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Epicatechin gallate and its analogues interact with sortase A and β-lactamase to suppress Staphylococcus aureus virulence.
IF 4.6 2区 医学 Q2 IMMUNOLOGY Pub Date : 2025-03-25 eCollection Date: 2025-01-01 DOI: 10.3389/fcimb.2025.1537564
Fei Teng, Lihui Wang, Jingyao Wen, Zizeng Tian, Guizhen Wang, Liping Peng

Staphylococcus aureus sortase A can anchor virulence proteins, which are responsible for bacterial adhesion, biofilm formation, and inflammation, to the cell membrane surface. The ability of β-lactam antibiotics to combat S. aureus infections is limited by the presence of β-lactamases in this pathogen. In this study, we determined that epicatechin gallate (ECG) and its analogues inhibited the transpeptidase activity of sortase A by interacting with it directly, and the biofilm formation and adhesion abilities of the bacterium decreased after treatment with ECG and its analogues. Additionally, ECG bound to β-lactamase and reduced its ability to hydrolyze nitrocefin. Furthermore, ECG synergized with ampicillin (Amp), enhancing its bactericidal effects and inhibiting the formation of persisters. ECG did not affect the expression of sortase A or β-lactamase but significantly alleviated the cytotoxicity of S. aureus USA300. ECG alone or combined with Amp in vivo improved the survival of mice infected with S. aureus USA300, alleviated pathological tissue damage and pulmonary edema, and reduced the extent of inflammation and level of colonization. The results of this study indicate that the active ingredients of green tea, especially ECG, have the potential to be developed as anti-S. aureus infection agents.

{"title":"Epicatechin gallate and its analogues interact with sortase A and β-lactamase to suppress <i>Staphylococcus aureus</i> virulence.","authors":"Fei Teng, Lihui Wang, Jingyao Wen, Zizeng Tian, Guizhen Wang, Liping Peng","doi":"10.3389/fcimb.2025.1537564","DOIUrl":"https://doi.org/10.3389/fcimb.2025.1537564","url":null,"abstract":"<p><p><i>Staphylococcus aureus</i> sortase A can anchor virulence proteins, which are responsible for bacterial adhesion, biofilm formation, and inflammation, to the cell membrane surface. The ability of β-lactam antibiotics to combat <i>S. aureus</i> infections is limited by the presence of β-lactamases in this pathogen. In this study, we determined that epicatechin gallate (ECG) and its analogues inhibited the transpeptidase activity of sortase A by interacting with it directly, and the biofilm formation and adhesion abilities of the bacterium decreased after treatment with ECG and its analogues. Additionally, ECG bound to β-lactamase and reduced its ability to hydrolyze nitrocefin. Furthermore, ECG synergized with ampicillin (Amp), enhancing its bactericidal effects and inhibiting the formation of persisters. ECG did not affect the expression of sortase A or β-lactamase but significantly alleviated the cytotoxicity of <i>S. aureus</i> USA300. ECG alone or combined with Amp <i>in vivo</i> improved the survival of mice infected with <i>S. aureus</i> USA300, alleviated pathological tissue damage and pulmonary edema, and reduced the extent of inflammation and level of colonization. The results of this study indicate that the active ingredients of green tea, especially ECG, have the potential to be developed as anti-<i>S. aureus</i> infection agents.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1537564"},"PeriodicalIF":4.6,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11975897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Mechanisms and genetic mutations of pyrethroid resistance in Aedes albopictus in the context of urbanization: a case study of Hangzhou, China.
IF 4.6 2区 医学 Q2 IMMUNOLOGY Pub Date : 2025-03-25 eCollection Date: 2025-01-01 DOI: 10.3389/fcimb.2025.1566942
Binbin Jin, Lingya Wei, Tianxiao Duan, Yinghong Wang, Huimin Wang, Hui Jin

Background: The Asian tiger mosquito (Aedes albopictus) serves as a globally significant vector for arboviruses such as dengue, chikungunya, and Zika. The extensive application of pyrethroid insecticides has led to a growing resistance in Ae. albopictus populations, thereby compromising mosquito control initiatives. This study examines the mechanisms underlying pyrethroid resistance and the related genetic mutations in Ae. albopictus within the framework of urbanization, with the objective of informing the development of effective control strategies.

Methods: Ae. albopictus larvae were sampled from five districts in Hangzhou, China, each characterized by different levels of urbanization. Resistance to beta-cypermethrin and permethrin were evaluated utilizing the World Health Organization (WHO) tube test methodology. Molecular analyses were conducted to identify mutations in the voltage-gated sodium channel (VGSC) gene, with a specific focus on the F1534S mutation. The data were subjected to statistical analysis using Fisher's exact test, chi-square test, and Pearson correlation to assess the relationship between resistance levels and urbanization.

Results: Populations of Ae. albopictus in Hangzhou demonstrated substantial resistance to pyrethroids, with mortality rates falling below 90%. Notably, the Binjiang District exhibited the lowest mortality rates, with 20.55% for beta-cypermethrin and 21.21% for permethrin, whereas Chun'an County displayed relatively higher mortality rates of 32.00% and 47.28%, respectively. The F1534S mutation was predominantly observed, with homozygous (S/S) mutations constituting 87.78% and 83.29% of the populations exposed to beta-cypermethrin and permethrin, respectively. Chi-square analyses confirmed a significant association between the F1534S mutation and resistance (P < 0.01). Furthermore, no significant correlation was identified between resistance levels and urbanization rates (P > 0.05), indicating that urbanization is not a primary factor contributing to resistance.

