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Pharmacokinetic-pharmacodynamic modeling of a highly potent and broadly neutralizing anti-CD4 trimeric nanobody to inhibit HIV-1 infection. 高效和广泛中和抗cd4三聚体纳米体抑制HIV-1感染的药代动力学-药效学建模。
IF 3.8 2区 生物学
Microbiology spectrum Pub Date : 2025-09-19 DOI: 10.1128/spectrum.00805-25
Xiaoqing Fan, Kangna Cao, Xilin Wu, Xiaoyu Yan
{"title":"Pharmacokinetic-pharmacodynamic modeling of a highly potent and broadly neutralizing anti-CD4 trimeric nanobody to inhibit HIV-1 infection.","authors":"Xiaoqing Fan, Kangna Cao, Xilin Wu, Xiaoyu Yan","doi":"10.1128/spectrum.00805-25","DOIUrl":"https://doi.org/10.1128/spectrum.00805-25","url":null,"abstract":"<p><p>Nb<sub>457</sub> is a novel anti-CD4 nanobody derived from a CD4-immunized alpaca, exhibiting high potency and broad-spectrum activity against HIV-1. This study aims to use pharmacokinetic-pharmacodynamic (PK-PD) modeling that characterizes the time-course of Nb<sub>457</sub> trimeric nanobody Nb<sub>457</sub>-Nb<sub>HSA</sub>-Nb<sub>457</sub> and viral load in mice. The serum concentrations of Nb<sub>457</sub>-Nb<sub>HSA</sub>-Nb<sub>457</sub> and HIV-1 load were modeled using a target-mediated drug disposition (TMDD) PK-PD model following intraperitoneal and subcutaneous administration of 400 µg in mice. All model parameters were estimated with high precision, with relative standard errors below 50%. The TMDD PK-PD model successfully captured the observed PK/PD profiles, demonstrating the strong therapeutic potential of Nb<sub>457</sub>-Nb<sub>HSA</sub>-Nb<sub>457</sub> for HIV-1 treatment. Furthermore, the model was extrapolated to assess the feasibility of Nb<sub>457</sub>-Nb<sub>HSA</sub>-Nb<sub>457</sub> for HIV-1 treatment in humans. The simulated viral growth trajectories at a dose of 20 mg/kg once every 2 days resulted in a downward trend in the slope of the viral trajectory, suggesting a failure to maintain replication and ultimately leading to viral suppression. Additionally, increasing the dosage or frequency of administration could further enhance the inhibition of viral replication. The simulated human PK-PD supports Nb<sub>457</sub>-Nb<sub>HSA</sub>-Nb<sub>457</sub> as a promising anti-HIV-1 agent. This mechanistic TMDD PK-PD model provides a valuable tool to support the clinical development of Nb<sub>457</sub>-Nb<sub>HSA</sub>-Nb<sub>457</sub> by enabling simulations of various dosing strategies to evaluate its efficacy and safety.</p><p><strong>Importance: </strong>HIV-1 continues to pose a global health crisis, with millions of individuals depending on lifelong antiretroviral therapy, which faces significant challenges such as drug resistance and adherence issues. Nanobodies, which are small antibody fragments, present a promising alternative due to their high specificity, stability, and ease of production. Our study introduces Nb457-NbHSA-Nb457, a novel trimeric nanobody engineered to block HIV-1 entry by binding to CD4, the primary receptor for the virus. Using advanced pharmacokinetic-pharmacodynamic modeling, we predict the behavior of this therapy in humans, effectively bridging preclinical findings to clinical application. This research not only advances a new class of HIV therapeutics but also establishes a framework to expedite the development of nanobody-based drugs for infectious diseases, offering hope for simpler and more effective treatments to combat the pandemic.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0080525"},"PeriodicalIF":3.8,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086450","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}
引用次数: 0
Rapid colorimetric antimicrobial susceptibilities direct from positive blood culture for Gram-negative bacteria. 革兰氏阴性菌阳性血培养的快速比色法抗菌药物敏感性。
IF 3.8 2区 生物学
Microbiology spectrum Pub Date : 2025-09-19 DOI: 10.1128/spectrum.02147-25
Prakash C Khanal, Joseph C Richardson, Katherine G Richardson, Gregory L Damhorst, Owen J Oertell, Alexandra Filbrun, Eileen M Burd, Robert M Dickson
