Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, with great clinical heterogeneity, high morbidity, and high mortality. At the same time, there are many kinds of infection sources, the pathophysiology is very complex, and the pathogenesis has not been fully elucidated. An ideal animal model of sepsis can accurately simulate clinical sepsis and promote the development of sepsis-related pathogenesis, treatment methods, and prognosis. The existing sepsis model still uses the previous Sepsis 2.0 modelling standard, which has some problems, such as many kinds of infection sources, poor repeatability, inability to take into account single-factor studies, and large differences from clinical sepsis patients. To solve these problems, this study established a new animal model of sepsis. The model uses intravenous tail injection of a single bacterial strain, simplifying the complexity of multibacterial infection, and effectively solving the above problems.
{"title":"Simulating the clinical manifestations and disease progression of human sepsis: A monobacterial injection approach for animal modeling.","authors":"Xuanwen Ru, Simiao Chen, Danlei Chen, Qingyi Shao, Wenxia Shao, Qing Ye","doi":"10.1080/21505594.2024.2395835","DOIUrl":"10.1080/21505594.2024.2395835","url":null,"abstract":"<p><p>Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, with great clinical heterogeneity, high morbidity, and high mortality. At the same time, there are many kinds of infection sources, the pathophysiology is very complex, and the pathogenesis has not been fully elucidated. An ideal animal model of sepsis can accurately simulate clinical sepsis and promote the development of sepsis-related pathogenesis, treatment methods, and prognosis. The existing sepsis model still uses the previous Sepsis 2.0 modelling standard, which has some problems, such as many kinds of infection sources, poor repeatability, inability to take into account single-factor studies, and large differences from clinical sepsis patients. To solve these problems, this study established a new animal model of sepsis. The model uses intravenous tail injection of a single bacterial strain, simplifying the complexity of multibacterial infection, and effectively solving the above problems.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"15 1","pages":"2395835"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11370922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142112634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-09-17DOI: 10.1080/21505594.2024.2399983
Juan Guo, Qingqiang Xu, Yilin Zhong, Yubin Su
Bacterial resistance poses a significant threat to both human and animal health. N-acetylcysteine (NAC), which is used as an anti-inflammatory, has been shown to have distinct and contrasting impacts on bacterial resistance. However, the precise mechanism underlying the relationship between NAC and bacterial resistance remains unclear and requires further investigation. In this study, we study the effect of NAC on bacterial resistance and the underlying mechanisms. Specifically, we examine the effects of NAC on Edwardsiella tarda ATCC15947, a pathogen that exhibits resistance to many antibiotics. We find that NAC can promote resistance of E. tarda to many antibiotics, such as doxycycline, resulting in an increase in the bacterial survival rate. Through proteomic analysis, we demonstrate that NAC activates the amino acid metabolism pathway in E. tarda, leading to elevated intracellular glutathione (GSH) levels and reduced reactive oxygen species (ROS). Additionally, NAC reduces antibiotic influx while enhancing efflux, thus maintaining low intracellular antibiotic concentrations. We also propose that NAC promotes protein aggregation, thus contributing to antibiotic resistance. Our study describes the mechanism underlying E. tarda resistance to doxycycline and cautions against the indiscriminate use of metabolite adjuvants.
{"title":"N-acetylcysteine promotes doxycycline resistance in the bacterial pathogen <i>Edwardsiella tarda</i>.","authors":"Juan Guo, Qingqiang Xu, Yilin Zhong, Yubin Su","doi":"10.1080/21505594.2024.2399983","DOIUrl":"10.1080/21505594.2024.2399983","url":null,"abstract":"<p><p>Bacterial resistance poses a significant threat to both human and animal health. N-acetylcysteine (NAC), which is used as an anti-inflammatory, has been shown to have distinct and contrasting impacts on bacterial resistance. However, the precise mechanism underlying the relationship between NAC and bacterial resistance remains unclear and requires further investigation. In this study, we study the effect of NAC on bacterial resistance and the underlying mechanisms. Specifically, we examine the effects of NAC on <i>Edwardsiella tarda</i> ATCC15947, a pathogen that exhibits resistance to many antibiotics. We find that NAC can promote resistance of <i>E. tarda</i> to many antibiotics, such as doxycycline, resulting in an increase in the bacterial survival rate. Through proteomic analysis, we demonstrate that NAC activates the amino acid metabolism pathway in <i>E. tarda</i>, leading to elevated intracellular glutathione (GSH) levels and reduced reactive oxygen species (ROS). Additionally, NAC reduces antibiotic influx while enhancing efflux, thus maintaining low intracellular antibiotic concentrations. We also propose that NAC promotes protein aggregation, thus contributing to antibiotic resistance. Our study describes the mechanism underlying <i>E. tarda</i> resistance to doxycycline and cautions against the indiscriminate use of metabolite adjuvants.