Conclusion: The F1534S mutation is pivotal in conferring pyrethroid resistance in Ae. albopictus. To enhance the effectiveness of mosquito control strategies, it is imperative to incorporate resistance monitoring, insecticide rotation, and non-chemical approaches. Additionally, further research is warranted to investigate alternative resistance mechanisms and the influence of urbanization on mosquito ecology.

{"title":"Mechanisms and genetic mutations of pyrethroid resistance in <i>Aedes albopictus</i> in the context of urbanization: a case study of Hangzhou, China.","authors":"Binbin Jin, Lingya Wei, Tianxiao Duan, Yinghong Wang, Huimin Wang, Hui Jin","doi":"10.3389/fcimb.2025.1566942","DOIUrl":"https://doi.org/10.3389/fcimb.2025.1566942","url":null,"abstract":"<p><strong>Background: </strong>The Asian tiger mosquito (<i>Aedes albopictus</i>) serves as a globally significant vector for arboviruses such as dengue, chikungunya, and Zika. The extensive application of pyrethroid insecticides has led to a growing resistance in <i>Ae. albopictus</i> populations, thereby compromising mosquito control initiatives. This study examines the mechanisms underlying pyrethroid resistance and the related genetic mutations in <i>Ae. albopictus</i> within the framework of urbanization, with the objective of informing the development of effective control strategies.</p><p><strong>Methods: </strong><i>Ae. albopictus</i> larvae were sampled from five districts in Hangzhou, China, each characterized by different levels of urbanization. Resistance to beta-cypermethrin and permethrin were evaluated utilizing the World Health Organization (WHO) tube test methodology. Molecular analyses were conducted to identify mutations in the <i>voltage-gated sodium channel</i> (<i>VGSC</i>) gene, with a specific focus on the F1534S mutation. The data were subjected to statistical analysis using Fisher's exact test, chi-square test, and Pearson correlation to assess the relationship between resistance levels and urbanization.</p><p><strong>Results: </strong>Populations of <i>Ae. albopictus</i> in Hangzhou demonstrated substantial resistance to pyrethroids, with mortality rates falling below 90%. Notably, the Binjiang District exhibited the lowest mortality rates, with 20.55% for beta-cypermethrin and 21.21% for permethrin, whereas Chun'an County displayed relatively higher mortality rates of 32.00% and 47.28%, respectively. The F1534S mutation was predominantly observed, with homozygous (S/S) mutations constituting 87.78% and 83.29% of the populations exposed to beta-cypermethrin and permethrin, respectively. Chi-square analyses confirmed a significant association between the F1534S mutation and resistance (<i>P</i> < 0.01). Furthermore, no significant correlation was identified between resistance levels and urbanization rates (<i>P</i> > 0.05), indicating that urbanization is not a primary factor contributing to resistance.</p><p><strong>Conclusion: </strong>The F1534S mutation is pivotal in conferring pyrethroid resistance in <i>Ae. albopictus</i>. To enhance the effectiveness of mosquito control strategies, it is imperative to incorporate resistance monitoring, insecticide rotation, and non-chemical approaches. Additionally, further research is warranted to investigate alternative resistance mechanisms and the influence of urbanization on mosquito ecology.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1566942"},"PeriodicalIF":4.6,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11975946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Gut microbiome differences and disease risk in colorectal cancer relatives and healthy individuals.
IF 4.6 2区 医学 Q2 IMMUNOLOGY Pub Date : 2025-03-24 eCollection Date: 2025-01-01 DOI: 10.3389/fcimb.2025.1573216
Huifen Wang, Weiwei Zhu, Jun Lei, Zhibo Liu, Yudie Cai, Shuaifeng Wang, Ang Li

Given the heightened focus on high-risk populations, this study aimed to provide insights into early susceptibility and preventive strategies for colorectal cancer (CRC) by focusing on high-risk populations. In this research, fecal samples from 1,647 individuals across three discovery cohorts and nine external validation cohorts were sequenced using whole-genome metagenomic sequencing. A prediction model based on random forest was constructed using the nine external cohorts and independently validated with the three discovery cohorts. A disease probability (POD) model based on microbial biomarkers was developed to assess CRC risk. We found that the gut microbiome composition of CRC relatives differed from that of controls, with enrichment of species such as Fusobacterium and Bacteroides and a reduction in beneficial genera like Coprococcus and Roseburia. Additionally, dietary red meat intake emerged as a risk factor. The POD model indicated an elevated risk of CRC in unaffected relatives. The findings suggest that the POD for CRC may be increased in unaffected relatives or individuals living in shared environments, although this difference did not reach statistical significance. Our study introduces a novel framework for assessing the risk of colorectal cancer in ostensibly healthy individuals.

