{"title":"The potential role of Protein disulfide isomerases (PDIs) during parasitic infections: A focus on Leishmania spp.","authors":"Majid Dousti, Masoumeh Hosseinpour, Nadia DarestaniGhasemi, Hosna Mirfakhraee, Shahin Keshtkar Rajabi, Sajad Rashidi, Gholamreza Hatam","doi":"10.1093/femspd/ftad032","DOIUrl":"https://doi.org/10.1093/femspd/ftad032","url":null,"abstract":"Leishmaniasis is a group of vector-borne diseases caused by intracellular protozoan parasites belonging to the genus Leishmania. Leishmania parasites can employ different and numerous sophisticated strategies including modulating host proteins, cell signaling, and cell responses by parasite proteins to change the infected host conditions to favor the parasite persistence and induce pathogenesis. In this sense, Protein Disulfide Isomerases (PDIs) have been described as crucial proteins that can be modulated during leishmaniasis and affect the pathogenesis process. The effect of modulated PDIs can be investigated in both aspects, parasite-PDIs, and infected host cells-PDIs, during infection. The information concerning PDIs is not sufficient in parasitology; however, this study aimed to provide data regarding the biological functions of such crucial proteins in parasites with a focus on Leishmania spp. and their relevant effects on the pathogenesis process. Although there are no clinical trial vaccines and therapeutic approaches, highlighting this information might be fruitful for the development of novel strategies based on PDIs for the management of parasitic diseases, especially leishmaniasis.","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":"8 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138554800","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}
{"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":"<p><p>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.</p>","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":"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}
Beatriz Souza Toscano de Melo, Danilo Elias Xavier, Nilma Cintra Leal, Túlio de Lima Campos
{"title":"High prevalence of GR2 and GR4 plasmids in Acinetobacter baumannii strains from Brazil.","authors":"Beatriz Souza Toscano de Melo, Danilo Elias Xavier, Nilma Cintra Leal, Túlio de Lima Campos","doi":"10.1093/femspd/ftad022","DOIUrl":"10.1093/femspd/ftad022","url":null,"abstract":"<p><p>Acinetobacter baumannii is Gram-negative pathogen with extensive role in healthcare-associated infections (HAIs). Plasmids in this species are important carriers of antimicrobial resistance genes. In this work, we investigated the plasmids of 227 Brazilian A. baumannii genomes. A total of 389 plasmid sequences with 424 Rep proteins typed to 22 different homology groups (GRs) were identified. The GR2 plasmid group was the most predominant (40.6%), followed by the GR4 group (16.7%), representing ∼57% of all plasmids. There is a wide distribution of plasmids among the isolates and most strains carry more than one plasmid. Our analyses revealed a significant prevalence of GR4 plasmids in Brazilian A. baumannii genomes carrying several antimicrobial resistance genes, notably to carbapenem (39.43%). These plasmids harbor a MOBQ relaxase that might confer increased spreading potential in the environment. Most plasmids of the predominant groups belong to the same plasmid taxonomic unit (PTU-Pse7) and have a AbkA/AbkB toxin-antitoxin system that has a role in plasmid stability and dissemination of carbapenem resistance genes. The results of this work should contribute to our understanding of the molecular content of plasmids in a large and populous country, highlighting the importance of genomics for enhanced epidemiological surveillance.</p>","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":"10143543","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}
{"title":"Immunotherapies for the prevention and treatment of Staphylococcus aureus infections: updates and challenges.","authors":"Pooi Yin Chung","doi":"10.1093/femspd/ftad016","DOIUrl":"https://doi.org/10.1093/femspd/ftad016","url":null,"abstract":"<p><p>Staphylococcus aureus is the leading cause of hospital-acquired infections and can cause a wide range of diseases from mild skin infections to invasive diseases including deep surgical site infections, life-threatening bacteremia, and sepsis. This pathogen remains a challenge to manage due to its ability to rapidly develop resistance to antibiotic treatment and to form biofilms. Despite the current infection control measures which involve mainly antibiotics, the burden of infection remains high. The 'omics' approaches have not led to the discovery of novel antibacterials at a pace sufficient to cope with the emergence of multidrug-resistant and biofilm-forming S. aureus, Hence, new strategies for anti-infective therapies need to be explored urgently. One promising strategy is harnessing the immune response to enhance the protective antimicrobial immunity in the host. This review discusses the potential of monoclonal antibodies and vaccines as alternatives to treat and manage infections caused by planktonic and biofilms of S. aureus.</p>","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":"10275123","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}
{"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":"<p><p>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.</p>","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":"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}
{"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":"<p><p>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.</p>","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":"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}
{"title":"Correction: Probiotics in vaginal health.","authors":"","doi":"10.1093/femspd/ftad027","DOIUrl":"10.1093/femspd/ftad027","url":null,"abstract":"More active advantageous organisms may be developed as new probiotic strains for treating bacterial vaginitis.","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":"41208258","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}
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":"<p><p>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.</p>","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}
{"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":"<p><p>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.</p>","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}
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":"<p><p>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.</p>","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}