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Anti-Human Endogenous Retrovirus and Anti-Myelin Oligodendrocyte Glycoprotein Humoral Response in Cerebrospinal Fluid of Multiple Sclerosis Patients: A Case Control Study. 多发性硬化症患者脑脊液抗人内源性逆转录病毒和抗髓鞘少突胶质细胞糖蛋白体液反应:一项病例对照研究。
IF 1.9 4区 医学
Microbiology and Immunology Pub Date : 2025-07-22 DOI: 10.1111/1348-0421.70003
Karin C Garcia, Samuel N Santos, Bruna R Flose, Maria A Juliano, Renan B Domingues, Lucas M Neves, Guilherme José Costa Silva, Liã B Arruda, Augusto C Penalva-de-Oliveira, Sandro L de Andrade Matas, Marina T Shio, Luiz H da Silva Nali
{"title":"Anti-Human Endogenous Retrovirus and Anti-Myelin Oligodendrocyte Glycoprotein Humoral Response in Cerebrospinal Fluid of Multiple Sclerosis Patients: A Case Control Study.","authors":"Karin C Garcia, Samuel N Santos, Bruna R Flose, Maria A Juliano, Renan B Domingues, Lucas M Neves, Guilherme José Costa Silva, Liã B Arruda, Augusto C Penalva-de-Oliveira, Sandro L de Andrade Matas, Marina T Shio, Luiz H da Silva Nali","doi":"10.1111/1348-0421.70003","DOIUrl":"https://doi.org/10.1111/1348-0421.70003","url":null,"abstract":"<p><p>It is believed that human endogenous retrovirus (HERV)-W plays a fundamental role in multiple sclerosis (MS) pathogenesis, probably by inducing humoral and cellular immunopathological response. HERVs present regions of similarity to myelin oligodendrocyte glycoprotein (MOG) and therefore could induce autoimmunity through the mechanism of molecular mimicry via cross-humoral response. This study aimed to evaluate the impact of HERV-mediated humoral response among MS patients by assessing IgG antibody levels of HERV-W and K in cerebrospinal fluid (CSF). CSF samples were collected from MS patients (n = 25) and idiopathic intracranial hypertension (IIH) patients (n = 25). Serum samples from MS group (n = 25) were also analyzed. CSF samples were assessed for global and differential cell counts, analytical biochemistry, and oligoclonal bands analysis. ELISA was used to determine the serum and intrathecal (CSF) presence and concentration of anti-MOG, anti-HERV-W-env, and anti-HERV-K-pol antibodies. ELISA findings revealed higher concentrations of anti-MOG and HERV-W IgG in MS compared to IIH (p < 0.01 and p = 0.0142 respectively), while HERV-K IgG showed concentration to three HERV-K peptides (p < 0.01). A positive correlation was also observed between serum and CSF antibody concentration for MOG (r = 0.47 p = 0.01), HERV-W (r = 0.72 p < 0.01), and three HERV-K peptides (r = 0.49, 0.57, 0.61 and p = 0.0126, p < 0.01, and p < 0.01, respectively) among MS patients. Our findings revealed high concentrations of anti-HERV-K and -W antibodies in serum and CSF among MS patients, suggesting a possible role of humoral immunopathological response. In addition, the positive correlation between serum and CSF antibody concentration indicates the potential application of serum levels of anti-HERV and anti-MOG as biomarkers for MS.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Therapeutic Potential of Lactobacillus plantarum ATG-K2 in Bacterial Vaginosis: In Vitro and In Vivo Evidence. 植物乳杆菌ATG-K2在细菌性阴道病中的治疗潜力:体外和体内证据。
IF 1.9 4区 医学
Microbiology and Immunology Pub Date : 2025-07-18 DOI: 10.1111/1348-0421.70001
Yeon-Hwa Park, Juyi Park, Ye-Won Kang, Jihee Kang
{"title":"Therapeutic Potential of Lactobacillus plantarum ATG-K2 in Bacterial Vaginosis: In Vitro and In Vivo Evidence.","authors":"Yeon-Hwa Park, Juyi Park, Ye-Won Kang, Jihee Kang","doi":"10.1111/1348-0421.70001","DOIUrl":"https://doi.org/10.1111/1348-0421.70001","url":null,"abstract":"<p><p>Bacterial vaginosis (BV) is characterized by reduced vaginal lactobacilli and pathogenic bacteria proliferation, leading to symptoms such as vaginal epithelial cell detachment and unpleasant odor, along with various complications. Most Lactobacillus species play a crucial role in not only inhibiting BV, but also maintaining vaginal health. We aimed to determine whether Lactobacillus plantarum ATG-K2 has therapeutic and preventive effects against Gardnerella vaginalis (GV), a representative pathogen of BV. In vitro cell assays confirmed that ATG-K2 clusters within cells without cytotoxic effects and inhibits both the cytotoxicity and GV adhesion. Furthermore, biofilm formation assays using crystal violet revealed that ATG-K2 disrupts GV-formed biofilms. In GV-induced BV mouse models, ATG-K2 reduced clue cell formation and sialidase activity, thereby addressing the key aspects of BV. Additionally, when ATG-K2 was administered, the measurement of GV DNA within the vaginal tissue revealed a reduction in GV. In conclusion, ATG-K2 holds promise as a therapeutic agent for BV by inhibiting GV colonization and the associated pathology, potentially offering an alternative to antibiotics.