{"title":"Gut microbiome differences and disease risk in colorectal cancer relatives and healthy individuals.","authors":"Huifen Wang, Weiwei Zhu, Jun Lei, Zhibo Liu, Yudie Cai, Shuaifeng Wang, Ang Li","doi":"10.3389/fcimb.2025.1573216","DOIUrl":"10.3389/fcimb.2025.1573216","url":null,"abstract":"<p><p>Given the heightened focus on high-risk populations, this study aimed to provide insights into early susceptibility and preventive strategies for colorectal cancer (CRC) by focusing on high-risk populations. In this research, fecal samples from 1,647 individuals across three discovery cohorts and nine external validation cohorts were sequenced using whole-genome metagenomic sequencing. A prediction model based on random forest was constructed using the nine external cohorts and independently validated with the three discovery cohorts. A disease probability (POD) model based on microbial biomarkers was developed to assess CRC risk. We found that the gut microbiome composition of CRC relatives differed from that of controls, with enrichment of species such as <i>Fusobacterium</i> and <i>Bacteroides</i> and a reduction in beneficial genera like <i>Coprococcus</i> and <i>Roseburia</i>. Additionally, dietary red meat intake emerged as a risk factor. The POD model indicated an elevated risk of CRC in unaffected relatives. The findings suggest that the POD for CRC may be increased in unaffected relatives or individuals living in shared environments, although this difference did not reach statistical significance. Our study introduces a novel framework for assessing the risk of colorectal cancer in ostensibly healthy individuals.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1573216"},"PeriodicalIF":4.6,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Factors affecting dysbiosis of the gut microbiota in the elderly and the progress of interventions in traditional Chinese and Western medicine.
IF 4.6 2区 医学 Q2 IMMUNOLOGY Pub Date : 2025-03-24 eCollection Date: 2025-01-01 DOI: 10.3389/fcimb.2025.1529347
Zhi-Jun Zhang, Ru Gao, Yu-Tong Lu, Zhi-Liang Zuo, Yu-Huan Li, Shan Liu, Si-Yuan Song, Yi Wang, Hongyan Lai

As the population ages, intestinal health in the elderly has become a key area of concern, with gut microbiota dysbiosis emerging as a significant issue. This review summarizes the factors influencing dysbiosis and interventions from both traditional Chinese medicine (TCM) and Western medicine, offering a reference for future research. A comprehensive search of global databases up to March 2024 identified 617 original studies on gut microbiota dysbiosis in individuals aged 65 and older. After applying strict PRISMA guidelines, 20 articles met the inclusion criteria. Key findings are summarized in four areas: 1) the definition and mechanisms of dysbiosis, 2) evaluation tools for gut microbiota imbalance, 3) factors contributing to dysbiosis in the elderly, and 4) pharmacological treatments. Both TCM and Western medicine offer unique advantages in managing gut microbiota dysbiosis, and the choice of intervention should be tailored to the individual's condition. Future research should focus on optimizing integrated TCM and Western medicine approaches to improve outcomes for elderly patients with gut microbiota dysbiosis.

{"title":"Factors affecting dysbiosis of the gut microbiota in the elderly and the progress of interventions in traditional Chinese and Western medicine.","authors":"Zhi-Jun Zhang, Ru Gao, Yu-Tong Lu, Zhi-Liang Zuo, Yu-Huan Li, Shan Liu, Si-Yuan Song, Yi Wang, Hongyan Lai","doi":"10.3389/fcimb.2025.1529347","DOIUrl":"10.3389/fcimb.2025.1529347","url":null,"abstract":"<p><p>As the population ages, intestinal health in the elderly has become a key area of concern, with gut microbiota dysbiosis emerging as a significant issue. This review summarizes the factors influencing dysbiosis and interventions from both traditional Chinese medicine (TCM) and Western medicine, offering a reference for future research. A comprehensive search of global databases up to March 2024 identified 617 original studies on gut microbiota dysbiosis in individuals aged 65 and older. After applying strict PRISMA guidelines, 20 articles met the inclusion criteria. Key findings are summarized in four areas: 1) the definition and mechanisms of dysbiosis, 2) evaluation tools for gut microbiota imbalance, 3) factors contributing to dysbiosis in the elderly, and 4) pharmacological treatments. Both TCM and Western medicine offer unique advantages in managing gut microbiota dysbiosis, and the choice of intervention should be tailored to the individual's condition. Future research should focus on optimizing integrated TCM and Western medicine approaches to improve outcomes for elderly patients with gut microbiota dysbiosis.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1529347"},"PeriodicalIF":4.6,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Investigating the relationship between cycle threshold of SARS-CoV-2 RT-PCR, clinical features, and laboratory data in hospitalized COVID-19 patients in Semnan, Iran.
IF 4.6 2区 医学 Q2 IMMUNOLOGY Pub Date : 2025-03-24 eCollection Date: 2025-01-01 DOI: 10.3389/fcimb.2025.1522375
Mohammad Hassan Kalantar Neyestanaki, Omid Gholizadeh, Saman Yasamineh, Mahdieh Tarahomi, Pegah Pooya, Majid Eslami, Mehdi Dadashpour, Hadi Ghaffari

Introduction: COVID-19, caused by the SARS-CoV-2 virus, has emerged as a global public health crisis. Understanding the factors associated with disease severity and outcomes is crucial for effective patient management. This study aimed to investigate the association between cycle threshold (CT) values, demographic data, medical history, clinical manifestations, and laboratory findings in hospitalized COVID-19 patients in Semnan, Iran.

Methods: A cross-sectional study was conducted on 86 patients with confirmed COVID-19 admitted to two hospitals in Semnan, Iran, between December 2022 and March 2023. Respiratory swab samples were collected RT-PCR was performed, CT values were obtained, and data were collected from medical records, including demographic information, medical history, clinical manifestations, and laboratory results. Statistical analysis was performed using SPSS software.

