{"title":"Impact of nutrients on the function of the chlamydial Rsb partner switching mechanism.","authors":"Shiomi Kuwabara, Evan R Landers, Derek J Fisher","doi":"10.1093/femspd/ftac044","DOIUrl":"10.1093/femspd/ftac044","url":null,"abstract":"<p><p>The obligate intracellular bacterial pathogen Chlamydia trachomatis is a leading cause of sexually transmitted infections and infectious blindness. Chlamydia undergo a biphasic developmental cycle alternating between the infectious elementary body (EB) and the replicative reticulate body (RB). The molecular mechanisms governing RB growth and RB-EB differentiation are unclear. We hypothesize that the bacterium senses host cell and bacterial energy levels and metabolites to ensure that development and growth coincide with nutrient availability. We predict that a partner switching mechanism (PSM) plays a key role in the sensing and response process acting as a molecular throttle sensitive to metabolite levels. Using purified wild type and mutant PSM proteins, we discovered that metal type impacts enzyme activity and the substrate specificity of RsbU and that RsbW prefers ATP over GTP as a phosphate donor. Immunoblotting analysis of RsbV1/V2 demonstrated the presence of both proteins beyond 20 hours post infection and we observed that an RsbV1-null strain has a developmental delay and exhibits differential growth attenuation in response to glucose levels. Collectively, our data support that the PSM regulates growth in response to metabolites and further defines biochemical features governing PSM-component interactions which could help in the development of novel PSM-targeted therapeutics.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":"80 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2022-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12173453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10343554","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":"Pyp25α is required for male gametocyte exflagellation.","authors":"Chao Zhang, Deyi Li, Zhirong Meng, Jianwei Zhou, Zhenxiao Min, Shengqun Deng, Jijia Shen, Miao Liu","doi":"10.1093/femspd/ftac043","DOIUrl":"https://doi.org/10.1093/femspd/ftac043","url":null,"abstract":"<p><p>Malaria, a mosquito-borne infectious disease, is caused by the unicellular apicomplexan protozoa of the genus Plasmodium. For malaria parasite transmission, the essential sexual stage includes production of gametocytes through gametocytogenesis in vertebrate hosts and formation of gametes from gametocytes through gametogenesis in mosquito vectors. Whereas each female gametocyte forms a single immotile macrogamete, a male gametocyte produces eight flagella-like microgametes in a process called exflagellation. We identified a conserved protein named as Py05543 (Pyp25α), required for male gametocyte exflagellation in Plasmodium yoelii, which is the ortholog of PFL1770c (PF3D7_1236600). Interestingly, PF3D7_1236600 was previously phenotypically screened to be gametocyte-essential genes during gametocytogenesis of Plasmodium falciparum, using piggyBac transposon-mediated insertional mutagenesis. In this study, using CRISPR/Cas9-mediated genome editing, the Pyp25α¯ (KO) parasite line was successfully established. We found that the KO parasites proliferated asexually in mouse blood normally. In addition, compared with that of the parental parasites, the KO parasites displayed similar levels of gametocytes formation. Unexpectedly, the KO parasites showed considerable deficiency in exflagellation of male gametes, by observing exflagellation centre formation. Taken together, our data suggested that Pyp25α gene, the ortholog of PF3D7_1236600, was nonessential for the growth of asexual parasites, required for male gametocyte exflagellation in P. yoelii.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2022-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40446813","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}
Dalia S Ashour, Fatma M Kh Ibrahim, Amira M Elshamy, Hager S Zoghroban
{"title":"Trichinella spiralis-derived extracellular vesicles induce a protective immunity against larval challenge in mice.","authors":"Dalia S Ashour, Fatma M Kh Ibrahim, Amira M Elshamy, Hager S Zoghroban","doi":"10.1093/femspd/ftac040","DOIUrl":"https://doi.org/10.1093/femspd/ftac040","url":null,"abstract":"<p><p>Human trichinellosis is a serious disease with no effective treatment till now. Recently, the protective immunity induced by parasite-derived extracellular vesicles (EVs) are studied for some parasites such as Echinostoma caproni. The current study aimed to investigate the novel Trichinella spiralis-derived EVs as a potential vaccine candidate for the first time in a mouse model. Trichinella spiralis EVs were isolated and identified using transmission electron microscopy, gel electrophoresis, protein content measurements, and beads-based flow cytometry. Vaccination was done by subcutaneous injection of two doses of 3.5 μg T. spiralis-derived EVs. We observed a significant reduction in T. spiralis adult worm and muscle larval counts in mice immunized with T. spiralis-derived EVs (EVs-Ts group) and controlled inflammatory changes in the intestine and muscles. The EVs-Ts group showed a higher level of IFN- γ, whereas the IL-4 secretion was elevated more in the EVs group (EVs group) and showed a lower level after challenge with T. spiralis infection (EVs-Ts group). This implies a mixed Th1/Th2 immune response with obvious Th1 polarization. Moreover, elevation of serum T. spiralis-specific IgG was reported. In conclusion, this preliminary study provides T. spiralis EVs as a promising candidate for future development of anti-Trichinella vaccine.