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Functional Rewiring of Three Pneumococcal Proteins Into Plasminogen Binders. 三种肺炎球菌蛋白重组成纤溶酶原结合物的功能研究。
IF 1.9 4区 医学
Microbiology and Immunology Pub Date : 2025-07-13 DOI: 10.1111/1348-0421.70000
Yoshihito Yasui, Satoru Hirayama, Hisanori Domon, Koichi Tabeta, Yutaka Terao
{"title":"Functional Rewiring of Three Pneumococcal Proteins Into Plasminogen Binders.","authors":"Yoshihito Yasui, Satoru Hirayama, Hisanori Domon, Koichi Tabeta, Yutaka Terao","doi":"10.1111/1348-0421.70000","DOIUrl":"https://doi.org/10.1111/1348-0421.70000","url":null,"abstract":"<p><p>To investigate the mechanisms underlying pneumococcal infection, a proteomic analysis was previously conducted to identify pneumococcal proteins in infected mouse samples. In the present study, we characterized three proteins, ATP synthase subunit beta (AtpD), ABC transporter transmembrane protein (Vex3), and fructose bisphosphate aldolase (Fba), which bind to human plasminogen and subsequently facilitate its conversion to plasmin by tissue-type plasminogen activator. These findings suggest that Streptococcus pneumoniae might exploit the proteolytic activity of plasmin to promote infection and highlights the potential importance of plasminogen-binding capacity in the pathogenesis of pneumococcal infection.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Circulating Cell-Free DNA of Bovine Leukemia Virus: A Promising Biomarker for Enzootic Bovine Leukosis. 牛白血病病毒循环无细胞DNA:一种有前途的牛地方性白血病生物标志物。
IF 1.9 4区 医学
Microbiology and Immunology Pub Date : 2025-07-07 DOI: 10.1111/1348-0421.13231
M Ishrat Jahan, Toshiaki Inenaga, Sakurako Makimoto, Md Belal Hossain, Yuka Matsuoka, Sharmin Nahar Sithi, Samiul Alam Rajib, Arif Nur Muhammad Ansori, Kenji Sugata, Kazuhiko Imakawa, Tomoko Kobayashi, Yorifumi Satou
{"title":"Circulating Cell-Free DNA of Bovine Leukemia Virus: A Promising Biomarker for Enzootic Bovine Leukosis.","authors":"M Ishrat Jahan, Toshiaki Inenaga, Sakurako Makimoto, Md Belal Hossain, Yuka Matsuoka, Sharmin Nahar Sithi, Samiul Alam Rajib, Arif Nur Muhammad Ansori, Kenji Sugata, Kazuhiko Imakawa, Tomoko Kobayashi, Yorifumi Satou","doi":"10.1111/1348-0421.13231","DOIUrl":"https://doi.org/10.1111/1348-0421.13231","url":null,"abstract":"<p><p>Bovine leukemia virus (BLV) causes Enzootic bovine leukosis (EBL) in approximately 1%-5% of infected cattle after a long latent period. Few biomarkers effectively distinguish non-EBL from EBL cattle. Given the rapid turnover of tumor cells, we hypothesized that cell-free DNA (cfDNA) in plasma could serve as a more effective biomarker for EBL diagnosis. We measured the proviral load (PVL) in whole blood and plasma by quantitative PCR targeting LTR and pol. Consistent with previous reports, PVL levels in whole blood in EBL cattle were generally higher than those in non-EBL with some overlap between these two groups. In contrast, PVL in plasma clearly distinguished non-EBL from EBL ones. The receiver operating characteristic analysis showed plasma PVL perfectly discriminated EBL from non-EBL (100% sensitivity and specificity), while whole-blood PVL achieved 70% sensitivity and 30% specificity. Additionally, length of PCR products played a role in PVL detection sensitivity in plasma. We compared the complete BLV sequence between genomic DNA from lymphoma tissue and cfDNA in plasma and found that the predominant BLV sequences were highly similar between them. By assessing the major tumor clone burden based on unique integration sites, we found that BLV cfDNA derived more from tumor clones in the tissues than from peripheral blood mononuclear cells (PBMCs). These data support the idea that BLV in cfDNA primarily originates from tumor cells in EBL cattle. These findings demonstrated that cfDNA could be a better indicator for EBL diagnosis, improving early detection and more timely intervention to reduce the economic loss in the meat and dairy industry.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Issue Information – Cover 发行资料-封面