Results: The study included 86 COVID-19 patients, with a slightly higher representation of females (55.8%) and a mean age of 67.43 years. Pre-existing conditions like hypertension, diabetes mellitus, and ischemic heart disease were prevalent among hospitalized patients. A majority of patients (59.3%) had severe COVID-19, as indicated by lower CT values, while 31.4% exhibited oxygen saturation levels below 90%. Significant differences were observed in FBS, CRP, WBC, Hb, Cr, and SPo2 levels between severe and non-severe patients. Correlation analysis revealed associations between age, CRP, Cr, BUN, FBS, Vitamin D, TG, LDL, HDL, AST, ALP, and SPo2. Reflecting complex interactions between inflammatory markers, organ function, and lipid metabolism in COVID-19 patients.

Conclusion: This study provides valuable insights into the association between CT values, clinical characteristics, and laboratory findings in hospitalized COVID-19 patients. The findings underscore the importance of CT values in assessing disease severity and potential prognostication. Further research is warranted to validate these findings in larger and more diverse patient populations.

{"title":"Investigating the relationship between cycle threshold of SARS-CoV-2 RT-PCR, clinical features, and laboratory data in hospitalized COVID-19 patients in Semnan, Iran.","authors":"Mohammad Hassan Kalantar Neyestanaki, Omid Gholizadeh, Saman Yasamineh, Mahdieh Tarahomi, Pegah Pooya, Majid Eslami, Mehdi Dadashpour, Hadi Ghaffari","doi":"10.3389/fcimb.2025.1522375","DOIUrl":"10.3389/fcimb.2025.1522375","url":null,"abstract":"<p><strong>Introduction: </strong>COVID-19, caused by the SARS-CoV-2 virus, has emerged as a global public health crisis. Understanding the factors associated with disease severity and outcomes is crucial for effective patient management. This study aimed to investigate the association between cycle threshold (CT) values, demographic data, medical history, clinical manifestations, and laboratory findings in hospitalized COVID-19 patients in Semnan, Iran.</p><p><strong>Methods: </strong>A cross-sectional study was conducted on 86 patients with confirmed COVID-19 admitted to two hospitals in Semnan, Iran, between December 2022 and March 2023. Respiratory swab samples were collected RT-PCR was performed, CT values were obtained, and data were collected from medical records, including demographic information, medical history, clinical manifestations, and laboratory results. Statistical analysis was performed using SPSS software.</p><p><strong>Results: </strong>The study included 86 COVID-19 patients, with a slightly higher representation of females (55.8%) and a mean age of 67.43 years. Pre-existing conditions like hypertension, diabetes mellitus, and ischemic heart disease were prevalent among hospitalized patients. A majority of patients (59.3%) had severe COVID-19, as indicated by lower CT values, while 31.4% exhibited oxygen saturation levels below 90%. Significant differences were observed in FBS, CRP, WBC, Hb, Cr, and SPo2 levels between severe and non-severe patients. Correlation analysis revealed associations between age, CRP, Cr, BUN, FBS, Vitamin D, TG, LDL, HDL, AST, ALP, and SPo2. Reflecting complex interactions between inflammatory markers, organ function, and lipid metabolism in COVID-19 patients.</p><p><strong>Conclusion: </strong>This study provides valuable insights into the association between CT values, clinical characteristics, and laboratory findings in hospitalized COVID-19 patients. The findings underscore the importance of CT values in assessing disease severity and potential prognostication. Further research is warranted to validate these findings in larger and more diverse patient populations.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1522375"},"PeriodicalIF":4.6,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
2bRAD-M reveals differences in microbial communities between Modic changes and disc herniation.
IF 4.6 2区 医学 Q2 IMMUNOLOGY Pub Date : 2025-03-21 eCollection Date: 2025-01-01 DOI: 10.3389/fcimb.2025.1449873
Fang Yang, Jingtao Zhang, Junpu Zha, Guolei Zhang, Jia Li, Wei Du, Lin Liu, Jun Di

Background: Modic changes are caused by various factors, such as degenerative processes, inflammation, biomechanical, genetic, and metabolic factors, infection, and smoking. Bacteria have been identified in human intervertebral discs by 16S rRNA sequencing; however, the low microbial biomass in intervertebral disc tissue limits species-level analyses using this approach. In this study, we employed 2bRAD-M (2b Restriction Site Associated DNA sequencing for Microbiome), a new sequencing technology capable of accurately characterizing bacteria, fungi, and archaea in samples with low microbial biomass at species-level resolution.

Methods: We surveyed 20 intervertebral disc (IVD) samples, including 10 IVD samples with Modic changes and 10 herniated disc samples. 2bRAD-M was performed to explore whether microbial differences existed between Modic change and herniated disc samples.

Results: In total, 332 microbial species were identified, including 75 species shared between the two groups. Enrichment for Escherichia_coli, Cupriavidus_pauculus, and Bradyrhizobium_denitrificans was observed in the Modic change group, while Afipia_broomeae, Phyllobacterium_calauticae, Tardiphaga_sp002256345, Mesorhizobium_sp004136315, Afipia_sp000497575, Burkholderia_contaminans, and Afipia_sp017474385 were more abundant in the herniated disc group. Additionally, 19 discriminatory taxa were determined by linear discriminant analysis effect size (LEfSe). In a random forest model for partitioning the two groups, the species with the highest variable importance were Afipia_broomeae, Phyllobacterium_calauticae, and Escherichia_coli. Moreover, a newly constructed random forest model based on an optimal marker set consisting of eight highly abundant species successfully distinguished between the Modic change and herniated disc groups, with an accuracy of 81.0%. A functional annotation analysis showed that differentially abundant taxa between the Modic change and herniated disc groups could be assigned to 4093 COGs (Clusters of Orthologous Groups) and 342 related signaling pathways.