{"title":"Rapid colorimetric antimicrobial susceptibilities direct from positive blood culture for Gram-negative bacteria.","authors":"Prakash C Khanal, Joseph C Richardson, Katherine G Richardson, Gregory L Damhorst, Owen J Oertell, Alexandra Filbrun, Eileen M Burd, Robert M Dickson","doi":"10.1128/spectrum.02147-25","DOIUrl":"https://doi.org/10.1128/spectrum.02147-25","url":null,"abstract":"<p><p>Bloodstream infections (BSIs) have become increasingly challenging to treat due to emerging antimicrobial resistance (AMR). As rapid administration of appropriate antimicrobials is crucial to positive patient outcomes, clinical alternatives to slow phenotypic antimicrobial susceptibility testing (AST) must be developed. We developed an automated real-time, colorimetric assay (ChroMIC) that phenotypically determines minimum inhibitory concentrations (MICs) directly from positive blood culture. Gram-negative bacteria within positive blood cultures from 83 patients were directly analyzed with ChroMIC. Both ChroMIC MICs and the much slower VITEK 2 MICs for each of seven antibiotics were compared to broth microdilution (BMD). Direct-from-blood-culture ChroMIC MICs were obtained without the ~18-hour growth and isolation steps needed to obtain both VITEK 2 and BMD MICs. ChroMIC assays yielded >90% categorical and essential agreement within 7 h from the start of the experiment and within 4 h of initial growth detection. ChroMIC minor, major, and very major errors were all comparable to, or in the case of VMEs, better than, those from VITEK 2 ASTs-the latter being performed only after an additional ~18-hour subculturing delay. As these patient blood samples were run in parallel with VITEK 2 MICs, a retrospective impact analysis on patient care suggests that ChroMIC could have facilitated faster therapeutic decision-making in nearly all cases, saving an average of >35 and >43 h for antimicrobial escalation and de-escalation, respectively, compared to VITEK 2.</p><p><strong>Importance: </strong>The often sluggish pace of phenotypic antimicrobial susceptibility testing (AST), relative to sepsis progression, limits flexibility in altering patient treatment. We report a new direct-from-blood culture phenotypic AST that delivers excellent results within ~7 h of blood culture positivity. This rapid and accurate determination of optimal bloodstream infection treatment was compared in a retrospective study on patient blood cultures that flagged positive for Gram-negative pathogens. Although standard clinical methods were used to guide treatment, our testing was performed in parallel and could have enabled correction of the treatment course ~40 h earlier than was actually performed. Once clinically implementable, such innovative, low-labor, automated, and accurate susceptibility determinations hold great potential for improving patient outcomes and lowering overall healthcare costs.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0214725"},"PeriodicalIF":3.8,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086474","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}
引用次数: 0
The effect of temperature on phytoplankton physiology: a mesocosm and modeling study. 温度对浮游植物生理的影响:一个中生态和模拟研究。
IF 3.8 2区 生物学
Microbiology spectrum Pub Date : 2025-09-18 DOI: 10.1128/spectrum.00457-25
Gabrielle Armin, Gergely Boros, Mariann Kis, Máté Burányi, Hajnalka Horváth, Krisztina Krassován, Takako Masuda, Gábor Bernát, Keisuke Inomura
{"title":"The effect of temperature on phytoplankton physiology: a mesocosm and modeling study.","authors":"Gabrielle Armin, Gergely Boros, Mariann Kis, Máté Burányi, Hajnalka Horváth, Krisztina Krassován, Takako Masuda, Gábor Bernát, Keisuke Inomura","doi":"10.1128/spectrum.00457-25","DOIUrl":"https://doi.org/10.1128/spectrum.00457-25","url":null,"abstract":"<p><p>Strategies that focus on reducing nutrient loading to freshwater lakes have historically been successful in improving water quality by curbing large phytoplankton blooms. However, as waters warm, little is known about the resultant phytoplankton physiology and ensuing perturbations in the food web that may occur. Here, we designed a mesocosm experiment to investigate the impact of warming water on phytoplankton physiology and further validate a previously developed, coarse-grained model that predicts the key aspects of phytoplankton physiology, including elemental stoichiometry and macromolecular allocation, across varying