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":" ","pages":"2399983"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11409502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: The COVID-19 pandemic has led to millions of fatalities globally. Kidney transplant (KT) patients, given their comorbidities and under immunosuppressant drugs, are identified as a high-risk group. Though vaccination remains pivotal for pandemic control, some studies indicate that KT exhibits diminished immune reactions to SARS-CoV-2 vaccines. Therefore, evaluating the vaccine responses in KT, especially the humoral responses against emergent variants is crucial.Methods: We developed a multiplexed SARS-CoV-2 variant protein microarray, incorporating the extracellular domain (ECD) and the receptor binding domain (RBD) of the spike proteins from the variants. This was employed to investigate the collective humoral responses after administering two doses of mRNA-1273 and AZD1222 vaccines in KT under immunosuppressive drugs and in healthy controls.Results: After two doses of either mRNA-1273 or AZD1222, the KT generally showed lower surrogate neutralizing and total antibodies against spike ECD in multiple variants compared to healthy controls. Although two doses of mRNA-1273 induced 1.5-2 fold more surrogate neutralizing and total antibodies than AZD1222 in healthy controls, the KT subjects with two doses of mRNA-1273 generally exhibited higher surrogate neutralizing but similar total antibodies against spike ECD in multiple variants. There were moderate to high correlations between the surrogate neutralizing and total antibodies against spike ECDs.Conclusion: This study offers pivotal insights into the relative vulnerability of KT concerning humoral immunity and the evolving mutations of SARS-CoV-2. Such findings are useful for evaluating vaccine responses and recommending vaccine episodes for KT.
{"title":"Humoral responses to multiple SARS-CoV-2 variants after two doses of vaccine in kidney transplant patients.","authors":"Pin-Xian Du, Shen-Shin Chang, Tzong-Shiann Ho, Hsi-Chang Shih, Pei-Shan Tsai, Guan-Da Syu","doi":"10.1080/21505594.2024.2351266","DOIUrl":"10.1080/21505594.2024.2351266","url":null,"abstract":"<p><p><b>Background:</b> The COVID-19 pandemic has led to millions of fatalities globally. Kidney transplant (KT) patients, given their comorbidities and under immunosuppressant drugs, are identified as a high-risk group. Though vaccination remains pivotal for pandemic control, some studies indicate that KT exhibits diminished immune reactions to SARS-CoV-2 vaccines. Therefore, evaluating the vaccine responses in KT, especially the humoral responses against emergent variants is crucial.<b>Methods:</b> We developed a multiplexed SARS-CoV-2 variant protein microarray, incorporating the extracellular domain (ECD) and the receptor binding domain (RBD) of the spike proteins from the variants. This was employed to investigate the collective humoral responses after administering two doses of mRNA-1273 and AZD1222 vaccines in KT under immunosuppressive drugs and in healthy controls.<b>Results:</b> After two doses of either mRNA-1273 or AZD1222, the KT generally showed lower surrogate neutralizing and total antibodies against spike ECD in multiple variants compared to healthy controls. Although two doses of mRNA-1273 induced 1.5-2 fold more surrogate neutralizing and total antibodies than AZD1222 in healthy controls, the KT subjects with two doses of mRNA-1273 generally exhibited higher surrogate neutralizing but similar total antibodies against spike ECD in multiple variants. There were moderate to high correlations between the surrogate neutralizing and total antibodies against spike ECDs.<b>Conclusion:</b> This study offers pivotal insights into the relative vulnerability of KT concerning humoral immunity and the evolving mutations of SARS-CoV-2. Such findings are useful for evaluating vaccine responses and recommending vaccine episodes for KT.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"15 1","pages":"2351266"},"PeriodicalIF":5.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11085947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140877505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-05-09DOI: 10.1080/21505594.2024.2350904
Xinhao Du, Zhenzhen Tang, Li Yan, Ling Zhang, Qiao Zheng, Xianghao Zeng, Qing Hu, Qian Tian, Lanfan Liang, Xinyu Zhao, Jun Li, Ming Zhao, Xiangsheng Fu
Fusobacterium nucleatum (F. nucleatum) is closely correlated with tumorigenesis in colorectal cancer (CRC). We aimed to investigate the effects of host norepinephrine on the carcinogenicity of F. nucleatum in CRC and reveal the underlying mechanism. The results revealed that both norepinephrine and bacterial quorum sensing (QS) molecule auto-inducer-2 (AI-2) were positively associated with the progression of F. nucleatum related CRC (p < 0.01). In vitro studies, norepinephrine induced upregulation of QS-associated genes and promoted the virulence and proliferation of F. nucleatum. Moreover, chronic stress significantly increased the colon tumour burden of ApcMin/+ mice infected with F. nucleatum (p < 0.01), which was decreased by a catecholamine inhibitor (p < 0.001). Our findings suggest that stress-induced norepinephrine may promote the progression of F. nucleatum related CRC via bacterial QS signalling. These preliminary data provide a novel strategy for the management of pathogenic bacteria by targeting host hormones-bacterial QS inter-kingdom signalling.