Conclusion: This study represents the first application of 2bRAD-M to Modic changes and disc herniation, revealing significant differences in microbial taxa between the two groups. These results suggest that microbial dysbiosis in the intervertebral disc is associated with Modic changes and provide candidate targets for further studies of the mechanisms underlying the development and progression of Modic changes.

{"title":"2bRAD-M reveals differences in microbial communities between Modic changes and disc herniation.","authors":"Fang Yang, Jingtao Zhang, Junpu Zha, Guolei Zhang, Jia Li, Wei Du, Lin Liu, Jun Di","doi":"10.3389/fcimb.2025.1449873","DOIUrl":"10.3389/fcimb.2025.1449873","url":null,"abstract":"<p><strong>Background: </strong>Modic changes are caused by various factors, such as degenerative processes, inflammation, biomechanical, genetic, and metabolic factors, infection, and smoking. Bacteria have been identified in human intervertebral discs by 16S rRNA sequencing; however, the low microbial biomass in intervertebral disc tissue limits species-level analyses using this approach. In this study, we employed 2bRAD-M (2b Restriction Site Associated DNA sequencing for Microbiome), a new sequencing technology capable of accurately characterizing bacteria, fungi, and archaea in samples with low microbial biomass at species-level resolution.</p><p><strong>Methods: </strong>We surveyed 20 intervertebral disc (IVD) samples, including 10 IVD samples with Modic changes and 10 herniated disc samples. 2bRAD-M was performed to explore whether microbial differences existed between Modic change and herniated disc samples.</p><p><strong>Results: </strong>In total, 332 microbial species were identified, including 75 species shared between the two groups. Enrichment for <i>Escherichia_coli</i>, <i>Cupriavidus_pauculus</i>, and <i>Bradyrhizobium_denitrificans</i> was observed in the Modic change group, while <i>Afipia_broomeae</i>, <i>Phyllobacterium_calauticae</i>, <i>Tardiphaga_sp002256345</i>, <i>Mesorhizobium_sp004136315</i>, <i>Afipia_sp000497575</i>, <i>Burkholderia_contaminans</i>, and <i>Afipia_sp017474385</i> were more abundant in the herniated disc group. Additionally, 19 discriminatory taxa were determined by linear discriminant analysis effect size (LEfSe). In a random forest model for partitioning the two groups, the species with the highest variable importance were <i>Afipia_broomeae</i>, <i>Phyllobacterium_calauticae</i>, and <i>Escherichia_coli</i>. Moreover, a newly constructed random forest model based on an optimal marker set consisting of eight highly abundant species successfully distinguished between the Modic change and herniated disc groups, with an accuracy of 81.0%. A functional annotation analysis showed that differentially abundant taxa between the Modic change and herniated disc groups could be assigned to 4093 COGs (Clusters of Orthologous Groups) and 342 related signaling pathways.</p><p><strong>Conclusion: </strong>This study represents the first application of 2bRAD-M to Modic changes and disc herniation, revealing significant differences in microbial taxa between the two groups. These results suggest that microbial dysbiosis in the intervertebral disc is associated with Modic changes and provide candidate targets for further studies of the mechanisms underlying the development and progression of Modic changes.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1449873"},"PeriodicalIF":4.6,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
A CRISPR/cas13a-assisted precise and portable test for Brucella nucleic acid detection.
IF 4.6 2区 医学 Q2 IMMUNOLOGY Pub Date : 2025-03-21 eCollection Date: 2025-01-01 DOI: 10.3389/fcimb.2025.1545953
Haiwen Liu, Ling Xu, Ying Xiu, Na Ta, Qingqing Xu, Yu Fan, Kun Li, Hongyan Zhao, Dongri Piao, Feng Ren, Hai Jiang

Introduction: Brucella infection in humans or animals can lead to brucellosis, which has the potential to significantly impact both the economy and public health. Currently, molecular biological methods for diagnosing brucellosis are either complex or have low sensitivity, and it is difficult to apply them in real-life settings in the field. Therefore, this study aims to establish a rapid and convenient nucleic acid-based molecular biology method for on-site rapid detection of Brucella and early clinical screening of brucellosis.

Methods: Based on the conserved sequence of the Brucella Bcsp31 gene, we designed CRISPR RNA (crRNA) and RAA primers. We developed a fluorescence detection method and a paper strip detection method by integrating RAA amplification with CRISPR/Cas13a detection. We applied these methods to analyze 100 samples of suspected brucellosis-infected milk, 123 samples of human whole blood, and 100 samples of sheep vaginal swabs in order to validate their practical utility.

Results: The RAA-CRISPR/Cas13a Brucella fluorescence detection method and the strip test method had detection limits of 100 copies/μL and 101 copies/μL, respectively, and both methods had a specificity of 100%. The positivity rate of the RAA-CRISPR/Cas13a fluorescence detection method for the milk, human whole blood, and sheep vaginal swab samples was 93% (93/100), 82.12% (101/123), and 91% (91/100), respectively; the strip test method, 87% (87/100), 64.23% (79/123), and 76% (76/100), respectively.

