Pathogens and disease最新文献_第4页

Leishmania LPG interacts with LRR5/LRR6 of macrophage TLR4 for parasite invasion and impairs the macrophage functions. 利什曼原虫LPG与巨噬细胞TLR4的LRR5/LRR6相互作用以进行寄生虫入侵并损害巨噬细胞功能。

IF 3.3 4区医学

Pathogens and disease Pub Date : 2023-01-17 DOI: 10.1093/femspd/ftad019

Sayani Mazumder, Archana Sinha, Sanhita Ghosh, Gurumayum Chourajit Sharma, Biswa Mohan Prusty, Debasis Manna, Durba Pal, Chiranjib Pal, Suman Dasgupta

{"title":"Leishmania LPG interacts with LRR5/LRR6 of macrophage TLR4 for parasite invasion and impairs the macrophage functions.","authors":"Sayani Mazumder, Archana Sinha, Sanhita Ghosh, Gurumayum Chourajit Sharma, Biswa Mohan Prusty, Debasis Manna, Durba Pal, Chiranjib Pal, Suman Dasgupta","doi":"10.1093/femspd/ftad019","DOIUrl":"10.1093/femspd/ftad019","url":null,"abstract":"Visceral leishmaniasis (VL) is a severe form of leishmaniasis, primarily affecting the poor in developing countries. Although several studies have highlighted the importance of toll-like receptors (TLRs) in the pathophysiology of leishmaniasis, the role of specific TLRs and their binding partners involved in Leishmania donovani uptake are still elusive. To investigate the mechanism of L. donovani entry inside the macrophages, we found that the parasite lipophosphoglycan (LPG) interacted with the macrophage TLR4, leading to parasite uptake without any significant alteration of macrophage cell viability. Increased parasite numbers within macrophages markedly inhibited lipopolysachharide-induced pro-inflammatory cytokines gene expression. Silencing of macrophage-TLR4, or inhibition of parasite-LPG, significantly stemmed parasite infection in macrophages. Interestingly, we observed a significant enhancement of macrophage migration, and generation of reactive oxygen species (ROS) in the parasite-infected TLR4-silenced macrophages, whereas parasite infection in TLR4-overexpressed macrophages exhibited a notable reduction of macrophage migration and ROS generation. Moreover, mutations in the leucine-rich repeats (LRRs), particularly LRR5 and LRR6, significantly prevented TLR4 interaction with LPG, thus inhibiting cellular parasite entry. All these results suggest that parasite LPG recognition by the LRR5 and LRR6 of macrophage-TLR4 facilitated parasite entry, and impaired macrophage functions. Therefore, targeting LRR5/LRR6 interactions with LPG could provide a novel option to prevent VL.","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10413977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ERK inhibition aids IFN-β promoter activation during EV71 infection by blocking CRYAB degradation in SH-SY5Y cells. 通过阻断SH-SY5Y细胞中CRYAB的降解，ERK抑制有助于EV71感染期间IFN-β启动子的激活。