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2022-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40557786","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":"Proteomic profiling of extracellular vesicles derived from ARPE-19 cells challenged with Aspergillus flavus and Candida albicans: application in fungal endophthalmitis.","authors":"Jaishree Gandhi, Joveeta Joseph","doi":"10.1093/femspd/ftac042","DOIUrl":"https://doi.org/10.1093/femspd/ftac042","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are nano-sized-particles that play an important role in cellular cross-talk. The aim of this study was to understand the proteomic cargo of EVs, released by Retinal Pigment Epithelial (RPE) cells challenged with Candida albicans (C-CA) and Aspergillus flavus (C-AF). EVs were isolated from culture supernatant of retinal cells infected with fungal pathogens and characterized by dynamic light scattering, SEM, and western blot. EV proteome was then evaluated by mass spectrometry (LC-MS/MS). Isolated EVs were approximately 120-150 nm and higher in number in infected group compared to control. Proteomic profiling of EVs from infected cells, showed a total of 419 and 254 differentially expressed proteins, of which 218 were upregulated in C-CA group and 81 proteins were upregulated in C-AF group. Gene ontology revealed majority of proteins associated with transport, cell migration, and in activation of innate immune response. Proteins identified were annexins, calpain, and Sorcin proteins. Additionally, KEGG analysis unveiled involvement of MAPK, HIF-1, and PI3K-AKT signalling pathways. Proteomic results indicate that EVs cargo derived from fungal-infected retinal cells can activate immune signalling pathways and might contribute to the pathogenesis of endophthalmitis, indicating the potential use of EVs as theranostic marker for management of fungal infections.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2022-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40428584","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":"Being the Alice of academia: lessons from the Red Queen hypothesis.","authors":"S G Negatu, M C Arreguin, K A Jurado, C Vazquez","doi":"10.1093/femspd/ftac034","DOIUrl":"https://doi.org/10.1093/femspd/ftac034","url":null,"abstract":"<p><p>Viruses and hosts must navigate environments in which each tries to outcompete the other for survival or to coexist within the same spaces. In Lewis Carrol's Through the Looking Glass, the Red Queen tells Alice, \"Now, here, you see, it takes all the running you can do, to keep in the same place. If you want to get somewhere else, you must run at least twice as fast as that!\" Borrowing from this idea, the Red Queen hypothesis asserts that organisms, such as viruses, must continuously adapt to environmental pressures to survive. In this commentary, we draw parallels between the Red Queen hypothesis and the experiences scientists of color navigate to thrive in academic spaces. In both phenomena, adapting to environmental pressures is necessary for survival. We identify the various pressures and bottlenecks faced by historically underrepresented groups in academia, as well as the adaptation strategies they must implement to persist in academia.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2022-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9629500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40357568","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}
Andres Ceballos-Garzon, Angela B Muñoz, Juan D Plata, Zilpa A Sanchez-Quitian, Jose Ramos-Vivas
{"title":"Phages, anti-CRISPR proteins, and drug-resistant bacteria: what do we know about this triad?","authors":"Andres Ceballos-Garzon, Angela B Muñoz, Juan D Plata, Zilpa A Sanchez-Quitian, Jose Ramos-Vivas","doi":"10.1093/femspd/ftac039","DOIUrl":"https://doi.org/10.1093/femspd/ftac039","url":null,"abstract":"<p><p>Phages are viruses that infect bacteria, relying on their genetic machinery to replicate. To survive the constant attack of phages, bacteria have developed diverse defense strategies to act against them. Nevertheless, phages rapidly co-evolve to overcome these barriers, resulting in a constant, and often surprising, molecular arms race. Thus, some phages have evolved protein inhibitors known as anti-CRISPRs (∼50-150 amino acids), which antagonize the bacterial CRISPR-Cas immune response. To date, around 45 anti-CRISPRs proteins with different mechanisms and structures have been discovered against the CRISPR-Cas type I and type II present in important animal and human pathogens such as Escherichia, Morganella, Klebsiella, Enterococcus, Pseudomonas, Staphylococcus, and Salmonella. Considering the alarming growth of antibiotic resistance, phage therapy, either alone or in combination with antibiotics, appears to be a promising alternative for the treatment of many bacterial infections. In this review, we illustrated the biological and clinical aspects of using phage therapy; furthermore, the CRISPR-Cas mechanism, and the interesting activity of anti-CRISPR proteins as a possible weapon to combat bacteria.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2022-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40338420","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}