核叉杆菌(F. nucleatum)与结直肠癌(CRC)的肿瘤发生密切相关。我们旨在研究宿主去甲肾上腺素对核分枝杆菌在 CRC 中致癌性的影响,并揭示其潜在机制。结果发现,去甲肾上腺素和细菌法定量传感(QS)分子自动诱导因子-2(AI-2)均与F. nucleatum相关CRC的进展呈正相关(p 在体外研究中,去甲肾上腺素诱导QS相关基因上调,促进F. nucleatum的毒力和增殖。此外,慢性应激通过细菌 QS 信号传导,明显增加了感染 F. nucleatum 的 ApcMin/+ 小鼠的结肠肿瘤负荷(p p F. nucleatum related CRC)。这些初步数据为通过靶向宿主激素-细菌 QS 部门间信号来管理病原菌提供了一种新策略。
{"title":"Norepinephrine may promote the progression of <i>Fusobacterium nucleatum</i> related colorectal cancer via quorum sensing signalling.","authors":"Xinhao Du, Zhenzhen Tang, Li Yan, Ling Zhang, Qiao Zheng, Xianghao Zeng, Qing Hu, Qian Tian, Lanfan Liang, Xinyu Zhao, Jun Li, Ming Zhao, Xiangsheng Fu","doi":"10.1080/21505594.2024.2350904","DOIUrl":"10.1080/21505594.2024.2350904","url":null,"abstract":"<p><p><i>Fusobacterium nucleatum (F. nucleatum)</i> is closely correlated with tumorigenesis in colorectal cancer (CRC). We aimed to investigate the effects of host norepinephrine on the carcinogenicity of <i>F. nucleatum</i> in CRC and reveal the underlying mechanism. The results revealed that both norepinephrine and bacterial quorum sensing (QS) molecule auto-inducer-2 (AI-2) were positively associated with the progression of <i>F. nucleatum</i> related CRC (<i>p</i> < 0.01). <i>In vitro</i> studies, norepinephrine induced upregulation of QS-associated genes and promoted the virulence and proliferation of <i>F. nucleatum</i>. Moreover, chronic stress significantly increased the colon tumour burden of Apc<sup>Min/+</sup> mice infected with <i>F. nucleatum</i> (<i>p</i> < 0.01), which was decreased by a catecholamine inhibitor (<i>p</i> < 0.001). Our findings suggest that stress-induced norepinephrine may promote the progression of <i>F. nucleatum</i> related CRC via bacterial QS signalling. These preliminary data provide a novel strategy for the management of pathogenic bacteria by targeting host hormones-bacterial QS inter-kingdom signalling.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"15 1","pages":"2350904"},"PeriodicalIF":5.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11085999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140899349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-07-09DOI: 10.1080/21505594.2024.2375549
Xiaofei Ji, Qianwen Wu, Xinying Cao, Shuzhen Liu, Jianhui Zhang, Si Chen, Jiangfan Shan, Ying Zhang, Boqing Li, Huilin Zhao
CagA is a significant oncogenic factor injected into host cells by Helicobacter pylori, which is divided into two subtypes: East Asian type (CagAE), characterized by the EPIYA-D motif, and western type (CagAW), harboring the EPIYA-C motif. CagAE has been reported to have higher carcinogenicity than CagAW, although the underlying reason is not fully understood. SHIP2 is an intracellular phosphatase that can be recruited by CagA to perturb the homeostasis of intracellular signaling pathways. In this study, we found that SHIP2 contributes to the higher oncogenicity of CagAE. Co-Immunoprecipitation and Pull-down assays showed that CagAE bind more SHIP2 than CagAW. Immunofluorescence staining showed that a higher amount of SHIP2 recruited by CagAE to the plasma membrane catalyzes the conversion of PI(3,4,5)P3 into PI(3,4)P2. This alteration causes higher activation of Akt signaling, which results in enhanced IL-8 secretion, migration, and invasion of the infected cells. SPR analysis showed that this stronger interaction between CagAE and SHIP2 stems from the higher affinity between the EPIYA-D motif of CagAE and the SH2 domain of SHIP2. Structural analysis revealed the crucial role of the Phe residue at the Y + 5 position in EPIYA-D. After mutating Phe of CagAE into Asp (the corresponding residue in the EPIYA-C motif) or Ala, the activation of downstream Akt signaling was reduced and the malignant transformation of infected cells was alleviated. These findings revealed that CagAE hijacks SHIP2 through its EPIYA-D motif to enhance its carcinogenicity, which provides a better understanding of the higher oncogenic risk of H. pylori CagAE.
