Pathogens and disease最新文献_第10页

Coexistence of blaNDM-1, blaOXA-51, blaOXA-23 and armA in conjunction with novel mutations detected in RND efflux pump regulators in tigecycline resistant clinical isolates of Acinetobacter baumannii. 在对替加环素耐药的鲍曼不动杆菌临床分离株中检测到blaNDM-1、blaOXA-51、blaOXA-23和armA的共存以及RND外排泵调节因子的新突变。

IF 3.3 4区医学

Pathogens and disease Pub Date : 2022-06-15 DOI: 10.1093/femspd/ftac020

A. Sawant, Sudhakar Pagal, Ashutosh Kumar Amar, L. Panda, S. Devi C., P. Shashikala, R. Kanungo, K. Prashanth

{"title":"Coexistence of blaNDM-1, blaOXA-51, blaOXA-23 and armA in conjunction with novel mutations detected in RND efflux pump regulators in tigecycline resistant clinical isolates of Acinetobacter baumannii.","authors":"A. Sawant, Sudhakar Pagal, Ashutosh Kumar Amar, L. Panda, S. Devi C., P. Shashikala, R. Kanungo, K. Prashanth","doi":"10.1093/femspd/ftac020","DOIUrl":"https://doi.org/10.1093/femspd/ftac020","url":null,"abstract":"This study has investigated a total of 51 A. baumannii isolates for the prevalence of resistant determinants in tigecycline susceptible and non-susceptible clinical isolates of A. baumannii. Antimicrobial susceptibility testing revealed 74% of isolates were tigecycline resistant. Mutations in RND-efflux pump regulatory genes and the expression of efflux pump genes were measured in tigecycline resistant isolates. There was a strong co-relation between the blaNDM-1 and armA wherein majority of the isolates that are positive for blaNDM-1 have also harbored armA. Compared with TSAB (tigecycline susceptible A. baumannii), TNAB (tigecycline non-susceptible A. baumannii) isolates show increased distribution of blaNDM-1 (p = 0.048), blaIMP-1 (p<0.0001) and blaOXA-51 (p = 0.0029) carbapenemase genes. The variants of RND-efflux pump regulatory genes due to amino-acid mutations in adeS (F12S, K84E, W61R, N268H and Q299R) and adeL (G21R and Q262R) were identified in tigecycline resistant isolates as well as ISAba1 mediated disruption of adeN were observed causing overexpression of adeIJK efflux pump. Additionally, mutations in adeRS were also associated with increased expression of adeABC efflux pump. Besides, TNAB isolates showed significantly (p<0.0001) higher ability of biofilm formation as compared to TSAB isolates. The tigecycline resistance due to mutations in contemporary A. baumannii isolates having a higher ability to form biofilm may pose therapeutic difficulties.","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48021488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Immunopotentiation by linking Hsp70 T-cell epitopes to Gag-Pol-Env-Nef-Rev multiepitope construct and increased IFN-gamma secretion in infected lymphocytes. 通过将Hsp70 T细胞表位连接到Gag-Pol-Ev-Nef-Rev多表位构建体来增强免疫，并增加感染淋巴细胞中的IFN-γ分泌。

IF 3.3 4区医学

Pathogens and disease Pub Date : 2022-06-15 DOI: 10.1093/femspd/ftac021

E. Akbari, S. Ajdary, E. M. Ardakani, Elnaz Agi, A. Milani, Masoud Seyedinkhorasani, V. Khalaj, A. Bolhassani

{"title":"Immunopotentiation by linking Hsp70 T-cell epitopes to Gag-Pol-Env-Nef-Rev multiepitope construct and increased IFN-gamma secretion in infected lymphocytes.","authors":"E. Akbari, S. Ajdary, E. M. Ardakani, Elnaz Agi, A. Milani, Masoud Seyedinkhorasani, V. Khalaj, A. Bolhassani","doi":"10.1093/femspd/ftac021","DOIUrl":"https://doi.org/10.1093/femspd/ftac021","url":null,"abstract":"Therapeutic human immunodeficiency virus (HIV) vaccines can boost the anti-HIV host immunity to control viral replication and eliminate viral reservoirs in the absence of anti-retroviral therapy. In this study, two computationally designed multiepitope Gag-Pol-Env-Nef-Rev and Hsp70-Gag-Pol-Env-Nef-Rev constructs harboring immunogenic and highly conserved HIV T cell epitopes were generated in E. coli as polypeptide vaccine candidates. Furthermore, the multiepitope gag-pol-env-nef-rev and hsp70-gag-pol-env-nef-rev DNA vaccine constructs were prepared and complexed with MPG cell-penetrating peptide. The immunogenicity of the multiepitope constructs were evaluated using the homologous and heterologous prime/boost strategies in mice. Moreover, the secretion of IFN-γ was assessed in infected lymphocytes in vitro. Our data showed that the homologous polypeptide regimens could significantly induce a mixture of IgG1 and IgG2a antibody responses, activate T cells to secret IFN-γ, IL-5, IL-10, and generate Granzyme B. Moreover, IFN-γ secretion was significantly enhanced in single-cycle replicable (SCR) HIV-1 virions-infected splenocytes in these groups compared to uninfected splenocytes. The linkage of heat shock protein 70 (Hsp70) epitopes to Gag-Pol-Env-Nef-Rev polypeptide in the homologous regimen increased significantly cytokines and Granzyme B levels, and IFN-γ secretion in virions-infected splenocytes. Briefly, both designed constructs in the homologous regimens can be used as a promising vaccine candidate against HIV infection.","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47088597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

