Pathogens and disease最新文献_第5页

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":"81 ","pages":""},"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

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":" ","pages":""},"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

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":"81 ","pages":""},"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

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

Comparative transcriptomics and genomics from continuous axenic media growth identifies Coxiella burnetii intracellular survival strategies. 连续轴生培养基生长的转录组学和基因组学比较确定了烧伤柯西氏菌的胞内生存策略。

IF 3.3 4区医学

Pathogens and disease Pub Date : 2023-01-17 DOI: 10.1093/femspd/ftad009

Archana Yadav, Melissa N Brewer, Mostafa S Elshahed, Edward I Shaw

{"title":"Comparative transcriptomics and genomics from continuous axenic media growth identifies Coxiella burnetii intracellular survival strategies.","authors":"Archana Yadav, Melissa N Brewer, Mostafa S Elshahed, Edward I Shaw","doi":"10.1093/femspd/ftad009","DOIUrl":"10.1093/femspd/ftad009","url":null,"abstract":"Coxiella burnetii (Cb) is an obligate intracellular pathogen in nature and the causative agent of acute Q fever as well as chronic diseases. In an effort to identify genes and proteins crucial to their normal intracellular growth lifestyle, we applied a 'reverse evolution' approach where the avirulent Nine Mile Phase II strain of Cb was grown for 67 passages in chemically defined ACCM-D media and gene expression patterns and genome integrity from various passages was compared to passage number one following intracellular growth. Transcriptomic analysis identified a marked downregulation of the structural components of the type 4B secretion system (T4BSS), the general secretory (Sec) pathway, as well as 14 out of 118 previously identified genes encoding effector proteins. Additional downregulated pathogenicity determinants genes included several chaperones, LPS, and peptidoglycan biosynthesis. A general marked downregulation of central metabolic pathways was also observed, which was balanced by a marked upregulation of genes encoding transporters. This pattern reflected the richness of the media and diminishing anabolic, and ATP-generation needs. Finally, genomic sequencing and comparative genomic analysis demonstrated an extremely low level of mutation across passages, despite the observed Cb gene expression changes following acclimation to axenic media.","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":"81 ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2023-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10237335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10125158","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

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":" ","pages":""},"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

Impact of IL-17-producing γδ T cells on chronic otitis media induced by nontypeable Haemophilus influenzae in a mouse model. 在小鼠模型中产生IL-17的γδT细胞对非分型流感嗜血杆菌诱导的慢性中耳炎的影响。

IF 3.3 4区医学

Pathogens and disease Pub Date : 2023-01-17 DOI: 10.1093/femspd/ftad029

Takashi Hirano, Toshiaki Kawano, Yoshinori Kadowaki, Munehito Moriyama, Shingo Umemoto, Kazuhiro Yoshinaga, Takayuki Matsunaga, Masashi Suzuki

{"title":"Impact of IL-17-producing γδ T cells on chronic otitis media induced by nontypeable Haemophilus influenzae in a mouse model.","authors":"Takashi Hirano, Toshiaki Kawano, Yoshinori Kadowaki, Munehito Moriyama, Shingo Umemoto, Kazuhiro Yoshinaga, Takayuki Matsunaga, Masashi Suzuki","doi":"10.1093/femspd/ftad029","DOIUrl":"10.1093/femspd/ftad029","url":null,"abstract":"Nontypeable Haemophilus influenzae (NTHi) is considered a major pathogen underlying middle ear infection. This study aimed to investigate the impact of IL-17 on chronic otitis media (COM) induced by NTHi in mice. NTHi was inoculated into the tympanic bulla with eustachian tubal obstruction. Middle ear effusions (MEEs) and tissues were collected on days 3, 14, and at 1, 2, and 6 months after injection. The expression of interleukin-17A (IL-17A) in MEEs was significantly elevated compared to that in the control group at the translational and transcriptional levels during the experiments. The quantities of IL-17-producing γδ T cells were significantly increased compared to that in the control group during COM, but that of Th17 cells did not. Depletion of γδ T cells by anti-γδ T-cell receptor (TCR) monoclonal antibody (mAb) administration significantly decreased the bacteria counts and the concentrations of IL-1β, IL-6, IL-17A, TNF-α, and IL-10 in MEEs. Our results suggest that IL-17 may play an important role in prolonging the inflammation in the middle ear in COM and that IL-17-producing γδ T cells may contribute to the exacerbated inflammatory response in the middle ear. In this study, anti-γδ TCR mAb administration was found to improve chronic middle ear inflammatory conditions.","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2023-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41208256","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

Strategies for change: thriving as an individual with a disabilty in STEMM. 改变的策略:在stem中作为一个残疾人茁壮成长。

IF 3.3 4区医学

Pathogens and disease Pub Date : 2023-01-17 DOI: 10.1093/femspd/ftac045

Amber Crabtree, Kit Neikirk, Andrea Marshall, Taylor Barongan, Heather K Beasley, Edgar Garza Lopez, Dominique Stephens, Sandra Murray, Elsie C Spencer, Denise Martinez, Chia Vang, Felysha Jenkins, Steven Damo, Zer Vue