{"title":"<i>Helicobacter pylori</i> East Asian type CagA hijacks more SHIP2 by its EPIYA-D motif to potentiate the oncogenicity.","authors":"Xiaofei Ji, Qianwen Wu, Xinying Cao, Shuzhen Liu, Jianhui Zhang, Si Chen, Jiangfan Shan, Ying Zhang, Boqing Li, Huilin Zhao","doi":"10.1080/21505594.2024.2375549","DOIUrl":"10.1080/21505594.2024.2375549","url":null,"abstract":"<p><p>CagA is a significant oncogenic factor injected into host cells by <i>Helicobacter pylori</i>, which is divided into two subtypes: East Asian type (CagA<sup>E</sup>), characterized by the EPIYA-D motif, and western type (CagA<sup>W</sup>), harboring the EPIYA-C motif. CagA<sup>E</sup> has been reported to have higher carcinogenicity than CagA<sup>W</sup>, although the underlying reason is not fully understood. SHIP2 is an intracellular phosphatase that can be recruited by CagA to perturb the homeostasis of intracellular signaling pathways. In this study, we found that SHIP2 contributes to the higher oncogenicity of CagA<sup>E</sup>. Co-Immunoprecipitation and Pull-down assays showed that CagA<sup>E</sup> bind more SHIP2 than CagA<sup>W</sup>. Immunofluorescence staining showed that a higher amount of SHIP2 recruited by CagA<sup>E</sup> to the plasma membrane catalyzes the conversion of PI(3,4,5)P<sub>3</sub> into PI(3,4)P<sub>2</sub>. This alteration causes higher activation of Akt signaling, which results in enhanced IL-8 secretion, migration, and invasion of the infected cells. SPR analysis showed that this stronger interaction between CagA<sup>E</sup> and SHIP2 stems from the higher affinity between the EPIYA-D motif of CagA<sup>E</sup> and the SH2 domain of SHIP2. Structural analysis revealed the crucial role of the Phe residue at the Y + 5 position in EPIYA-D. After mutating Phe of CagA<sup>E</sup> into Asp (the corresponding residue in the EPIYA-C motif) or Ala, the activation of downstream Akt signaling was reduced and the malignant transformation of infected cells was alleviated. These findings revealed that CagA<sup>E</sup> hijacks SHIP2 through its EPIYA-D motif to enhance its carcinogenicity, which provides a better understanding of the higher oncogenic risk of <i>H. pylori</i> CagA<sup>E</sup>.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"15 1","pages":"2375549"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11238919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141564525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Porcine reproductive and respiratory syndrome virus (PRRSV) causes a highly contagious disease that threatens the global swine industry. Recent studies have focused on the damage that PRRSV causes to the reproductive system of male pigs, although pathological research is lacking. Therefore, we examined the pathogenic mechanisms in male piglets infected with PRRSV. Gross and histopathological changes indicated that PRRSV affected the entire reproductive system, as confirmed via immunohistochemical analysis. PRRSV infected Sertoli cells and spermatogonia. To test the new hypothesis that PRRSV infection in piglets impairs blood - testis barrier (BTB) development, we investigated the pathology of PRRSV damage in the BTB. PRRSV infection significantly decreased the quantity and proliferative capacity of Sertoli cells constituting the BTB. Zonula occludens-1 and β-catenin were downregulated in cell - cell junctions. Transcriptome analysis revealed that several crucial genes and signalling pathways involved in the growth and development of Leydig cells, Sertoli cells, and tight junctions in the testes were downregulated. Apoptosis, necroptosis, inflammatory, and oxidative stress-related pathways were activated, whereas hormone secretion-related pathways were inhibited. Many Sertoli cells and spermatogonia underwent apoptosis during early differentiation. Infected piglets exhibited disrupted androgen secretion, leading to significantly reduced testosterone and anti-Müllerian hormone levels. A cytokine storm occurred, notably upregulating cytokines such as tumour necrosis factor-α and interleukin-6. Markers of oxidative-stress damage (i.e. H2O2, malondialdehyde, and glutathione) were upregulated, whereas antioxidant-enzyme activities (i.e. superoxide dismutase, total antioxidant capacity, and catalase) were downregulated. Our results demonstrated that PRRSV infected multiple organs in the male reproductive system, which impaired growth in the BTB.