IF 3.3 4区医学

Pathogens and disease Pub Date : 2023-01-17 DOI: 10.1093/femspd/ftad011

Dengming Chen, Cheng Chen, Jingyu Tan, Jing Yang, Bangtao Chen

{"title":"ERK inhibition aids IFN-β promoter activation during EV71 infection by blocking CRYAB degradation in SH-SY5Y cells.","authors":"Dengming Chen, Cheng Chen, Jingyu Tan, Jing Yang, Bangtao Chen","doi":"10.1093/femspd/ftad011","DOIUrl":"https://doi.org/10.1093/femspd/ftad011","url":null,"abstract":"Enterovirus 71 (EV71) can cause severe hand-foot-and-mouth disease with neurological complications. It has evolved multiple mechanisms to compromise the host type I interferon (IFN-I) response. In neuronal cells, EV71-mediated IFN-I antagonism may be associated with neural precursor cell-expressed developmentally downregulated 4-like (Nedd4L), the E3 ubiquitin ligase that can interact with alphaB-crystallin (CRYAB) in the regulation of Nav1.5 stability. Here, we investigated the effect of CRYAB stability on IFN-β promoter activity in neuronal SH-SY5Y cells infected with EV71, and its relations to Nedd4 L and extracellular signal-regulated kinases (ERK). Results showed that EV71 infection significantly caused CRYAB degradation via the Nedd4L-proteasome pathway, which required ERK-mediated phosphorylation of Serine 45 in CRYAB. Subsequently, it was observed that siRNA- or EV71-mediated CRYAB reduction limited Poly(dAT)-activated IFN-β promoter, and CRYAB stabilisation by U0126-mediated inhibition of ERK activation remarkably enhanced the activity of IFN-β promoter upon EV71 challenge. Collectively, we elucidate a novel mechanism by which ERK activation contributes to EV71 immune escape via CRYAB/IFN-β axis in SH-SY5Y cells, indicating that perturbing ERK activation is desirable for anti-EV71 therapy.","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9794810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In vitro and in vivo evaluation of DNase I in reinstating antibiotic efficacy against Klebsiella pneumoniae biofilms. 体外和体内评价dna酶I对肺炎克雷伯菌生物膜恢复抗生素疗效的作用。

IF 3.3 4区医学

Pathogens and disease Pub Date : 2023-01-17 DOI: 10.1093/femspd/ftad001

Anayata Sharma, Praveen Rishi, Rachna Singh

{"title":"In vitro and in vivo evaluation of DNase I in reinstating antibiotic efficacy against Klebsiella pneumoniae biofilms.","authors":"Anayata Sharma, Praveen Rishi, Rachna Singh","doi":"10.1093/femspd/ftad001","DOIUrl":"https://doi.org/10.1093/femspd/ftad001","url":null,"abstract":"Klebsiella pneumoniae is an opportunistic pathogen associated with biofilm-based infections, which are intrinsically antibiotic resistant. Extracellular DNA plays a crucial role in biofilm formation and self-defence, with nucleases being proposed as promising agents for biofilm disruption. This study evaluated the in vitro and in vivo efficacy of DNase I in improving the activity of cefotaxime, amikacin, and ciprofloxacin against K. pneumoniae biofilms. K. pneumoniae ATCC 700603 and a clinical isolate from catheter-related bloodstream infection were cultured for biofilm formation on microtiter plates, and the antibiofilm activity of the antibiotics (0.03-64 mg/L), with or without bovine pancreatic DNase I (1-32 mg/L) was determined by XTT dye reduction test and viable counting. The effect of ciprofloxacin (2 mg/L) and DNase I (16 mg/L) was further evaluated in vitro on 1-cm-long silicon catheter segments, and in a mouse model of subcutaneous catheter-associated infection. Combination with DNase I did not improve the biofilm-preventive capacity of the three antibiotics or the biofilm-eradicating capacity of cefotaxime and amikacin. The biofilm-eradicating capacity of ciprofloxacin was increased by 8-fold and 4-fold in K. pneumoniae ATCC 700603 and clinical isolate, respectively, with DNase I. The combination therapy caused 99% reduction in biofilm biomass in the mouse model.","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10875075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Immunotherapies for the prevention and treatment of Staphylococcus aureus infections: updates and challenges. 预防和治疗金黄色葡萄球菌感染的免疫疗法:最新进展和挑战。

IF 3.3 4区医学

Pathogens and disease Pub Date : 2023-01-17 DOI: 10.1093/femspd/ftad016

Pooi Yin Chung

引用次数: 1

Correction: Probiotics in vaginal health. 更正：阴道健康中的益生菌。

IF 3.3 4区医学

Pathogens and disease Pub Date : 2023-01-17 DOI: 10.1093/femspd/ftad027

引用次数: 0

Comparative study of GBP recruitment on two cytosol-dwelling pathogens, Francisella novicida and Shigella flexneri highlights differences in GBP repertoire and in GBP1 motif requirements. 对新弗朗西斯菌（Francisella novicida）和弗氏志贺氏菌（Shigella flexneri）这两种在细胞质中生存的病原体的 GBP 招募进行的比较研究，凸显了 GBP 基因库和 GBP1 动机要求的差异。