temperatures. We found that higher temperatures double the maximum cellular density (cells L<sup>-1</sup>) of phytoplankton, suggesting that high temperature stimulates cell division over maximizing carbon storage. Also, the cells in warmer waters dedicate fewer resources to proteins and RNA production, leading to higher fractions of carbon allocated to storage. This work illustrates the potential impact warming waters may have on the ecosystem, as higher fractions of carbohydrates are often associated with less nutritious food for higher trophic levels.IMPORTANCEWe take a novel approach to investigating the impact of warming on phytoplankton physiology by utilizing mesocosms and a coarse-grained cellular model. Previous work in this field tends to use idealized laboratory experiments, mesocosms, or models alone. By synthesizing model and mesocosm results, we test the model's ability to capture physiology in semi-natural environments. We conducted this experiment under phosphorus limitation and saw high cell densities in the heated, treatment tanks. Thus, warming waters may negate some successful management practices that curb eutrophication. With increased temperatures, we also observed increased N:P values in both the experimental and model results, which may be due to the combined effects of a lack of P storage, fewer enzymes required, and a corresponding decrease in RNA production. Our model predictions closely aligned to mesocosm observations, suggesting the capability of our model to represent lower trophic organisms in ecosystem models.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0045725"},"PeriodicalIF":3.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081142","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}
引用次数: 0
A rapid and accurate protocol for quantifying living Acanthamoeba castellanii cysts. 一种快速准确的定量活棘阿米巴囊的方法。
IF 3.8 2区 生物学
Microbiology spectrum Pub Date : 2025-09-18 DOI: 10.1128/spectrum.01170-25
Kazushi Matsubara, Ryohei Hirose, Norihide Hasegawa, Takumi Minamiyama, Taku Kano, Akinobu Sai, Minoru Yamada, Takaaki Nakaya
{"title":"A rapid and accurate protocol for quantifying living <i>Acanthamoeba castellanii</i> cysts.","authors":"Kazushi Matsubara, Ryohei Hirose, Norihide Hasegawa, Takumi Minamiyama, Taku Kano, Akinobu Sai, Minoru Yamada, Takaaki Nakaya","doi":"10.1128/spectrum.01170-25","DOIUrl":"https://doi.org/10.1128/spectrum.01170-25","url":null,"abstract":"<p><p>The accurate quantification of living <i>Acanthamoeba castellanii</i> (AC) cysts after various interventions is essential for evaluating the effectiveness of AC cyst disinfection and their environmental stability. The current protocol for measuring living AC cysts requires 7 days to complete, posing a substantial challenge. In this study, we aimed to develop a rapid protocol that markedly reduces the time required to accurately quantify living AC cysts. Clinical and standard strain AC cysts were inoculated into 96-well plates and incubated in peptone-yeast extract-glucose (PYG) medium with varying concentrations of fetal bovine serum (FBS) and CO<sub>2</sub> levels. Excystation was monitored under an inverted microscope, and the living AC cyst counts (LACC) were calculated. We found that the excystation of AC cysts was enhanced by increasing the FBS concentration in the PYG medium and increasing the CO<sub>2</sub> concentration during culture, which collectively significantly reduced the duration required for quantification. Specifically, by supplementing PYG medium with 5% or more FBS and incubating at 2.5% CO<sub>2</sub> or higher, measurements could be completed within only 3 days for standard and clinical AC strain cysts. Notably, this rapid protocol maintained the same accuracy as the conventional 7 day protocol and provided high accuracy in the LACC assay for samples exposed to disinfectants. In summary, the rapid protocol we developed can reduce the time required for measurement by more than half compared to current protocols and will contribute to substantially expediting the evaluation of the effectiveness of disinfectants and other drugs against AC cysts.IMPORTANCE<i>Acanthamoeba castellanii</i> (AC) is a pathogenic microbe that causes refractory <i>Acanthamoeba</i> keratitis (AK). AC cysts are highly durable and resistant to various disinfectants, making effective disinfection, which is essential for mitigating AK, difficult. Currently, it takes 7 days to determine disinfection effectiveness against AC cysts because it involves measuring viable AC cyst counts after disinfection. However, the novel, accurate method for quantifying living AC cysts developed in this study can be completed within 3 days, reducing the time required for measurement by more than half compared to conventional methods, and will markedly streamline the evaluation of disinfectant effectiveness against AC cysts. Moreover, this quantitative method can potentially be applied to shorten the time required for quantifying living cysts of other amoebas.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0117025"},"PeriodicalIF":3.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081105","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}
引用次数: 0
Activity of HOCl-generating e-bandage with clinically available hydrogels against Staphylococcus aureus and Acinetobacter baumannii biofilms. 临床可用的水凝胶生成hocl的电子绷带对金黄色葡萄球菌和鲍曼不动杆菌生物膜的活性。
IF 3.8 2区 生物学
Microbiology spectrum Pub Date : 2025-09-18 DOI: 10.1128/spectrum.01762-25
Eda Dagsuyu, Paige Kies, Melissa J Karau, Robin Patel, Haluk Beyenal
{"title":"Activity of HOCl-generating e-bandage with clinically available hydrogels against <i>Staphylococcus aureus</i> and <i>Acinetobacter baumannii</i> biofilms.","authors":"Eda Dagsuyu, Paige Kies, Melissa J Karau, Robin Patel, Haluk Beyenal","doi":"10.1128/spectrum.01762-25","DOIUrl":"https://doi.org/10.1128/spectrum.01762-25","url":null,"abstract":"<p><p>Biofilms hinder wound infection healing, making wound infections a healthcare challenge for which innovative treatments are needed. A 1.77 cm<sup>2</sup> electrochemical bandage (e-bandage), which generates the biocide hypochlorous acid (HOCl), has shown promising anti-biofilm activity <i>in vitro</i>, <i>ex vivo</i>, and <i>in vivo</i>. The e-bandage is a three-electrode system operationalized by a hydrogel. In addition to providing a conductive electrolyte for the electrodes, the hydrogel provides a protective barrier for the wound. How different hydrogels impact e-bandage functionality is not completely defined. Here, the <i>in vitro</i> activity of seven clinically available hydrogels (xanthan gum, 3M, Duoderm, Prontosan, Purilon, Skintegrity, and Solosite) was evaluated with 1.77 cm<sup>2</sup> HOCl-generating e-bandages using a potentiostat with a multiplexer in a membrane biofilm model against methicillin-resistant <i>Staphylococcus aureus</i> IDRL-6169 and <i>Acinetobacter baumannii</i> ATCC-17978. When applied with polarized HOCl-producing e-bandages, all evaluated hydrogels except Solosite yielded ≥5.5 log<sub>10</sub>CFU/cm<sup>2</sup> reductions in bacterial quantities after 6 h of treatment, with most being below the detection limit at that time point. Prontosan exhibited antibacterial activity independent of e-bandage. Results of this study inform the selection of clinically available hydrogels that may be suitable for use with a 1.77 cm<sup>2</sup> HOCl-producing e-bandage.</p><p><strong>Importance: </strong>In this study, it was shown that some clinically available hydrogels, combined with a 1.77 cm<sup>2</sup> HOCl-generating electrochemical bandage, deliver time-dependent antimicrobial activity against methicillin-resistant <i>Staphylococcus aureus</i> and <i>Acinetobacter baumannii</i> biofilms, offering a potential approach to treat wound infections, including those caused by antimicrobial-resistant bacteria.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0176225"},"PeriodicalIF":3.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081125","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}
引用次数: 0
Comprehensive genomic analysis of antibiotic resistance plasmids in animal-associated Staphylococcus aureus in France. 法国动物相关金黄色葡萄球菌抗生素耐药质粒的综合基因组分析。
IF 3.8 2区 生物学
Microbiology spectrum Pub Date : 2025-09-18 DOI: 10.1128/spectrum.00772-25
Rachel Contarin, Séverine Murri, Antoine Drapeau, Tom Cayssials, Jean-Yves Madec, Emilie Dordet-Frisoni, Marisa Haenni