{"title":"Porcine reproductive and respiratory syndrome virus infects the reproductive system of male piglets and impairs development of the blood-testis barrier.","authors":"Bingzhou Huang, Fengqin Li, Dong You, Lishuang Deng, Tong Xu, Siyuan Lai, Yanru Ai, Jianbo Huang, Yuancheng Zhou, Liangpeng Ge, Xiu Zeng, Zhiwen Xu, Ling Zhu","doi":"10.1080/21505594.2024.2384564","DOIUrl":"10.1080/21505594.2024.2384564","url":null,"abstract":"<p><p>Porcine reproductive and respiratory syndrome virus (PRRSV) causes a highly contagious disease that threatens the global swine industry. Recent studies have focused on the damage that PRRSV causes to the reproductive system of male pigs, although pathological research is lacking. Therefore, we examined the pathogenic mechanisms in male piglets infected with PRRSV. Gross and histopathological changes indicated that PRRSV affected the entire reproductive system, as confirmed via immunohistochemical analysis. PRRSV infected Sertoli cells and spermatogonia. To test the new hypothesis that PRRSV infection in piglets impairs blood - testis barrier (BTB) development, we investigated the pathology of PRRSV damage in the BTB. PRRSV infection significantly decreased the quantity and proliferative capacity of Sertoli cells constituting the BTB. Zonula occludens-1 and β-catenin were downregulated in cell - cell junctions. Transcriptome analysis revealed that several crucial genes and signalling pathways involved in the growth and development of Leydig cells, Sertoli cells, and tight junctions in the testes were downregulated. Apoptosis, necroptosis, inflammatory, and oxidative stress-related pathways were activated, whereas hormone secretion-related pathways were inhibited. Many Sertoli cells and spermatogonia underwent apoptosis during early differentiation. Infected piglets exhibited disrupted androgen secretion, leading to significantly reduced testosterone and anti-Müllerian hormone levels. A cytokine storm occurred, notably upregulating cytokines such as tumour necrosis factor-α and interleukin-6. Markers of oxidative-stress damage (i.e. H<sub>2</sub>O<sub>2</sub>, malondialdehyde, and glutathione) were upregulated, whereas antioxidant-enzyme activities (i.e. superoxide dismutase, total antioxidant capacity, and catalase) were downregulated. Our results demonstrated that PRRSV infected multiple organs in the male reproductive system, which impaired growth in the BTB.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"15 1","pages":"2384564"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11290757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141789203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-09-09DOI: 10.1080/21505594.2024.2399217
Donghao Li, Zongwei Li, Lei Wang, Yan Zhang, Shoubin Ning
Fusobacterium nucleatum (F. nucleatum), an anaerobic resident of the oral cavity, is increasingly recognized as a contributing factor to ulcerative colitis (UC). The adhesive properties of F. nucleatum are mediated by its key virulence protein, FadA adhesin. However, further investigations are needed to understand the pathogenic mechanisms of this oral pathogen in UC. The present study aimed to explore the role of the FadA adhesin in the colonization and invasion of oral F. nucleatum in dextran sulphate sodium (DSS)-induced colitis mice via molecular techniques. In this study, we found that oral inoculation of F. nucleatum strain carrying the FadA adhesin further exacerbated DSS-induced colitis, leading to elevated alveolar bone loss, disease severity, and mortality. Additionally, CDH1 gene knockout mice treated with DSS presented increases in body weight and alveolar bone density, as well as a reduction in disease severity. Furthermore, FadA adhesin adhered to its mucosal receptor E-cadherin, leading to the phosphorylation of β-catenin and the degradation of IκBα, the activation of the NF-κB signalling pathway and the upregulation of downstream cytokines. In conclusion, this research revealed that oral inoculation with F. nucleatum facilitates experimental colitis via the secretion of the virulence adhesin FadA. Targeting the oral pathogen F. nucleatum and its virulence factor FadA may represent a promising therapeutic approach for a portion of UC patients.