IF 3.3 4区医学

Pathogens and disease Pub Date : 2023-01-17 DOI: 10.1093/femspd/ftad005

Stanimira V Valeva, Manon Degabriel, Fanny Michal, Gabrielle Gay, John R Rohde, Felix Randow, Brice Lagrange, Thomas Henry

{"title":"Comparative study of GBP recruitment on two cytosol-dwelling pathogens, Francisella novicida and Shigella flexneri highlights differences in GBP repertoire and in GBP1 motif requirements.","authors":"Stanimira V Valeva, Manon Degabriel, Fanny Michal, Gabrielle Gay, John R Rohde, Felix Randow, Brice Lagrange, Thomas Henry","doi":"10.1093/femspd/ftad005","DOIUrl":"10.1093/femspd/ftad005","url":null,"abstract":"Guanylate-Binding Proteins are interferon-inducible GTPases that play a key role in cell autonomous responses against intracellular pathogens. Despite sharing high sequence similarity, subtle differences among GBPs translate into functional divergences that are still largely not understood. A key GBP feature is the formation of supramolecular GBP complexes on the bacterial surface. Such complexes are observed when GBP1 binds lipopolysaccharide (LPS) from Shigella and Salmonella and further recruits GBP2-4. Here, we compared GBP recruitment on two cytosol-dwelling pathogens, Francisella novicida and S. flexneri. Francisella novicida was coated by GBP1 and GBP2 and to a lower extent by GBP4 in human macrophages. Contrary to S. flexneri, F. novicida was not targeted by GBP3, a feature independent of T6SS effectors. Multiple GBP1 features were required to promote targeting to F. novicida while GBP1 targeting to S. flexneri was much more permissive to GBP1 mutagenesis suggesting that GBP1 has multiple domains that cooperate to recognize F. novicida atypical LPS. Altogether our results indicate that the repertoire of GBPs recruited onto specific bacteria is dictated by GBP-specific features and by specific bacterial factors that remain to be identified.","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9465932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Metalloproteome of human-infective RNA viruses: a study towards understanding the role of metal ions in virology. 人类感染性核糖核酸病毒的金属蛋白酶组：一项了解金属离子在病毒学中作用的研究。

IF 3.3 4区医学

Pathogens and disease Pub Date : 2023-01-17 DOI: 10.1093/femspd/ftad020

Himisha Dixit, Mahesh Kulharia, Shailender Kumar Verma

{"title":"Metalloproteome of human-infective RNA viruses: a study towards understanding the role of metal ions in virology.","authors":"Himisha Dixit, Mahesh Kulharia, Shailender Kumar Verma","doi":"10.1093/femspd/ftad020","DOIUrl":"10.1093/femspd/ftad020","url":null,"abstract":"Metalloproteins and metal-based inhibitors have been shown to effectively combat infectious diseases, particularly those caused by RNA viruses. In this study, a diverse set of bioinformatics methods was employed to identify metal-binding proteins of human RNA viruses. Seventy-three viral proteins with a high probability of being metal-binding proteins were identified. These proteins included 40 zinc-, 47 magnesium- and 14 manganese-binding proteins belonging to 29 viral species and eight significant viral families, including Coronaviridae, Flaviviridae and Retroviridae. Further functional characterization has revealed that these proteins play a critical role in several viral processes, including viral replication, fusion and host viral entry. They fall under the essential categories of viral proteins, including polymerase and protease enzymes. Magnesium ion is abundantly predicted to interact with these viral enzymes, followed by zinc. In addition, this study also examined the evolutionary aspects of predicted viral metalloproteins, offering essential insights into the metal utilization patterns among different viral species. The analysis indicates that the metal utilization patterns are conserved within the functional classes of the proteins. In conclusion, the findings of this study provide significant knowledge on viral metalloproteins that can serve as a valuable foundation for future research in this area.","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10132057","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

Identification of a novel transport system in Borrelia burgdorferi that links the inner and outer membranes. 确定鲍曼不动杆菌中连接内膜和外膜的新型运输系统。

IF 2.7 4区医学

Pathogens and disease Pub Date : 2023-01-17 DOI: 10.1093/femspd/ftad014

Hannah G Bowen, Melisha R Kenedy, David K Johnson, Alexander D MacKerell, Darrin R Akins