引用次数: 1

Leishmania amazonensis infection impairs VLA-4 clustering and adhesion complex assembly at the adhesion site of J774 cells. 亚马逊利什曼原虫感染使J774细胞黏附部位的VLA-4聚集和黏附复合物组装受损。

IF 3.3 4区医学

Pathogens and disease Pub Date : 2023-01-17 DOI: 10.1093/femspd/ftad013

Reginaldo Brito, Erina Masayo Hassegawa, Patrick Camardelli, Kalene Elpídio, Juliana de Menezes, Cláudio Pereira Figueira, Washington L C Dos-Santos

{"title":"Leishmania amazonensis infection impairs VLA-4 clustering and adhesion complex assembly at the adhesion site of J774 cells.","authors":"Reginaldo Brito, Erina Masayo Hassegawa, Patrick Camardelli, Kalene Elpídio, Juliana de Menezes, Cláudio Pereira Figueira, Washington L C Dos-Santos","doi":"10.1093/femspd/ftad013","DOIUrl":"https://doi.org/10.1093/femspd/ftad013","url":null,"abstract":"Cutaneous leishmaniasis is an infectious disease that may lead to a single or multiple disseminated cutaneous lesions. The mechanisms involved in Leishmania dissemination to different areas of the skin and the internal organs remain poorly understood. Evidence shows that Very Late Antigen-4 (VLA-4)-dependent phagocyte adhesion is impaired by Leishmania infection, which may be related to the mechanisms of parasite dissemination. We investigated factors potentially associated with decreased VLA-4-mediated adhesion in Leishmania-infected macrophages, including lipid raft-mediated VLA-4 mobilization along the cellular membrane, integrin cluster formation at the cell base (adhesion site), and focal adhesion complex assembly. Phagocytes treated with Methyl-β-Cyclodextrin (MβCD) demonstrated reduced adhesion, similarly to Leishmania amazonensis-infected J774 cells. Infected and MβCD-treated macrophages presented decreased VLA-4 mobilization to the adhesion plane, as well as reduced integrin clustering. Leishmania amazonensis-infected cells exhibited talin depletion, as well as a decreased mobilization of adhesion complex proteins, such as talin and viculin, which were associated with lower VLA-4 concentrations at the adhesion site and limited cell-spreading. Our results suggest that Leishmania infection may modulate the firm adhesion phase of the cell-spreading process, which could contribute to the bloodstream dissemination of infected cells.","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":"81 ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2023-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9908768","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

Clinical strains of Mycobacterium tuberculosis exhibit differential lipid metabolism-associated transcriptome changes in in vitro cholesterol and infection models. 结核分枝杆菌临床菌株在体外胆固醇和感染模型中表现出不同的脂质代谢相关转录组变化。

IF 3.3 4区医学

Pathogens and disease Pub Date : 2023-01-17 DOI: 10.1093/femspd/ftac046

Kynesha Moopanar, Asanda Nomfundo Graduate Nyide, Sibusiso Senzani, Nontobeko Eunice Mvubu

{"title":"Clinical strains of Mycobacterium tuberculosis exhibit differential lipid metabolism-associated transcriptome changes in in vitro cholesterol and infection models.","authors":"Kynesha Moopanar, Asanda Nomfundo Graduate Nyide, Sibusiso Senzani, Nontobeko Eunice Mvubu","doi":"10.1093/femspd/ftac046","DOIUrl":"https://doi.org/10.1093/femspd/ftac046","url":null,"abstract":"Many studies have identified host-derived lipids, characterised by the abundance of cholesterol, as a major source of carbon nutrition for Mycobacterium tuberculosis during infection. Members of the Mycobacterium tuberculosis complex are biologically different with regards to degree of disease, host range, pathogenicity and transmission. Therefore, the current study aimed at elucidating transcriptome changes during early infection of pulmonary epithelial cells and on an in vitro cholesterol-rich minimal media, in M. tuberculosis clinical strains F15/LAM4/KZN and Beijing, and the laboratory H37Rv strain. Infection of pulmonary epithelial cells elicited the upregulation of fadD28 and hsaC in both the F15/LAM4/KZN and Beijing strains and the downregulation of several other lipid-associated genes. Growth curve analysis revealed F15/LAM4/KZN and Beijing to be slow growers in 7H9 medium and cholesterol-supplemented media. RNA-seq analysis revealed strain-specific transcriptomic changes, thereby affecting different metabolic processes in an in vitro cholesterol model. The differential expression of these genes suggests that the genetically diverse M. tuberculosis clinical strains exhibit strain-specific behaviour that may influence their ability to metabolise lipids, specifically cholesterol, which may account for phenotypic differences observed during infection.","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":"81 ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2023-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9936260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9382274","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