{"title":"Comprehensive genomic analysis of antibiotic resistance plasmids in animal-associated <i>Staphylococcus aureus</i> in France.","authors":"Rachel Contarin, Séverine Murri, Antoine Drapeau, Tom Cayssials, Jean-Yves Madec, Emilie Dordet-Frisoni, Marisa Haenni","doi":"10.1128/spectrum.00772-25","DOIUrl":"https://doi.org/10.1128/spectrum.00772-25","url":null,"abstract":"<p><p>In <i>Staphylococcus aureus</i>, an animal pathogen and zoonotic agent, plasmids play a pivotal role in the acquisition and spread of antibiotic resistance genes (ARGs). This study investigated the plasmid content of 329 <i>S</i>. <i>aureus</i> isolates from livestock and companion animals collected in France between 2010 and 2021. Plasmids (<i>n</i> = 211) were identified from 139 isolates. The major families identified-<i>rep7a</i>, <i>rep20</i>, and <i>rep10</i>-were associated with specific resistance genes (<i>str</i>, <i>cat</i>, <i>blaZ</i>, <i>erm</i>(C)) and exhibited widespread horizontal transfer across different <i>S. aureus</i> sequence types (STs) and animal hosts. In temporal analysis, the <i>rep7a</i>/str and <i>rep7a</i>/<i>cat</i> plasmids circulating in horses were progressively replaced by a <i>rep7a</i> plasmid carrying both <i>str</i> and <i>cat</i> genes. The study also highlighted the presence of mosaic plasmids, which combined elements from different bacterial species/genera, confirming the broad host range of <i>S. aureus</i> plasmids and their ability to acquire ARGs from diverse sources. Moreover, the occurrence of hybrid plasmids (carrying multiple <i>rep</i> genes) underscores the plasticity of these vectors of ARGs. This study emphasizes the need to investigate the mechanisms driving the spread and persistence of antibiotic-resistant plasmids in <i>S. aureus</i>, with a view to developing strategies aimed at combating antibiotic resistance.</p><p><strong>Importance: </strong>The spread of antibiotic resistance in <i>Staphylococcus aureus</i> is a growing concern, particularly in animals that can serve as reservoirs for resistant strains. This study highlights the crucial role of plasmids in transmitting resistance genes among different animal hosts and <i>S. aureus</i> lineages. The characterization of 329 isolates collected over 10 years revealed how certain plasmid families are associated with specific resistance genes and how they evolve over time. The occurrence of mosaic and hybrid plasmids further underscores the ability of <i>S. aureus</i> to acquire resistance from diverse bacterial sources. These findings provide key insights into the mechanisms shaping antibiotic resistance in this pathogen and emphasize the fact that understanding plasmid-driven resistance is essential for developing effective interventions to limit the spread of multidrug-resistant <i>S. aureus</i> in both veterinary and human medicine.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0077225"},"PeriodicalIF":3.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081102","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}
引用次数: 0
Physiological and metabolic responses of Zymomonas mobilis to lignocellulosic hydrolysate. 活动单胞菌对木质纤维素水解物的生理和代谢反应。
IF 3.8 2区 生物学
Microbiology spectrum Pub Date : 2025-09-17 DOI: 10.1128/spectrum.00610-25
Julio Rivera Vazquez, Edna Trujillo, Zach Wenger, Michael Botts, Joshua J Coon, Daniel Amador-Noguez
{"title":"Physiological and metabolic responses of <i>Zymomonas mobilis</i> to lignocellulosic hydrolysate.","authors":"Julio Rivera Vazquez, Edna Trujillo, Zach Wenger, Michael Botts, Joshua J Coon, Daniel Amador-Noguez","doi":"10.1128/spectrum.00610-25","DOIUrl":"https://doi.org/10.1128/spectrum.00610-25","url":null,"abstract":"<p><p><i>Zymomonas mobilis</i> is a promising biocatalyst for the sustainable conversion of lignocellulosic sugars into biofuels and bioproducts, yet its response to lignocellulosic hydrolysates remains poorly understood. Here, we investigate the physiological response of <i>Z. mobilis</i> to ammonia fiber expansion (AFEX)-pretreated switchgrass hydrolysate using a systems-level approach integrating LC-MS/MS-based lipidomics and shotgun proteomics. Growth on hydrolysate induced substantial shifts in fatty acid and membrane phospholipid