Conclusion: In this study, we have developed a RAA-CRISPR detection method based on the Brucella BCSP31 gene, with potential applications in the identification of Brucella nucleic acid and implications for clinical diagnosis of brucellosis.

{"title":"A CRISPR/cas13a-assisted precise and portable test for <i>Brucella</i> nucleic acid detection.","authors":"Haiwen Liu, Ling Xu, Ying Xiu, Na Ta, Qingqing Xu, Yu Fan, Kun Li, Hongyan Zhao, Dongri Piao, Feng Ren, Hai Jiang","doi":"10.3389/fcimb.2025.1545953","DOIUrl":"10.3389/fcimb.2025.1545953","url":null,"abstract":"<p><strong>Introduction: </strong><i>Brucella</i> infection in humans or animals can lead to brucellosis, which has the potential to significantly impact both the economy and public health. Currently, molecular biological methods for diagnosing brucellosis are either complex or have low sensitivity, and it is difficult to apply them in real-life settings in the field. Therefore, this study aims to establish a rapid and convenient nucleic acid-based molecular biology method for on-site rapid detection of <i>Brucella</i> and early clinical screening of brucellosis.</p><p><strong>Methods: </strong>Based on the conserved sequence of the <i>Brucella</i> Bcsp31 gene, we designed CRISPR RNA (crRNA) and RAA primers. We developed a fluorescence detection method and a paper strip detection method by integrating RAA amplification with CRISPR/Cas13a detection. We applied these methods to analyze 100 samples of suspected brucellosis-infected milk, 123 samples of human whole blood, and 100 samples of sheep vaginal swabs in order to validate their practical utility.</p><p><strong>Results: </strong>The RAA-CRISPR/Cas13a <i>Brucella</i> fluorescence detection method and the strip test method had detection limits of 10<sub>0</sub> copies/μL and 10<sub>1</sub> copies/μL, respectively, and both methods had a specificity of 100%. The positivity rate of the RAA-CRISPR/Cas13a fluorescence detection method for the milk, human whole blood, and sheep vaginal swab samples was 93% (93/100), 82.12% (101/123), and 91% (91/100), respectively; the strip test method, 87% (87/100), 64.23% (79/123), and 76% (76/100), respectively.</p><p><strong>Conclusion: </strong>In this study, we have developed a RAA-CRISPR detection method based on the <i>Brucella</i> BCSP31 gene, with potential applications in the identification of <i>Brucella</i> nucleic acid and implications for clinical diagnosis of brucellosis.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1545953"},"PeriodicalIF":4.6,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Global burden, subtype, risk factors and etiological analysis of enteric infections from 1990-2021: population based study.
IF 4.6 2区 医学 Q2 IMMUNOLOGY Pub Date : 2025-03-20 eCollection Date: 2025-01-01 DOI: 10.3389/fcimb.2025.1527765
Youao Zhang, Yuran Zhang, Zhifeng Chen, Zixuan Jia, Yulan Yu, Jieyan Wang, Hui Liang

Background: Enteric infections represent a prevalent global health issue and contribute significantly to the global disease burden. This study aims to investigate the patterns and trends of enteric infections from 1990 to 2021, providing valuable insights for health policy formulation, medical resource allocation, and the optimization of patient management plans.

Methods: We analyzed the Global Burden of Disease (GBD) 2021 for 21 regions and 204 countries to understand better the health burden using prevalence, incidence, mortality, and disability-adjusted life years (DALYs), subtype, risk factors, and etiology. We tested correlations with the Socio-demographic Index (SDI), and using decomposition analysis to dissect the reasons behind changes in epidemiological indicators of the disease.

Results: In 2021, the age-standardized rates of prevalence, incidence, deaths, and DALYs per 100,000 population for enteric infections were 879.58, 577.21, 17.83, and 1020.15, respectively. Compared to 1990, these rates exhibited -0.18, -0.12, -0.73, and -0.72 changes. Gender and age analyses revealed a higher burden among females, those under 15 years old, and the elderly. Regions with low SDI had higher epidemiological indicators. The burden of Typhoid fever declines in high-development regions. Unsafe water sources were identified as the primary risk factor globally in both 1990 and 2021. Rotavirus was the leading cause of deaths and DALYs.

Conclusion: This study highlights the complex epidemiological landscape of enteric infections, revealing variations in burden, risk factors, and etiological characteristics across age, gender, and geographical regions. It underscores the urgent need for healthcare professionals and policymakers to develop innovative prevention and healthcare strategies based on the current and evolving burden of enteric infections, to alleviate the global disease burden.

