binding to the S2 antigen and exhibited a significantly higher ADNP response for the S2 antigen compared with the low-dose group. These findings underscore the importance of considering diverse humoral immune responses when evaluating vaccine efficacy and provide insights for optimizing adenovirus vector-based SARS-CoV-2 vaccine doses.IMPORTANCEOptimization of vaccine dose is crucial for eliciting effective immune responses. In addition to neutralizing antibodies, non-neutralizing antibodies that mediate Fc-dependent effector functions play a key role in protection against various infectious diseases, including coronavirus disease 2019. Using a systems serology approach, we demonstrated significant dose-dependent differences in the humoral immune responses induced by the AdCLD-CoV19-1 chimeric adenovirus-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine, particularly against the SARS-CoV-2 spike 2 domain. These findings highlight the importance of assessing not only neutralizing antibody titers but also the quality and functionality of antibody responses when evaluating vaccine efficacy.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0099824"},"PeriodicalIF":3.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895428","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":"Geographically widespread and novel hemotropic mycoplasmas and bartonellae in Mexican free-tailed bats and sympatric North American bat species.","authors":"Daniel J Becker, Kristin E Dyer, Lauren R Lock, Beckett L Olbrys, Shawn A Pladas, Anushka A Sukhadia, Bret Demory, Juliana Maria Nunes Batista, Micaela Pineda, Nancy B Simmons, Amanda M Adams, Winifred F Frick, M Teague O'Mara, Dmitriy V Volokhov","doi":"10.1128/msphere.00116-24","DOIUrl":"10.1128/msphere.00116-24","url":null,"abstract":"<p><p>Bacterial pathogens remain poorly characterized in bats, especially in North America. We describe novel (and in some cases panmictic) hemoplasmas (10.1% positivity) and bartonellae (25.6% positivity) across three colonies of Mexican free-tailed bats (<i>Tadarida brasiliensis</i>), a partially migratory species that can seasonally travel hundreds of kilometers. Molecular analyses identified three novel <i>Candidatus</i> hemoplasma species most similar to another novel <i>Candidatus</i> species in Neotropical molossid bats. We also detected novel hemoplasmas in sympatric cave myotis (<i>Myotis velifer</i>) and pallid bats (<i>Antrozous pallidus</i>), with sequences in the latter 96.5% related to <i>Candidatus</i> Mycoplasma haematohominis. We identified nine <i>Bartonella</i> genogroups, including those in cave myotis with 96.1% similarity to <i>Candidatus</i> Bartonella mayotimonensis. We also detected <i>Bartonella rochalimae</i> in migratory Mexican free-tailed bats, representing the first report of this human pathogen in the Chiroptera. Monthly sampling of migratory Mexican free-tailed bats during their North American occupancy period also revealed significant seasonality in infection for both bacterial pathogens, with prevalence increasing following spring migration, peaking in the maternity season, and declining into fall migration. The substantial diversity and seasonality of hemoplasmas and bartonellae observed here suggest that additional longitudinal, genomic, and immunological studies in bats are warranted to inform One Health approaches.</p><p><strong>Importance: </strong>Bats have been intensively sampled for viruses but remain mostly understudied for bacterial pathogens. However, bacterial pathogens can have significant impacts on both human health and bat morbidity and even mortality. Hemoplasmas and bartonellae are facultative intracellular bacteria of special interest in bats, given their high prevalence and substantial genetic diversity. Surveys have also supported plausible zoonotic transmission of these bacteria from bats to humans, including <i>Candidatus</i> Mycoplasma haematohominis and <i>Candidatus</i> Bartonella mayotimonensis. Greater characterization of these bacteria across global bat diversity (over 1,480 species) is therefore warranted to inform infection risks for both bats and humans, although little surveillance has thus far been conducted in North American bats. We here describe novel (and in some cases panmictic) hemoplasmas and bartonellae across three colonies of Mexican free-tailed bats and sympatric bat species. We find high genetic diversity and seasonality of these pathogens, including lineages closely related to human pathogens, such as <i>Bartonella rochalimae</i>.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0011624"},"PeriodicalIF":3.