composition, alongside broad proteomic remodeling. Notably, <i>Z. mobilis</i> exhibited a stress response characterized by the upregulation of heat shock proteins and efflux transporters and the downregulation of cell motility proteins. Unexpectedly, hydrolysate exposure also led to a robust upregulation of the Entner-Doudoroff pathway, the ethanol fermentation pathway, and other central carbon metabolism enzymes, indicating a substantial cellular investment potentially driven by additional nutrient availability in hydrolysate. These findings provide new insights into the metabolic adaptations of <i>Z. mobilis</i> to lignocellulosic hydrolysates, informing strategies to enhance its biofuel production capabilities.IMPORTANCEBiomass pretreatment processes release fermentable sugars from lignocellulosic biomass, but they also generate inhibitors that can impact microbial metabolism. This study provides a systems-level evaluation of how <i>Zymomonas mobilis</i> responds to hydrolysate stress, revealing distinct physiological and lipid membrane remodeling responses. While some stress responses overlap with those induced by ethanol and isobutanol toxicity, both valuable biofuels, hydrolysate exposure elicits unique metabolic shifts. These findings offer valuable insights for engineering <i>Z. mobilis</i> strains with improved tolerance and performance for efficient bioconversion of lignocellulosic hydrolysates into biofuels and bioproducts.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0061025"},"PeriodicalIF":3.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075504","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}
引用次数: 0
Streptomyces huangiella sp. nov., an endophytic actinomycete isolated from Pheretima aspergillum, a promising candidate for biological pathogen control. 黄链霉菌(Streptomyces huangiella sp. nov.)是一种从曲霉霉中分离出来的内生放线菌,是一种很有前途的生物病原体防治候选菌。
IF 3.8 2区 生物学
Microbiology spectrum Pub Date : 2025-09-17 DOI: 10.1128/spectrum.00717-25
Dan Huang, Jinli Tan, Jingyang Liao, Liuchong Zhu, Xiang Zhang, Donghua Feng, Wenbin Liu, Xiaobao Jin
{"title":"<i>Streptomyces huangiella</i> sp. nov., an endophytic actinomycete isolated from <i>Pheretima aspergillum<b>,</b></i> a promising candidate for biological pathogen control.","authors":"Dan Huang, Jinli Tan, Jingyang Liao, Liuchong Zhu, Xiang Zhang, Donghua Feng, Wenbin Liu, Xiaobao Jin","doi":"10.1128/spectrum.00717-25","DOIUrl":"https://doi.org/10.1128/spectrum.00717-25","url":null,"abstract":"<p><p><i>Pheretima aspergillum</i> (E. Perrier) is an annelid of the genus <i>Pheretima</i> in the family Megascolecidae, a species of earthworm, whose dried body (Guang Dilong) is a traditional Chinese animal medicine. A new actinobacterium strain, named HD1123-B1<sup>T</sup>, was isolated from the gut contents of <i>Pheretima aspergillum</i> caught in the wild in Guangzhou, China. Phylogenetic analysis based on 16S rRNA gene sequences revealed that the strain was primarily identified as a member of the genus <i>Streptomyces</i>, sharing more than 98% sequence identity to <i>Streptomyces endocoffeicus</i> CA3R110<sup>T</sup> (98.80%), <i>Streptomyces coffeae</i> CA1R205<sup>T</sup> (98.47%), and <i>Streptomyces iranensis</i> HM35<sup>T</sup> (97.93%). The whole genome size of strain HD1123-B1<sup>T</sup> was approximately 8.9 Mbp, with 7,464 predicted genes and 71.42 mol% DNA C+G content. Comparative genomic analyses based on digital DNA-DNA hybridization (dDDH) and average nucleotide identity (ANI) values revealed that strain HD1123-B1<sup>T</sup> represents a novel species within the genus <i>Streptomyces</i>. Additionally, 38 biosynthetic gene clusters for secondary metabolites were also predicted in the genome of strain HD1123-B1<sup>T</sup>. Based on LC-MS/MS analysis, the nigericin biosynthesis gene cluster has been completely characterized. The ethyl acetate crude extract of strain HD1123-B1<sup>T</sup> exhibited remarkable antibacterial activity against gram-positive bacteria (methicillin-resistant <i>Staphylococcus aureus</i> ATCC 25213, etc) and gram-negative bacteria <i>Ralstonia solanacearum</i> GIM 1.70. Based on these results, HD1123-B1<sup>T</sup> could be confirmed as an isolate that represents a novel species of the genus <i>Streptomyces</i>, for which the name <i>Streptomyces huangiella</i> sp. nov. is proposed.