IF 1.9 4区 医学
Microbiology and Immunology Pub Date : 2025-07-03 DOI: 10.1111/1348-0421.13143
{"title":"Issue Information – Cover","authors":"","doi":"10.1111/1348-0421.13143","DOIUrl":"https://doi.org/10.1111/1348-0421.13143","url":null,"abstract":"<p><b>Cover photograph</b>: The three pillars of horizontal gene transfer of ARGs. (1) Conjugation. ARG-carrying plasmids with self-transmissibility are transferred from donor cells to recipient cells upon cell-to-cell contact. As a result, identical plasmids are ultimately present in both donor and recipient cells. (2) Transformation. DNA fragments carrying ARGs, released upon donor cell death, are taken up by recipient cells and integrated into their chromosomes via homologous recombination. (3-1) Specialized transduction. Phage particles containing structural genes and accessory ARGs are released from donor cells and attach to recipient cells. The phage structural genes and accessory ARGs are then injected into the recipient cells, and they are subsequently integrated into the recipient's chromosome. (3-2) Generalized transduction. Phage particles containing host cell DNA, including ARGs, are released from donor cells and attach to recipient cells. The donor-derived genes including ARGs are then injected into the recipient cells and subsequently integrated into the recipient's chromosome. <i>Microbiol Immunol: 69:367-376</i>. Article link here\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"69 7","pages":"i-ii"},"PeriodicalIF":1.9,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1348-0421.13143","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Virulence Potential of Nonclinical Vibrio parahaemolyticus Isolates From Vietnam: Evidence for Functional T3SS2-Mediated Enterotoxicity. 越南非临床副溶血性弧菌分离株的毒力潜力:功能性t3ss2介导的肠毒性证据
IF 1.9 4区 医学
Microbiology and Immunology Pub Date : 2025-06-29 DOI: 10.1111/1348-0421.13229
Moses Lorenzo Akyeh, Masatomo Morita, Sarunporn Tandhavanant, Ballamoole Krishna Kumar, Pham Hong Quynh Anh, Tran Thi Hien, Pham Tuyet Ngoc Linh, Nguyen Dong Tu, Vu Thi Mai Hien, Taichiro Takemura, Hiroyuki Terashima, Hirotaka Hiyoshi, Kazuhisa Okada, Toshio Kodama
{"title":"Virulence Potential of Nonclinical Vibrio parahaemolyticus Isolates From Vietnam: Evidence for Functional T3SS2-Mediated Enterotoxicity.","authors":"Moses Lorenzo Akyeh, Masatomo Morita, Sarunporn Tandhavanant, Ballamoole Krishna Kumar, Pham Hong Quynh Anh, Tran Thi Hien, Pham Tuyet Ngoc Linh, Nguyen Dong Tu, Vu Thi Mai Hien, Taichiro Takemura, Hiroyuki Terashima, Hirotaka Hiyoshi, Kazuhisa Okada, Toshio Kodama","doi":"10.1111/1348-0421.13229","DOIUrl":"https://doi.org/10.1111/1348-0421.13229","url":null,"abstract":"<p><p>Vibrio parahaemolyticus is a leading cause of seafood-borne gastroenteritis worldwide, and its pathogenic strains typically harbor thermostable direct hemolysin (TDH) and type III secretion system 2 (T3SS2). Although these virulence factors are associated primarily with clinical isolates, their presence in nonclinical environmental and food isolates raises concerns about their potential infection risk. In this study, we investigated the pathogenic potential of nonclinical V. parahaemolyticus isolates from Vietnam, which share serotypic and genotypic characteristics with pandemic strains. Serotyping and genetic analysis of 56 isolates (35 clinical and 21 nonclinical) revealed that two nonclinical isolates from shrimp and environmental water carried the tdh gene, T3SS2α genes, and pandemic markers that clustered phylogenetically with the pandemic strains. Protein expression assays confirmed that these isolates secreted TDH and the T3SS2 translocator (VopD2) at levels similar to those in the clinical reference strain. Bile exposure induced T3SS2-related gene expression, which suggests a conserved gene regulatory mechanism. Enterotoxicity evaluated using a rabbit ileal loop assay showed that two nonclinical isolates induced significant fluid accumulation. Genetic deletion and complementation experiments confirmed that T3SS2 was essential for enterotoxicity. These findings provide the first experimental evidence that nonclinical pandemic strains of V. parahaemolyticus possess functional enteric virulence mechanisms and suggest their potential as infection sources in endemic regions.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Bifidobacterium bifidum G9-1 Survives in the Intestinal Environment and Influences the Gut Microbiota Despite the Presence of Antimicrobials. 尽管存在抗菌剂,两歧双歧杆菌G9-1在肠道环境中存活并影响肠道微生物群。