{"title":"Oral inoculation of <i>Fusobacterium nucleatum</i> exacerbates ulcerative colitis via the secretion of virulence adhesin FadA.","authors":"Donghao Li, Zongwei Li, Lei Wang, Yan Zhang, Shoubin Ning","doi":"10.1080/21505594.2024.2399217","DOIUrl":"10.1080/21505594.2024.2399217","url":null,"abstract":"<p><p><i>Fusobacterium nucleatum</i> (<i>F. nucleatum</i>), an anaerobic resident of the oral cavity, is increasingly recognized as a contributing factor to ulcerative colitis (UC). The adhesive properties of <i>F. nucleatum</i> are mediated by its key virulence protein, FadA adhesin. However, further investigations are needed to understand the pathogenic mechanisms of this oral pathogen in UC. The present study aimed to explore the role of the FadA adhesin in the colonization and invasion of oral <i>F. nucleatum</i> in dextran sulphate sodium (DSS)-induced colitis mice via molecular techniques. In this study, we found that oral inoculation of <i>F. nucleatum</i> strain carrying the FadA adhesin further exacerbated DSS-induced colitis, leading to elevated alveolar bone loss, disease severity, and mortality. Additionally, CDH1 gene knockout mice treated with DSS presented increases in body weight and alveolar bone density, as well as a reduction in disease severity. Furthermore, FadA adhesin adhered to its mucosal receptor E-cadherin, leading to the phosphorylation of β-catenin and the degradation of IκBα, the activation of the NF-κB signalling pathway and the upregulation of downstream cytokines. In conclusion, this research revealed that oral inoculation with <i>F. nucleatum</i> facilitates experimental colitis via the secretion of the virulence adhesin FadA. Targeting the oral pathogen <i>F. nucleatum</i> and its virulence factor FadA may represent a promising therapeutic approach for a portion of UC patients.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":" ","pages":"2399217"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11385161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142112635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Well-intestinal health is crucial for better growth performance in pigs. Type 3 immunity, which is one of the three types of immune responses in mammals, plays a vital role in maintaining intestinal homoeostasis. Therefore, we initially introduce the type 3 immune cells in the intestine of pigs, including their distribution, development, and function. We then discuss the type 3 immune response under infection, encompassing bacterial, fungal, and viral infections. It also covers two major stresses in pigs: heat stress and weaning stress. Lastly, we discuss the effects of various nutrients and feed additives on the regulation of the type 3 immune response in pigs under infection. This review aims to contribute to the understanding of the interaction between infection and type 3 immunity in pigs and to illustrate how various nutrients modulate the type 3 immune response in pigs under diverse infections.
{"title":"The formidable guardian: Type 3 immunity in the intestine of pigs.","authors":"Zhipeng Yang, Dou Zhang, Zhoudan Jiang, Jian Peng, Hongkui Wei","doi":"10.1080/21505594.2024.2424325","DOIUrl":"10.1080/21505594.2024.2424325","url":null,"abstract":"<p><p>Well-intestinal health is crucial for better growth performance in pigs. Type 3 immunity, which is one of the three types of immune responses in mammals, plays a vital role in maintaining intestinal homoeostasis. Therefore, we initially introduce the type 3 immune cells in the intestine of pigs, including their distribution, development, and function. We then discuss the type 3 immune response under infection, encompassing bacterial, fungal, and viral infections. It also covers two major stresses in pigs: heat stress and weaning stress. Lastly, we discuss the effects of various nutrients and feed additives on the regulation of the type 3 immune response in pigs under infection. This review aims to contribute to the understanding of the interaction between infection and type 3 immunity in pigs and to illustrate how various nutrients modulate the type 3 immune response in pigs under diverse infections.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":" ","pages":"2424325"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11552283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-05-02DOI: 10.1080/21505594.2024.2348251
Jiankang Zhao, Danni Pu, Ziyao Li, Yulin Zhang, Xinmeng Liu, Xianxia Zhuo, Binghuai Lu, Bin Cao
Objectives: This study aimed at revealing the underlying mechanisms of the loss and gain of ceftazidime-avibactam susceptibility in a non-carbapenemase-producing hypervirulent Klebsiella pneumoniae (hvKp).
Methods: Here we longitudinally recovered 3 non-carbapenemase-producing K1-ST23 hvKp strains at a one-month interval (KP29105, KP29499 and KP30086) from an elderly male. Antimicrobial susceptibility testing, whole genome sequencing, transcriptomic sequencing, gene cloning, plasmid conjugation, quantitative real-time PCR (qRT-PCR), and SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis) were conducted.