</p><p><strong>Importance: </strong>As the largest genus of the phylum Actinomycetes, <i>Streptomyces</i> is a kind of microbial resources with great practical and economic value. Due to their unique physiological properties and metabolic capacity, <i>Streptomyces</i> have become an important source of bioactive compounds in the world and play an indispensable role in medical and industrial fields. With the advancement of molecular biology and genomics, researchers can more deeply explore the metabolic potential of Actinomycetes, discovering and developing new biologically active compounds. These new compounds may possess various biological activities, such as antibacterial, antiviral, antifungal, and antiparasitic properties, further promoting the development of medicine and related industries. Based on genomic analysis and antibacterial activity, the strain HD1123-B1<sup>T</sup> was indicated to be a promising candidate for biological pathogen control.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0071725"},"PeriodicalIF":3.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075801","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}
引用次数: 0
Genetic characterization of zoonotic Dirofilaria asiatica in Cambodian dogs through nanopore metabarcoding. 通过纳米孔元条形码分析柬埔寨犬人畜共患亚洲dirofilia的遗传特征。
IF 3.8 2区 生物学
Microbiology spectrum Pub Date : 2025-09-17 DOI: 10.1128/spectrum.01990-25
Lucas G Huggins, Ushani Atapattu, Virak Khieu, Rebecca Traub, Vito Colella
{"title":"Genetic characterization of zoonotic <i>Dirofilaria asiatica</i> in Cambodian dogs through nanopore metabarcoding.","authors":"Lucas G Huggins, Ushani Atapattu, Virak Khieu, Rebecca Traub, Vito Colella","doi":"10.1128/spectrum.01990-25","DOIUrl":"https://doi.org/10.1128/spectrum.01990-25","url":null,"abstract":"<p><p>Filarioid nematodes are harmful vector-borne pathogens that afflict humans and other animals, with numerous species transmissible from animals to humans, i.e., zoonotic. In the last decade, one zoonotic filarioid, previously named <i>Dirofilaria</i> sp. Hong Kong genotype has been increasingly found as a cause of disease in people traveling from South Asia and has recently been characterized as a novel species: <i>Dirofilaria asiatica</i>. Nonetheless, the epidemiology of this parasite in Asia remains poorly understood. Therefore, with the aid of a novel pan-filarioid nanopore-based metabarcoding assay, we aimed to elucidate the epidemiology of dirofilariosis in Cambodia. We tested 504 canine blood samples collected from five regions and used the cytochrome c oxidase (<i>cox1</i>) gene sequences obtained to conduct phylogenetic analyzes. We found no evidence of the canine heartworm <i>Dirofilaria immitis</i> nor <i>Dirofilaria repens</i> in the country. Conversely, we detected <i>D. asiatica</i> and genetically characterized it from the eastern district of Tbong Khmum at a local prevalence of 4% (95% CI = 1.6%-9.8%), an area just ~100 km northeast of the country's capital, Phnom Penh. We also detected <i>Acanthocheilonema reconditum</i> from 0.2% of dogs sampled (95% CI = 0%-1%). Phylogenetic and haplotype network analyzes of Cambodian <i>D. asiatica</i> sequences clustered with strong support to those found from canines and humans in Bhutan, Hong Kong, India, and Sri Lanka. This genetic characterization of <i>D. asiatica</i> in Cambodia highlights the need for further epidemiological research into human filariases in Cambodia, given the zoonotic nature of this parasite and that mass drug administration targeting filarioids is no longer conducted in the country.IMPORTANCEParasitic filarioid nematodes are transmitted by blood-sucking arthropods and can cause significant disease in animals and humans (i.e., zoonotic). One such zoonotic filarioid (<i>Dirofilaria asiatica</i>) that has recently been characterized has been found responsible for a growing number of cases of human filariases, particularly in individuals who live in or have traveled to South and Southeast Asia. <i>D. asiatica</i> predominantly infects dogs, and therefore, to better understand this parasite's distribution, we tested 504 dogs from five regions of Cambodia using an advanced diagnostic approach. We found that the local prevalence of <i>D. asiatica</i> in dogs in the eastern district of Tbong Khmum was 4%. Given that mass drug administration programs to control human-infecting filarioid nematodes in Cambodia have stopped, this first detection of <i>D. asiatica</i> in Cambodia is alarming, given its potential to cause disease in vulnerable cohabiting people.