P. falciparum PfRUVBL proteins binds at TARE region and var gene promoter located in subtelomeric region. 恶性疟原虫PfRUVBL蛋白结合于TARE区，var基因启动子位于亚端粒区。

IF 3.3 4区医学

Pathogens and disease Pub Date : 2022-05-31 DOI: 10.1093/femspd/ftac018

H. Saxena, Ashish Gupta

{"title":"P. falciparum PfRUVBL proteins binds at TARE region and var gene promoter located in subtelomeric region.","authors":"H. Saxena, Ashish Gupta","doi":"10.1093/femspd/ftac018","DOIUrl":"https://doi.org/10.1093/femspd/ftac018","url":null,"abstract":"In order to survive and establish infection, Plasmodium parasite employ various strategies to evade host immune response. Var genes family, a repertoire of 60 genes, express parasite-specific protein PfEMP1, a variable surface antigen, on the membrane of infected erythrocyte, and by continuously switching the variants of PfEMP1, helps the parasite to avoid detection and destruction by host immune system during intra-erythrocytic developmental cycle. Although chromatin modifications are recognized to be a prominent phenomenon in regulation of mono-allelic expression of these var genes, however the precise histone codes and molecular players & mechanisms guiding these modifications are yet to be unravelled in depth. In this study, we have functionally characterized RUVBL proteins of P. falciparum and shown that PfMYST (an essential lysine acetyl transferase) and PfRUVBL protein complex occupy the TARE region and var gene promoter in ring stage of the parasite. Further we have demonstrated that PfMYST/PfRUVBL complex interact with core histone, H3 & H4. Overall the findings of this study adds a layer by identifying the potential role of epigenetic regulators, PfMYST & PfRUVBL in regulation of monoallelic expression of var genes in malaria parasite.","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43094655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

AZI2 positively regulates the induction of type I interferon in influenza-trigger pediatric pneumonia. AZI2正调控I型干扰素在流感引发的儿童肺炎中的诱导作用。

IF 3.3 4区医学

Pathogens and disease Pub Date : 2022-05-20 DOI: 10.1093/femspd/ftac016

Meili Wei, Ya-nan Zheng, Jing Xu, Qiwei Sun

{"title":"AZI2 positively regulates the induction of type I interferon in influenza-trigger pediatric pneumonia.","authors":"Meili Wei, Ya-nan Zheng, Jing Xu, Qiwei Sun","doi":"10.1093/femspd/ftac016","DOIUrl":"https://doi.org/10.1093/femspd/ftac016","url":null,"abstract":"5-azacytidine-induced protein 2 (AZI2) is known to have a crucial role in antiviral innate immunity. This study aims to explore the roles of AZI2 in influenza-trigger pediatric pneumonia and its molecular mechanism. qPCR and immunoblotting assays were used to determine the levels of target genes and proteins. The lung infection mouse model was established by using PR8 H1N1 virus in AZI2 germline knockout (AZI2-/-) and wide-type (WT) mice. In addition, HEK293T cell-based luciferase reporter assays were used to investigate the regulatory effects of AZI2 on type I interferon. Immune precipitation and immunofluorescence staining were used to evaluate the interactions between AZI2 and TANK binding kinase 1 (TBK1). We observed an elevation in the expressions of IFN-I and AZI2 in peripheral blood mononuclear cells from the pneumonia patients with mild symptoms. Interestingly, AZI2 deficiency deteriorated the influenza-induced pathological symptoms in the lung as well as reduced the survival rate. It was further showed that AZI2 positively regulated the expressions of type I interferon, inflammatory cytokines, and IFN production-related genes. The molecular mechanism data revealed that AZI2 regulated the interactions between TBK1 and TANK. In summary, AZI2 positively regulates type I interferon production in influenza-induced pediatric pneumonia by promoting the interactions between TBK1 and TANK.","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48079282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Title: A Comprehensive Review on Classifying Fast-acting and Slow-acting Antimalarial Agents Based on Time of Action and Target Organelle of Plasmodium sp. 题目:基于疟原虫作用时间和靶细胞器分类快效和慢效抗疟药的综述。