IF 1.9 4区 医学
Microbiology and Immunology Pub Date : 2025-06-29 DOI: 10.1111/1348-0421.13230
Haruka Yokota, Yutaka Makizaki, Yoshiki Tanaka, Hiroshi Ohno
{"title":"Bifidobacterium bifidum G9-1 Survives in the Intestinal Environment and Influences the Gut Microbiota Despite the Presence of Antimicrobials.","authors":"Haruka Yokota, Yutaka Makizaki, Yoshiki Tanaka, Hiroshi Ohno","doi":"10.1111/1348-0421.13230","DOIUrl":"https://doi.org/10.1111/1348-0421.13230","url":null,"abstract":"<p><p>Probiotics can help prevent antibiotic-associated diarrhea; however, those lacking antimicrobial resistance may be ineffective during antimicrobial treatment. Here, we aimed to examine the effects of antimicrobials on the probiotic strain Bifidobacterium bifidum G9-1 (BBG9-1). Minimum inhibitory concentrations were determined in vitro by culturing B. bifidum G9-1 with antimicrobials and assessing its viability. For in vivo analysis, germ-free and specific pathogen-free mice were administered B. bifidum G9-1 along with antimicrobials. Gut microbiota composition and viable B. bifidum G9-1 abundance were determined. Bifidobacterium bifidum G9-1 was highly sensitive to antimicrobials in vitro. However, in a complex bacterial environment mimicking the gut environment, the abundance of viable B. bifidum G9-1 was significantly high despite antimicrobial exposure. Dominant bacterial populations were more affected by antimicrobials than nondominant populations, with B. bifidum G9-1 exhibiting increased viability in the presence of diverse bacterial species. In vivo, combined administration of antimicrobials and B. bifidum G9-1 significantly reduced B. bifidum G9-1 abundance in germ-free mice but not in specific pathogen-free mice, where the gut microbiota composition shifted following administration of B. bifidum G9-1. The presence of diverse live bacteria in the intestine promotes the survival of B. bifidum G9-1 and its beneficial effects, even in the presence of antimicrobials. This finding suggests that B. bifidum G9-1, despite lacking intrinsic antimicrobial resistance, can survive and reach the large intestine, maintaining its probiotic function. Therefore, B. bifidum G9-1 can potentially be used for antibiotic-associated diarrhea prevention.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Issue Information – Cover 发行资料-封面
IF 1.9 4区 医学
Microbiology and Immunology Pub Date : 2025-06-08 DOI: 10.1111/1348-0421.13141
{"title":"Issue Information – Cover","authors":"","doi":"10.1111/1348-0421.13141","DOIUrl":"https://doi.org/10.1111/1348-0421.13141","url":null,"abstract":"<p><b>Cover photograph</b>: Circular heat map depicting expression patterns of common differentially expressed kinases in both GSE datasets. <i>Microbiol Immunol: 69:326-338</i>. Article link here\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"69 6","pages":"i-ii"},"PeriodicalIF":1.9,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1348-0421.13141","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144244364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Competitive Binding of Pseudomonas aeruginosa to Kelch-Like ECH-Associated Protein 1 Inhibits Nuclear Factor Erythroid 2-Related Factor 2 Ubiquitination and Suppresses Ferroptosis in Macrophages. 铜绿假单胞菌与kelch样ech相关蛋白1的竞争结合抑制巨噬细胞核因子红系2相关因子2泛素化并抑制铁凋亡
IF 1.9 4区 医学
Microbiology and Immunology Pub Date : 2025-06-04 DOI: 10.1111/1348-0421.13228
Yan Zhu, Qingqing Liu, Erdan Lu, Zongyu Li