Results: Among the 3 hvKp strains, KP29105 was resistant to the third- and fourth-generation cephalosporins, KP29499 acquired resistance to both ceftazidime-avibactam and carbapenems, while KP30086 restored its susceptibility to ceftazidime-avibactam, imipenem and meropenem but retained low-level resistance to ertapenem. KP29105 and KP29499 carried plasmid-encoded genes blaCTX-M-15 and blaCTX-M-71, respectively, but KP30086 lost both. Cloning of gene blaCTX-M-71 and conjugation experiment of blaCTX-M-71-carrying plasmid showed that the transformant and transconjugant were susceptible to ceftazidime-avibactam but had a more than 8-fold increase in MICs. Supplementation with an outer membrane permeabilizer could reduce the MIC of ceftazidime-avibactam by 32 folds, indicating that porins play a key role in ceftazidime-avibactam resistance. The OmpK35 of the 3 isolates was not expressed, and the OmpK36 of KP29499 and KP30086 had a novel amino acid substitution (L359R). SDS-PAGE and qRT-PCR showed that the expression of porin OmpK36 of KP29499 and KP30086 was significantly down-regulated compared with KP29105.
Conclusions: In summary, we reported the rare ceftazidime-avibactam resistance in a non-carbapenemase-producing hvKp strain. Resistance plasmid carrying blaCTX-M-71 and mutated OmpK36 had a synergetic effect on the resistance.
{"title":"Loss and gain of ceftazidime-avibactam susceptibility in a non-carbapenemase-producing K1-ST23 hypervirulent <i>Klebsiella pneumoniae</i>.","authors":"Jiankang Zhao, Danni Pu, Ziyao Li, Yulin Zhang, Xinmeng Liu, Xianxia Zhuo, Binghuai Lu, Bin Cao","doi":"10.1080/21505594.2024.2348251","DOIUrl":"10.1080/21505594.2024.2348251","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed at revealing the underlying mechanisms of the loss and gain of ceftazidime-avibactam susceptibility in a non-carbapenemase-producing hypervirulent <i>Klebsiella pneumoniae</i> (hvKp).</p><p><strong>Methods: </strong>Here we longitudinally recovered 3 non-carbapenemase-producing K1-ST23 hvKp strains at a one-month interval (KP29105, KP29499 and KP30086) from an elderly male. Antimicrobial susceptibility testing, whole genome sequencing, transcriptomic sequencing, gene cloning, plasmid conjugation, quantitative real-time PCR (qRT-PCR), and SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis) were conducted.</p><p><strong>Results: </strong>Among the 3 hvKp strains, KP29105 was resistant to the third- and fourth-generation cephalosporins, KP29499 acquired resistance to both ceftazidime-avibactam and carbapenems, while KP30086 restored its susceptibility to ceftazidime-avibactam, imipenem and meropenem but retained low-level resistance to ertapenem. KP29105 and KP29499 carried plasmid-encoded genes <i>bla</i><sub>CTX-M-15</sub> and <i>bla</i><sub>CTX-M-71</sub>, respectively, but KP30086 lost both. Cloning of gene <i>bla</i><sub>CTX-M-71</sub> and conjugation experiment of <i>bla</i><sub>CTX-M-71</sub>-carrying plasmid showed that the transformant and transconjugant were susceptible to ceftazidime-avibactam but had a more than 8-fold increase in MICs. Supplementation with an outer membrane permeabilizer could reduce the MIC of ceftazidime-avibactam by 32 folds, indicating that porins play a key role in ceftazidime-avibactam resistance. The OmpK35 of the 3 isolates was not expressed, and the OmpK36 of KP29499 and KP30086 had a novel amino acid substitution (L359R). SDS-PAGE and qRT-PCR showed that the expression of porin OmpK36 of KP29499 and KP30086 was significantly down-regulated compared with KP29105.</p><p><strong>Conclusions: </strong>In summary, we reported the rare ceftazidime-avibactam resistance in a non-carbapenemase-producing hvKp strain. Resistance plasmid carrying <i>bla</i><sub>CTX-M-71</sub> and mutated OmpK36 had a synergetic effect on the resistance.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"15 1","pages":"2348251"},"PeriodicalIF":5.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11067985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140870775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-05-14DOI: 10.1080/21505594.2024.2350892
Qiu-Yan Xu, Xin-Qi Zheng, Wei-Ming Ye, Dong-Yu Yi, Ze Li, Qing-Qi Meng, Man-Li Tong, Dan Liu, Tian-Ci Yang
The evasive tactics of Treponema pallidum pose a major challenge in combating and eradicating syphilis. Natural killer (NK) cells mediate important effector functions in the control of pathogenic infection, preferentially eliminating targets with low or no expression of major histocompatibility complex (MHC) class I. To clarify T. pallidum's mechanisms in evading NK-mediated immunosurveillance, experiments were performed to explore the cross-talk relations among T. pallidum, NK cells, and platelets. T. pallidum adhered to, activated, and promoted particle secretion of platelets. After preincubation with T. pallidum, platelets expressed and secreted high levels of MHC class I, subsequently transferring them to the surface of T. pallidum, potentially inducing an immune phenotype characterized by the "pseudo-expression" of MHC class I on the surface of T. pallidum (hereafter referred to a "pseudo-expression" of MHC class I). The polA mRNA assay showed that platelet-preincubated T. pallidum group exhibited a significantly higher copy number of polA transcript than the T. pallidum group. The survival rate of T. pallidum mirrored that of polA mRNA, indicating that preincubation of T. pallidum with platelets attenuated NK cell lethality. Platelets pseudo-expressed the MHC class I ligand on the T. pallidum surface, facilitating binding to killer cell immunoglobulin-like receptors with two immunoglobulin domains and long cytoplasmic tail 3 (KIR2DL3) on NK cells and initiating dephosphorylation of Vav1 and phosphorylation of Crk, ultimately attenuating NK cell lethality. Our findings elucidate the mechanism by which platelets transfer MHC class I to the T. pallidum surface to evade NK cell immune clearance.