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0199025"},"PeriodicalIF":3.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075794","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}
引用次数: 0
Species distribution of nontuberculous mycobacteria isolated from respiratory specimens at a tertiary care hospital in South Korea, 2017-2022. 2017-2022年韩国某三级医院呼吸道标本分离非结核分枝杆菌的种类分布
IF 3.8 2区 生物学
Microbiology spectrum Pub Date : 2025-09-17 DOI: 10.1128/spectrum.00554-25
Tae Yeul Kim, Jeong Su Park, Minhee Kang, Byung Woo Jhun, Hee Jae Huh, Nam Yong Lee, Sue Shin
{"title":"Species distribution of nontuberculous mycobacteria isolated from respiratory specimens at a tertiary care hospital in South Korea, 2017-2022.","authors":"Tae Yeul Kim, Jeong Su Park, Minhee Kang, Byung Woo Jhun, Hee Jae Huh, Nam Yong Lee, Sue Shin","doi":"10.1128/spectrum.00554-25","DOIUrl":"https://doi.org/10.1128/spectrum.00554-25","url":null,"abstract":"<p><p>The clinical relevance and drug resistance patterns of nontuberculous mycobacteria (NTM) vary by species. This study investigated the species distribution of NTM isolated from respiratory specimens at a tertiary care hospital in South Korea from 2017 to 2022. A retrospective analysis was conducted on laboratory data from respiratory specimens submitted for acid-fast bacilli culture. NTM isolates were identified using a line probe assay, and those unidentifiable at the species or complex level underwent multigene sequencing of the 16S rRNA, <i>rpoB</i>, and <i>hsp65</i> genes. Among all mycobacterial isolates, the proportion of NTM showed an increasing trend, rising from 87.4% in 2017 to 93.3% in 2022. The eight most common species were <i>M. avium</i> complex (61.9%), <i>M. abscessus</i> (14.2%), <i>M. fortuitum</i> complex (8.4%), <i>M. gordonae</i> (5.3%), <i>M. simiae</i> complex (3.4%), <i>M. kansasii</i> complex (1.9%), <i>M. terrae</i> complex (1.5%), and <i>M. chelonae</i> (1.2%), accounting for 97.7% of all NTM isolates. Among the remaining isolates (2.3%, <i>n</i> = 169), 161 were classified into 24 species and groups, the majority with proportions below 0.1%. Two of the eight isolates that could not be identified at the species or group level despite multigene sequencing underwent whole-genome sequencing, which suggested they likely represent novel <i>Mycobacterium</i> species. This study provides valuable insights into the distribution of NTM species, particularly rarely encountered species, isolated from respiratory specimens in South Korea. These findings may aid in optimizing diagnostic strategies and selecting appropriate treatment options.IMPORTANCEGiven the significant variations in clinical relevance and drug resistance patterns among nontuberculous mycobacteria (NTM) species, understanding their geographic distribution is essential for selecting appropriate treatment options and improving patient outcomes. This study investigated the distribution of NTM species isolated from respiratory specimens at a tertiary care hospital in South Korea from 2017 to 2022. Our findings revealed an increasing proportion of NTM, with <i>M. avium</i> complex and <i>M. abscessus</i> remaining predominant. Additionally, we identified 24 rarely encountered species and groups, along with two strains that likely represent novel <i>Mycobacterium</i> species. Our study advances the understanding of the evolving NTM epidemiology in South Korea, contributing to the optimization of diagnostic strategies and improvement of patient management.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0055425"},"PeriodicalIF":3.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075556","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}
引用次数: 0
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