{"title":"Competitive Binding of Pseudomonas aeruginosa to Kelch-Like ECH-Associated Protein 1 Inhibits Nuclear Factor Erythroid 2-Related Factor 2 Ubiquitination and Suppresses Ferroptosis in Macrophages.","authors":"Yan Zhu, Qingqing Liu, Erdan Lu, Zongyu Li","doi":"10.1111/1348-0421.13228","DOIUrl":"https://doi.org/10.1111/1348-0421.13228","url":null,"abstract":"<p><p>The survival of Pseudomonas aeruginosa (PA) is a major factor in causing chronic or acute lung infections in individuals with compromised immune systems. Being the initial line of defense against infections, macrophages use a variety of tactics to fight intracellular bacteria, which are intimately linked to ferroptosis. It is yet unknown, nevertheless, what function ferroptosis serves in PA-infected macrophages. Initially, we established a macrophage infection model with PA to investigate the infection levels and duration using Cell Counting Kit-8 (CCK-8) and fluorescence microscopy and assessed the intracellular quantity of PA by counting colony forming units (CFUs). Subsequently, changes in ferroptosis-related characteristics in macrophages infected with PA were detected through quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blot analysis, and fluorescence probes. Furthermore, the relationship between PA infection and ferroptosis in macrophages, as well as the specific mechanism regulating nuclear factor erythroid 2-related factor 2 (NRF2) protein stability, was validated by constructing NRF2 knockdown cells. Finally, the binding of PA to Kelch-like ECH-associated protein 1 (KEAP1) in macrophages was detected using Co-Immunoprecipitation (Co-IP) and protein thermal stability analysis. Under optimal conditions (multiplicity of infection (MOI) = 15:1, t = 72 h), it was demonstrated that macrophages infected with PA resisted ferroptosis, as confirmed by ferroptosis-related assays. Subsequent construction of NRF2 knockdown cells showed that PA-mediated resistance of macrophage ferroptosis depended on NRF2. Mechanistically, it was proved that PA stabilized NRF2 protein expression by inhibiting ubiquitin-proteasome-mediated protein degradation and competitively binding to KEAP1. In conclusion, this study demonstrated that PA stabilized NRF2 protein expression in macrophages, inducing resistance to ferroptosis through the ubiquitin-proteasome pathway and competitive binding to KEAP1.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Lytic Transglycosylase Deficiency Increases Susceptibility to β-lactam Antibiotics But Reduces Susceptibility to Vancomycin in Escherichia coli. 裂解转糖基酶缺乏增加大肠杆菌对β-内酰胺类抗生素的敏感性,但降低对万古霉素的敏感性。
IF 1.9 4区 医学
Microbiology and Immunology Pub Date : 2025-05-26 DOI: 10.1111/1348-0421.13227
Takahiko Kimura, Kazuya Ishikawa, Ryosuke Nakagawa, Kazuyuki Furuta, Chikara Kaito
{"title":"Lytic Transglycosylase Deficiency Increases Susceptibility to β-lactam Antibiotics But Reduces Susceptibility to Vancomycin in Escherichia coli.","authors":"Takahiko Kimura, Kazuya Ishikawa, Ryosuke Nakagawa, Kazuyuki Furuta, Chikara Kaito","doi":"10.1111/1348-0421.13227","DOIUrl":"https://doi.org/10.1111/1348-0421.13227","url":null,"abstract":"<p><p>In Staphylococcus aureus, a gram-positive pathogen, vancomycin-resistant strains become susceptible to β-lactam antibiotics, referred to as the \"seesaw effect.\" However, in gram-negative bacteria, the phenomenon is less clear. Here, we analyzed the gene-knockout effects of eight lytic transglycosylases (slt, mltA, mltB, mltC, mltD, mltE, mltF, mltG) on antibiotic sensitivity in Escherichia coli. Knockout of both slt and mltG increased sensitivity to β-lactam antibiotics and reduced sensitivity to vancomycin. The β-lactam antibiotic sensitivity and vancomycin resistance of the slt-knockout mutant were abolished by the introduction of the wild-type slt gene but remained unchanged by the introduction of the mutant slt gene encoding an amino acid substitution variant of the transglycosylase catalytic centre. The double-knockout strain for slt and mltB was more sensitive to ampicillin and more resistant to vancomycin than each single-knockout strain. The double-knockout strain for slt and mltG was more sensitive to ampicillin and more resistant to vancomycin than each single-knockout strain. These results suggest that loss of lytic transglycosylase activity causes β-lactam antibiotic sensitivity and vancomycin resistance in E. coli.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","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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