{"title":"Global burden, subtype, risk factors and etiological analysis of enteric infections from 1990-2021: population based study.","authors":"Youao Zhang, Yuran Zhang, Zhifeng Chen, Zixuan Jia, Yulan Yu, Jieyan Wang, Hui Liang","doi":"10.3389/fcimb.2025.1527765","DOIUrl":"10.3389/fcimb.2025.1527765","url":null,"abstract":"<p><strong>Background: </strong>Enteric infections represent a prevalent global health issue and contribute significantly to the global disease burden. This study aims to investigate the patterns and trends of enteric infections from 1990 to 2021, providing valuable insights for health policy formulation, medical resource allocation, and the optimization of patient management plans.</p><p><strong>Methods: </strong>We analyzed the Global Burden of Disease (GBD) 2021 for 21 regions and 204 countries to understand better the health burden using prevalence, incidence, mortality, and disability-adjusted life years (DALYs), subtype, risk factors, and etiology. We tested correlations with the Socio-demographic Index (SDI), and using decomposition analysis to dissect the reasons behind changes in epidemiological indicators of the disease.</p><p><strong>Results: </strong>In 2021, the age-standardized rates of prevalence, incidence, deaths, and DALYs per 100,000 population for enteric infections were 879.58, 577.21, 17.83, and 1020.15, respectively. Compared to 1990, these rates exhibited -0.18, -0.12, -0.73, and -0.72 changes. Gender and age analyses revealed a higher burden among females, those under 15 years old, and the elderly. Regions with low SDI had higher epidemiological indicators. The burden of Typhoid fever declines in high-development regions. Unsafe water sources were identified as the primary risk factor globally in both 1990 and 2021. Rotavirus was the leading cause of deaths and DALYs.</p><p><strong>Conclusion: </strong>This study highlights the complex epidemiological landscape of enteric infections, revealing variations in burden, risk factors, and etiological characteristics across age, gender, and geographical regions. It underscores the urgent need for healthcare professionals and policymakers to develop innovative prevention and healthcare strategies based on the current and evolving burden of enteric infections, to alleviate the global disease burden.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1527765"},"PeriodicalIF":4.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 plasmids in edema disease: Insights from whole-genome analysis of porcine O139:H1 Shiga toxin-producing Escherichia coli (STEC) strains.
IF 4.6 2区 医学 Q2 IMMUNOLOGY Pub Date : 2025-03-20 eCollection Date: 2025-01-01 DOI: 10.3389/fcimb.2025.1528408
Ali Nemati, Federica Gigliucci, Stefano Morabito, Mahdi Askari Badouei

This study investigates the plasmid sequences of porcine O139:H1 Shiga toxin-producing Escherichia coli (STEC) responsible for Edema Disease (ED). Whole-genome analysis reveals significant similarities between these strains and known plasmids, notably pW1316-2, which harbors key virulence genes like hemolysin (hlyA, hlyB) and adhesion factors (aidA-I, faeE). These genes contribute to the cytotoxicity and host colonization associated with ED. Additionally, similarities to plasmids from Shigella flexneri 2a highlight potential associations in virulence gene regulation, particularly via the Hha-H-NS complex. The identification of sequences resembling plasmid pB71 raises serious concerns about the emergence of highly pathogenic strains, as it includes tetracycline resistance genes (tetA, tetC, tetR). This research emphasizes the role of plasmid-like sequences in ED pathogenesis, indicating important implications for swine industry management and public health.

{"title":"Virulence plasmids in edema disease: Insights from whole-genome analysis of porcine O139:H1 Shiga toxin-producing <i>Escherichia coli</i> (STEC) strains.","authors":"Ali Nemati, Federica Gigliucci, Stefano Morabito, Mahdi Askari Badouei","doi":"10.3389/fcimb.2025.1528408","DOIUrl":"10.3389/fcimb.2025.1528408","url":null,"abstract":"<p><p>This study investigates the plasmid sequences of porcine O139:H1 Shiga toxin-producing <i>Escherichia coli</i> (STEC) responsible for Edema Disease (ED). Whole-genome analysis reveals significant similarities between these strains and known plasmids, notably pW1316-2, which harbors key virulence genes like hemolysin (<i>hlyA</i>, <i>hlyB</i>) and adhesion factors (<i>aidA-I</i>, <i>faeE</i>). These genes contribute to the cytotoxicity and host colonization associated with ED. Additionally, similarities to plasmids from <i>Shigella flexneri</i> 2a highlight potential associations in virulence gene regulation, particularly via the <i>Hha-H-NS</i> complex. The identification of sequences resembling plasmid pB71 raises serious concerns about the emergence of highly pathogenic strains, as it includes tetracycline resistance genes (<i>tetA</i>, <i>tetC</i>, <i>tetR</i>). This research emphasizes the role of plasmid-like sequences in ED pathogenesis, indicating important implications for swine industry management and public health.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1528408"},"PeriodicalIF":4.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Bacteriocin KvarM versus conventional antibiotics: comparative effectiveness in treating Klebsiella pneumoniae infections in murine intestinal models.
IF 4.6 2区 医学 Q2 IMMUNOLOGY Pub Date : 2025-03-20 eCollection Date: 2025-01-01 DOI: 10.3389/fcimb.2025.1559865
Indre Karaliute, Deimante Tilinde, Rima Ramonaite, Rokas Lukosevicius, Darja Nikitina, Jurga Bernatoniene, Irma Kuliaviene, Irena Valantiene, Dalius Petrauskas, Vilma Zigmantaite, Audrius Misiunas, Erna Denkovskiene, Ausra Razanskiene, Yuri Gleba, Juozas Kupcinskas, Jurgita Skieceviciene

Introduction: The rapid emergence of multidrug-resistant bacterial species poses a critical threat by reducing the efficacy of antibiotics and complicating infection treatment. Bacteriocins, such as klebicin KvarM, have emerged as promising alternatives to traditional antibiotics due to their targeted antimicrobial activity. In this study, we evaluated the therapeutic potential of Eudragit-coated klebicin KvarM in a mouse model of Klebsiella pneumoniae intestinal colonization, assessing both its antimicrobial effectiveness and impact on commensal gut microbiota.