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807029","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":"Human adenovirus species B knob proteins as immunogens for inducing cross-neutralizing antibody responses.","authors":"Zhenwei Liu, Yuting Xian, Jixian Lan, Zhichao Zhou, Xiao Li, Rong Zhou, Dehui Chen, Xingui Tian","doi":"10.1128/msphere.00644-24","DOIUrl":"10.1128/msphere.00644-24","url":null,"abstract":"<p><p>The re-emerging human adenovirus (HAdV) types 3, 7, 14, and 55 of species B have caused severe or even fatal acute respiratory disease. Therefore, the development of multivalent vaccines against HAdV types 3, 7, 14, and 55 remains an important goal. In our previous study, we identified a cross-neutralizing epitope that induced broadly reactive monoclonal neutralizing antibodies against the knob proteins of HAdV types 7, 11, 14, and 55. To study the immunogenicity of HAdV species B knob proteins, we evaluated humoral immune responses to the knob proteins <i>in vivo</i> and <i>in vitro</i>. We found that the knob proteins elicited robust binding and neutralizing antibody responses after three immunizations of mice. In addition, mouse antisera raised against the knob proteins exhibited cross-neutralizing activity against original species B members. Furthermore, immunization with a mix of HAdV-3, 7, and 55 knob proteins protected Chinese tree shrews against an experimental HAdV challenge. Our results provide insight into the immunogenicity of HAdV species B knob proteins.IMPORTANCEHuman adenovirus (HAdV) species B are common pathogens causing severe pneumonia in children, and there is currently no vaccine available. Because there are many HAdV species B types, developing broad-spectrum vaccines against HAdV species B is an important research goal. Our study revealed that immunization with recombinant HAdV species B knob proteins effectively elicited cross-neutralizing antibody responses against original species B members with protective immunity. This study provides a novel insight into the immunogenicity of HAdV species B knob proteins.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0064424"},"PeriodicalIF":3.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818794","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 transcriptional regulator Lrp activates the expression of genes involved in the biosynthesis of tilimycin and tilivalline enterotoxins in <i>Klebsiella oxytoca</i>.","authors":"Miguel A De la Cruz, Hilda A Valdez-Salazar, Diana Rodríguez-Valverde, Santa Mejia-Ventura, Nayely Robles-Leyva, Tania Siqueiros-Cendón, Quintín Rascón-Cruz, Nancy León-Montes, Jorge Soria-Bustos, Fernando Chimal-Cázares, Roberto Rosales-Reyes, María L Cedillo, Jorge A Yañez-Santos, J Antonio Ibarra, Javier Torres, Jorge A Girón, James G Fox, Miguel A Ares","doi":"10.1128/msphere.00780-24","DOIUrl":"10.1128/msphere.00780-24","url":null,"abstract":"<p><p>The toxigenic <i>Klebsiella oxytoca</i> strains secrete tilymicin and tilivalline enterotoxins, which cause antibiotic-associated hemorrhagic colitis. Both enterotoxins are non-ribosomal peptides synthesized by enzymes encoded in two divergent operons clustered in a pathogenicity island. The transcriptional regulator Lrp (<i><u>l</u></i>eucine-responsive <i><u>r</u></i>egulatory <i><u>p</u></i>rotein) controls the expression of several bacterial genes involved in virulence. In this work, we have uncovered novel findings that have significant implications. We determined the transcriptional expression of <i>aroX</i> and <i>npsA</i>, the first genes of each tilimycin (TM)/tilivalline (TV) biosynthetic operon in <i>K. oxytoca</i> MIT 09-7231 wild-type and its derivatives Δ<i>lrp</i> mutant and complemented strains. Our results suggest that Lrp directly activates the transcription of both <i>aroX</i> and <i>npsA</i> genes by binding to the intergenic regulatory region in a leucine-dependent manner. Furthermore, the lack of Lrp significantly diminished the cytotoxicity of <i>K. oxytoca</i> on HeLa cells due to reduced production of TM and TV. Altogether, our data present a new perspective on the role of Lrp as a regulator in cytotoxin-producing <i>K. oxytoca</i> strains and how it controls the expression of genes involved in the biosynthesis of their main virulence factors.IMPORTANCETilimycin (TM) and tilivalline (TV) are enterotoxins that are a hallmark for the cytotoxin-producing <i>Klebsiella oxytoca</i> strains, which cause antibiotic-associated hemorrhagic colitis. The biosynthesis of TM and TV is driven by enzymes encoded by the <i>aroX</i>- and NRPS-operons. In this study, we discovered that the transcriptional regulator Lrp plays a crucial role in activating the expression of the <i>aroX</i>- and NRPS-operons, thereby initiating TM and TV biosynthesis. Our results underscore a molecular mechanism by which TM and TV production by toxigenic <i>K. oxytoca</i> strains is regulated and shed further light on developing strategies to prevent the intestinal illness caused by this enteric pathogen.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0078024"},"PeriodicalIF":3.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142838126","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}