IF 3.3 4区医学

Pathogens and disease Pub Date : 2022-05-19 DOI: 10.1093/femspd/ftac015

Monika Marie Bernard, Abhinab Mohanty, V. Rajendran

{"title":"Title: A Comprehensive Review on Classifying Fast-acting and Slow-acting Antimalarial Agents Based on Time of Action and Target Organelle of Plasmodium sp.","authors":"Monika Marie Bernard, Abhinab Mohanty, V. Rajendran","doi":"10.1093/femspd/ftac015","DOIUrl":"https://doi.org/10.1093/femspd/ftac015","url":null,"abstract":"The clinical resistance towards malarial parasites has rendered many antimalarials ineffective, likely due to a lack of understanding of time of action and stage specificity of all life stages. Therefore, to tackle this problem a more incisive comprehensive analysis of the fast and slow-acting profile of antimalarial agents relating to parasite time-kill kinetics and the target organelle on the progression of blood-stage parasites was carried out. It is evident from numerous findings that drugs targeting food vacuole, nuclear components, and endoplasmic reticulum mainly exhibit a fast-killing phenotype within 24h affecting first-cycle activity. Whereas drugs targeting mitochondria, apicoplast, microtubules, parasite invasion and egress exhibit a largely slow-killing phenotype within 96-120h, affecting second-cycle activity with few exemptions as moderately fast-killing. It is essential to understand the susceptibility of drugs on rings, trophozoites, schizonts, merozoites, and the appearance of organelle at each stage of 48h intraerythrocytic parasite cycle. Therefore, these parameters may facilitate the paradigm for understanding the timing of antimalarials action in deciphering its precise mechanism linked with time. Thus, classifying drugs based on the time of killing may promote designing new combination regimens against varied strains of P. falciparum and evaluating potential clinical resistance.","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48308081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Discovery of spirooxindole-pyrrolidine heterocyclic hybrids with potent antifungal activity against fungal pathogens. 具有抗真菌活性的螺旋菌吲哚-吡咯烷杂环杂交种的发现。

IF 3.3 4区医学

Pathogens and disease Pub Date : 2022-05-05 DOI: 10.1093/femspd/ftac013

H. Dowdy, Raju Suresh Kumar, A. Almansour, N. Arumugam, Shatha IbrahimAlaqeel, Shankar Thangamani

引用次数: 0

Vitamin D-induced LL-37 modulates innate immune responses of human primary macrophages during DENV-2 infection. 维生素d诱导的LL-37在DENV-2感染期间调节人原代巨噬细胞的先天免疫反应。

IF 3.3 4区医学

Pathogens and disease Pub Date : 2022-05-05 DOI: 10.1093/femspd/ftac014

J. Castillo, Diana M Giraldo, J. Smit, Izabela A. Rodenhuis-Zybert, S. Urcuqui-Inchima

{"title":"Vitamin D-induced LL-37 modulates innate immune responses of human primary macrophages during DENV-2 infection.","authors":"J. Castillo, Diana M Giraldo, J. Smit, Izabela A. Rodenhuis-Zybert, S. Urcuqui-Inchima","doi":"10.1093/femspd/ftac014","DOIUrl":"https://doi.org/10.1093/femspd/ftac014","url":null,"abstract":"Epidemics of dengue, an acute and potentially severe disease caused by mosquito-borne dengue virus (DENV), pose a major challenge to clinicians and health care services across the sub(tropics). Severe disease onset is associated with a dysregulated inflammatory response to the virus and there are currently no drugs to alleviate disease symptoms. LL-37 is a potent antimicrobial peptide with a wide range of immunoregulatory properties. In this study, we assessed the effect of LL-37 on DENV-2-induced responses in human monocyte-derived macrophages (MDMs). We show that simultaneous exposure of exogenous LL-37 and DENV-2 resulted in reduced replication of the virus in MDMs, while the addition of LL-37 post-exposure to DENV-2 did not. Interestingly, the latter condition reduced the production of IL-6 and increased the expression of genes involved in virus sensing and antiviral response. Finally, we demonstrate that low endogenous levels and limited production of LL-37 in MDMs in response to DENV-2 infection can be increased by differentiating MDMs in the presence of Vitamin D (VitD3). Taken together, this study demonstrates that in addition to its antimicrobial properties, LL-37 has immunomodulatory properties in the curse of DENV infection and its production can be increased by VitD3.","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45428999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6