Methods: Antimicrobial activity of KvarM in comparison to conventional antibiotic therapy with ciprofloxacin was tested in murine models for K. pneumoniae gastrointestinal (GI) tract infection. The haemolysin gene (khe) was chosen as the qualitative marker for Klebsiella genus identification, and 16S rRNA gene sequencing of V1-V2 hypervariable region was performed for analyses of gut microbiota.

Results: Our results demonstrated that KvarM was highly effective in reducing K. pneumoniae colonization, showing the same efficacy as ciprofloxacin. Following K. pneumoniae inoculation, administration of KvarM resulted in a significant reduction in bacterial load indicating a 99% effectiveness. Furthermore, microbiome analysis of the gut microbiota revealed that KvarM therapy showed no significant changes in microbial composition compared with commensal microbiota composition, whereas administration of ciprofloxacin led to a significant decrease in microbial diversity.

Discussion: These findings demonstrate that klebicin KvarM therapy is highly effective for treating intestinal K. pneumoniae infections and it does not affect the integrity of the gut microbiota.

导言:耐多药细菌的迅速出现降低了抗生素的疗效,并使感染治疗复杂化,构成了严重威胁。克利比星 KvarM 等细菌素因其靶向抗菌活性,已成为传统抗生素的有前途的替代品。在本研究中,我们在肺炎克雷伯氏菌肠道定植小鼠模型中评估了Eudragit包被的克雷伯菌素KvarM的治疗潜力,同时评估了其抗菌效果和对肠道共生微生物群的影响:方法:在肺炎克雷伯菌胃肠道(GI)感染小鼠模型中测试了 KvarM 与环丙沙星传统抗生素疗法的抗菌活性。选择溶血素基因(khe)作为鉴定克雷伯氏菌属的定性标记,并对 V1-V2 超变区的 16S rRNA 基因进行测序,以分析肠道微生物群:结果:我们的研究结果表明,KvarM 能有效减少肺炎克雷伯菌的定植,其疗效与环丙沙星相同。肺炎双球菌接种后,服用 KvarM 能显著减少细菌量,有效率达 99%。此外,对肠道微生物群进行的微生物组分析表明,与共生微生物群组成相比,KvarM疗法没有导致微生物组成发生显著变化,而服用环丙沙星则导致微生物多样性显著减少:这些研究结果表明,克雷霉素 KvarM疗法对治疗肠道肺炎克氏菌感染非常有效,而且不会影响肠道微生物群的完整性。
{"title":"Bacteriocin KvarM versus conventional antibiotics: comparative effectiveness in treating <i>Klebsiella pneumoniae</i> infections in murine intestinal models.","authors":"Indre Karaliute, Deimante Tilinde, Rima Ramonaite, Rokas Lukosevicius, Darja Nikitina, Jurga Bernatoniene, Irma Kuliaviene, Irena Valantiene, Dalius Petrauskas, Vilma Zigmantaite, Audrius Misiunas, Erna Denkovskiene, Ausra Razanskiene, Yuri Gleba, Juozas Kupcinskas, Jurgita Skieceviciene","doi":"10.3389/fcimb.2025.1559865","DOIUrl":"10.3389/fcimb.2025.1559865","url":null,"abstract":"<p><strong>Introduction: </strong>The rapid emergence of multidrug-resistant bacterial species poses a critical threat by reducing the efficacy of antibiotics and complicating infection treatment. Bacteriocins, such as klebicin KvarM, have emerged as promising alternatives to traditional antibiotics due to their targeted antimicrobial activity. In this study, we evaluated the therapeutic potential of Eudragit-coated klebicin KvarM in a mouse model of <i>Klebsiella pneumoniae</i> intestinal colonization, assessing both its antimicrobial effectiveness and impact on commensal gut microbiota.</p><p><strong>Methods: </strong>Antimicrobial activity of KvarM in comparison to conventional antibiotic therapy with ciprofloxacin was tested in murine models for <i>K. pneumoniae</i> gastrointestinal (GI) tract infection. The haemolysin gene (<i>khe</i>) was chosen as the qualitative marker for <i>Klebsiella</i> genus identification, and 16S rRNA gene sequencing of V1-V2 hypervariable region was performed for analyses of gut microbiota.</p><p><strong>Results: </strong>Our results demonstrated that KvarM was highly effective in reducing <i>K. pneumoniae</i> colonization, showing the same efficacy as ciprofloxacin. Following <i>K. pneumoniae</i> inoculation, administration of KvarM resulted in a significant reduction in bacterial load indicating a 99% effectiveness. Furthermore, microbiome analysis of the gut microbiota revealed that KvarM therapy showed no significant changes in microbial composition compared with commensal microbiota composition, whereas administration of ciprofloxacin led to a significant decrease in microbial diversity.</p><p><strong>Discussion: </strong>These findings demonstrate that klebicin KvarM therapy is highly effective for treating intestinal <i>K. pneumoniae</i> infections and it does not affect the integrity of the gut microbiota.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1559865"},"PeriodicalIF":4.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
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Frontiers in Cellular and Infection Microbiology
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