{"title":"Identification of a novel transport system in Borrelia burgdorferi that links the inner and outer membranes.","authors":"Hannah G Bowen, Melisha R Kenedy, David K Johnson, Alexander D MacKerell, Darrin R Akins","doi":"10.1093/femspd/ftad014","DOIUrl":"10.1093/femspd/ftad014","url":null,"abstract":"Borrelia burgdorferi, the spirochete that causes Lyme disease, is a diderm organism that is similar to Gram-negative organisms in that it contains both an inner and outer membrane. Unlike typical Gram-negative organisms, however, B. burgdorferi lacks lipopolysaccharide (LPS). Using computational genome analyses and structural modeling, we identified a transport system containing six proteins in B. burgdorferi that are all orthologs to proteins found in the lipopolysaccharide transport (LPT) system that links the inner and outer membranes of Gram-negative organisms and is responsible for placing LPS on the surface of these organisms. While B. burgdorferi does not contain LPS, it does encode over 100 different surface-exposed lipoproteins and several major glycolipids, which like LPS are also highly amphiphilic molecules, though no system to transport these molecules to the borrelial surface is known. Accordingly, experiments supplemented by molecular modeling were undertaken to determine whether the orthologous LPT system identified in B. burgdorferi could transport lipoproteins and/or glycolipids to the borrelial outer membrane. Our combined observations strongly suggest that the LPT transport system does not transport lipoproteins to the surface. Molecular dynamic modeling, however, suggests that the borrelial LPT system could transport borrelial glycolipids to the outer membrane.","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10353723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9897869","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

Editorial: making the invisible visible in STEMM. 社论：使不可见的STEMM可见。

IF 2.7 4区医学

Pathogens and disease Pub Date : 2023-01-17 DOI: 10.1093/femspd/ftad023

Antentor Hinton, Haysetta D Shuler

引用次数: 0

Colonization efficiency of multidrug-resistant Neisseria gonorrhoeae in a female mouse model. 耐多药淋病奈瑟菌在雌性小鼠模型中的定殖效率。

IF 3.3 4区医学

Pathogens and disease Pub Date : 2023-01-17 DOI: 10.1093/femspd/ftad030

Babatomiwa Kikiowo, Aloka B Bandara, Nader S Abutaleb, Mohamed N Seleem

{"title":"Colonization efficiency of multidrug-resistant Neisseria gonorrhoeae in a female mouse model.","authors":"Babatomiwa Kikiowo, Aloka B Bandara, Nader S Abutaleb, Mohamed N Seleem","doi":"10.1093/femspd/ftad030","DOIUrl":"10.1093/femspd/ftad030","url":null,"abstract":"The rapid occurrence of gonococcal resistance to all classes of antibiotics could lead to untreatable gonorrhea. Thus, development of novel anti-Neisseria gonorrhoeae drugs is urgently needed. Neisseria gonorrhoeae FA1090 is the most used in gonococcal infection mouse models because of its natural resistance to streptomycin. Streptomycin inhibits the urogenital commensal flora that permits gonococcal colonization. However, this strain is drug-susceptible and cannot be used to investigate the efficacy of novel agents against multidrug-resistant N. gonorrhoeae. Hence, to test the in vivo efficacy of new therapeutics against N. gonorrhoeae resistant to the frontline antibiotics, azithromycin, or ceftriaxone, we constructed streptomycin-resistant mutants of N. gonorrhoeae CDC-181 (azithromycin-resistant) and WHO-X (ceftriaxone-resistant). We identified the inoculum size needed to successfully colonize mice. Both mutants, CDC-181-rpsLA128G and WHO-X-rpsLA128G, colonized the genital tract of mice for 14 days with 100% colonization observed for at least 7 days. CDC-181-rpsLA128G demonstrated better colonization of the murine genital tract compared to WHO-X-rpsLA128G. Lower inoculum of WHO-X-rpsLA128G (105 and 106 CFU) colonized mice better than higher inoculum. Overall, our results indicate that CDC-181-rpsLA128G and WHO-X-rpsLA128G can colonize the lower genital tract of mice and are suitable to be used in mouse models to investigate the efficacy of antigonococcal agents.","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49680818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0