苍白盘尾丝菌的躲避策略给抗击和根除梅毒带来了重大挑战。为了弄清苍白螺旋体逃避NK介导的免疫监视的机制,研究人员进行了实验来探索苍白螺旋体、NK细胞和血小板之间的交叉对话关系。苍白球粘附、激活并促进血小板分泌微粒。与苍白球预孵育后,血小板表达并分泌高水平的 MHC I 类,随后将其转移到苍白球表面,可能诱导出一种以苍白球表面 MHC I 类 "伪表达"(以下简称 MHC I 类 "伪表达")为特征的免疫表型。polA mRNA 检测显示,血小板预培养 T. pallidum 组的 polA 转录本拷贝数明显高于 T. pallidum 组。T. pallidum的存活率与polA mRNA的存活率一致,这表明T. pallidum与血小板预孵育可减轻NK细胞的致死率。血小板在苍白球表面伪表达了MHC I类配体,促进了与NK细胞上具有两个免疫球蛋白结构域和长胞质尾3(KIR2DL3)的杀伤细胞免疫球蛋白样受体的结合,并启动了Vav1的去磷酸化和Crk的磷酸化,最终降低了NK细胞的致死率。我们的发现阐明了血小板将 MHC I 类转移到苍白球表面以逃避 NK 细胞免疫清除的机制。
{"title":"Platelet-derived major histocompatibility complex class I coating on <i>Treponema pallidum</i> attenuates natural killer cell lethality.","authors":"Qiu-Yan Xu, Xin-Qi Zheng, Wei-Ming Ye, Dong-Yu Yi, Ze Li, Qing-Qi Meng, Man-Li Tong, Dan Liu, Tian-Ci Yang","doi":"10.1080/21505594.2024.2350892","DOIUrl":"10.1080/21505594.2024.2350892","url":null,"abstract":"<p><p>The evasive tactics of <i>Treponema pallidum</i> pose a major challenge in combating and eradicating syphilis. Natural killer (NK) cells mediate important effector functions in the control of pathogenic infection, preferentially eliminating targets with low or no expression of major histocompatibility complex (MHC) class I. To clarify <i>T. pallidum's</i> mechanisms in evading NK-mediated immunosurveillance, experiments were performed to explore the cross-talk relations among <i>T. pallidum</i>, NK cells, and platelets. <i>T. pallidum</i> adhered to, activated, and promoted particle secretion of platelets. After preincubation with <i>T. pallidum</i>, platelets expressed and secreted high levels of MHC class I, subsequently transferring them to the surface of <i>T. pallidum</i>, potentially inducing an immune phenotype characterized by the \"pseudo-expression\" of MHC class I on the surface of <i>T. pallidum</i> (hereafter referred to a \"pseudo-expression\" of MHC class I). The <i>polA</i> mRNA assay showed that platelet-preincubated <i>T. pallidum</i> group exhibited a significantly higher copy number of <i>polA</i> transcript than the <i>T. pallidum</i> group. The survival rate of <i>T. pallidum</i> mirrored that of <i>polA</i> mRNA, indicating that preincubation of <i>T. pallidum</i> with platelets attenuated NK cell lethality. Platelets pseudo-expressed the MHC class I ligand on the <i>T. pallidum</i> surface, facilitating binding to killer cell immunoglobulin-like receptors with two immunoglobulin domains and long cytoplasmic tail 3 (KIR2DL3) on NK cells and initiating dephosphorylation of Vav1 and phosphorylation of Crk, ultimately attenuating NK cell lethality. Our findings elucidate the mechanism by which platelets transfer MHC class I to the <i>T. pallidum</i> surface to evade NK cell immune clearance.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"15 1","pages":"2350892"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140923261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}