Inhibition of infection-induced vascular permeability modulates host leukocyte recruitment to Mycobacterium marinum granulomas in zebrafish. 抑制感染诱导的血管通透性可调节斑马鱼体内马氏分枝杆菌肉芽肿的宿主白细胞募集。

IF 2.7 4区医学

Pathogens and disease Pub Date : 2022-04-29 DOI: 10.1093/femspd/ftac009

Julia Y Kam, Tina Cheng, Danielle C Garland, Warwick J Britton, David M Tobin, Stefan H Oehlers

{"title":"Inhibition of infection-induced vascular permeability modulates host leukocyte recruitment to Mycobacterium marinum granulomas in zebrafish.","authors":"Julia Y Kam, Tina Cheng, Danielle C Garland, Warwick J Britton, David M Tobin, Stefan H Oehlers","doi":"10.1093/femspd/ftac009","DOIUrl":"10.1093/femspd/ftac009","url":null,"abstract":"Mycobacterial granuloma formation involves significant stromal remodeling including the growth of leaky, granuloma-associated vasculature. These permeable blood vessels aid mycobacterial growth, as antiangiogenic or vascular normalizing therapies are beneficial host-directed therapies in preclinical models of tuberculosis across host-mycobacterial pairings. Using the zebrafish-Mycobacterium marinum infection model, we demonstrate that vascular normalization by inhibition of vascular endothelial protein tyrosine phosphatase (VE-PTP) decreases granuloma hypoxia, the opposite effect of hypoxia-inducing antiangiogenic therapy. Inhibition of VE-PTP decreased neutrophil recruitment to granulomas in adult and larval zebrafish, and decreased the proportion of neutrophils that extravasated distal to granulomas. Furthermore, VE-PTP inhibition increased the accumulation of T cells at M. marinum granulomas. Our study provides evidence that, similar to the effect in solid tumors, vascular normalization during mycobacterial infection increases the T cell:neutrophil ratio in lesions which may be correlates of protective immunity.","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2022-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9053305/pdf/ftac009.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9326783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tannerella forsythia strains differentially induce interferon gamma-induced protein 10 (IP-10) expression in macrophages due to lipopolysaccharide heterogeneity. 由于脂多糖的异质性，单宁菌在巨噬细胞中诱导干扰素γ诱导蛋白10 (IP-10)的表达存在差异。

IF 3.3 4区医学

Pathogens and disease Pub Date : 2022-04-29 DOI: 10.1093/femspd/ftac008

Sreedevi Chinthamani, Rajendra P Settem, Kiyonobu Honma, Graham P Stafford, Ashu Sharma

{"title":"Tannerella forsythia strains differentially induce interferon gamma-induced protein 10 (IP-10) expression in macrophages due to lipopolysaccharide heterogeneity.","authors":"Sreedevi Chinthamani, Rajendra P Settem, Kiyonobu Honma, Graham P Stafford, Ashu Sharma","doi":"10.1093/femspd/ftac008","DOIUrl":"https://doi.org/10.1093/femspd/ftac008","url":null,"abstract":"Tannerella forsythia is strongly implicated in the development of periodontitis, an inflammatory disease that destroys the bone and soft tissues supporting the tooth. To date, the knowledge of the virulence attributes of T. forsythia species has mainly come from studies with a laboratory adapted strain (ATCC 43037). In this study, we focused on two T. forsythia clinical isolates, UB4 and UB20, in relation to their ability to activate macrophages. We found that these clinical isolates differentially induced proinflammatory cytokine expression in macrophages. Prominently, the expression of the chemokine protein IP-10 (CXCL10) was highly induced by UB20 as compared to UB4 and the laboratory strain ATCC 43037. Our study focused on the lipopolysaccharide component (LPS) of these strains and found that UB20 expressed a smooth-type LPS, unlike UB4 and ATCC 43037 each of which expressed a rough-type LPS. The LPS from UB20, via activation of TLR4, was found to be a highly potent inducer of IP-10 expression via signaling through STAT1 (signal transducer and activator of transcription-1). These data suggest that pathogenicity of T. forsythia species could be strain dependent and the LPS heterogeneity associated with the clinical strains might be responsible for their pathogenic potential and severity of periodontitis.","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9053306/pdf/ftac008.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9277979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Polymicrobial interaction in biofilm: mechanistic Insights. 生物膜中的多微生物相互作用：机理见解。

IF 3.3 4区医学

Pathogens and disease Pub Date : 2022-04-27 DOI: 10.1093/femspd/ftac010

Pratima Gupta, Anmol Kulshrestha

引用次数: 10