Gabrielle Gimenes Lima, Amanda Izeli Portilho, Elizabeth De Gaspari
{"title":"Adjuvants to increase immunogenicity of SARS-CoV-2 RBD and support maternal-fetal transference of antibodies in mice.","authors":"Gabrielle Gimenes Lima, Amanda Izeli Portilho, Elizabeth De Gaspari","doi":"10.1093/femspd/ftac038","DOIUrl":"https://doi.org/10.1093/femspd/ftac038","url":null,"abstract":"<p><p>Adjuvants are important components of vaccines, increasing immunogenicity and modulating the immune response. SARS-CoV-2 vaccines are still being developed in order to improve worldwide access to immunization. Specific populations should be addressed in these investigations, such as pregnant women-to protect both mothers and neonates. In this study, female adult mice were immunized with Receptor-binding domain (RBD) from SARS-CoV-2 adjuvanted by a mixture of DDA and Saponin and put to mating to verify the maternal transference of IgG. For comparison, other group received RBD adjuvanted by OMVs from Neisseria meningitidis and Alum. The adjuvants enhanced IgG production and neutralization. DDA/Sap contributed to increase IgG1, IgG2a, IgG2b, and IgG3 isotypes. Total IgG avidity was considered high, as well as IgG1, IgG2a, and IgG2b avidity. IgG antibodies were effectively transferred to the offspring, predominantly IgG2a, IgG2b, and IgG3. The passive transferred immunoglobulin maintained the neutralizing ability, although it lost avidity. ELISA data was confirmed in Dot-ELISA and immunoblotting assays. DDA and Saponin seem a promising adjuvant mixture to enhance the humoral response of SARS-CoV-2 antigens. Further studies considering the effects of maternal immunization in the protection of offspring are needed, regardless the platform used in COVID-19 vaccines.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":"80 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2022-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9620730/pdf/ftac038.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9254779","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":"Construction and characterization of the full-length cDNA of an infectious clone of emerging porcine teschovirus-2.","authors":"Yuying Li, Shengnan Chen, Yaokai Shi, Haixin Huang, Wei Wang, Min Zheng, Chenchen Zhao, Xinyu Zhang, Xiaoxiao Lei, Wenchao Sun, Hao Liu, Tian Lan","doi":"10.1093/femspd/ftac033","DOIUrl":"https://doi.org/10.1093/femspd/ftac033","url":null,"abstract":"<p><p>Porcine teschovirus (PTV) is a causative agent of polioencephalomyelitis, encephalomyelitis, reproductive disorders and gastrointestinal and respiratory diseases in swine. In the present study, the PTV2 GX/2020 strain was isolated from pig intestinal tissue through the use of ST cells. Phylogenetic analysis of VP1 nucleotide sequences indicated that the GX/2020 isolate is closely related to PTV2. Furthermore, the full-length cDNA of an infectious GX/2020 clone was constructed using seamless ligation technology. The genome sequence of the rescued virus is largely consistent with the sequence of the parental virus, and it exhibits viral growth properties. The PTV2 virus was successfully isolated in the present study, and the reverse-genetic platform provides a foundation for studies of the pathogenic mechanisms of porcine teschovirus.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2022-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40334836","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}
Zubair Hussain, She Pengfei, Li Yimin, Liu Shasha, Li Zehao, Yang Yifan, Li Linhui, Zhou Linying, Wu Yong
{"title":"Study on antibacterial effect of halicin (SU3327) against Enterococcus faecalis and Enterococcus faecium.","authors":"Zubair Hussain, She Pengfei, Li Yimin, Liu Shasha, Li Zehao, Yang Yifan, Li Linhui, Zhou Linying, Wu Yong","doi":"10.1093/femspd/ftac037","DOIUrl":"https://doi.org/10.1093/femspd/ftac037","url":null,"abstract":"<p><p>Enterococci are important pathogens of nosocomial infections and are increasingly difficult to treat due to their intrinsic and acquired resistance to a range of antibiotics. Therefore, there is an urgent need to develop novel antibacterial agents, while drug repurposing is a promising approach to address this issue. Our study aimed to determine the antimicrobial efficacy of halicin against enterococci and found that the minimum inhibitory concentrations (MIC) of halicin against different strains of Enterococcus faecalis and Enterococcus faecium ranged from 4 to 8 μg/ml. In addition, the synergistic antibacterial effect between halicin and doxycycline (DOX) against Enterococcus was observed through the checkerboard method, and it was observed that halicin and DOX could significantly synergistically inhibit biofilm formation and eradicate preformed biofilms at sub-MICs. Moreover, the electron microscope results revealed that halicin could also disrupt the bacterial cell membrane at high concentrations. Furthermore, it is also confirmed that the combination of halicin and DOX has no significant cytotoxic effect on erythrocytes and other human-derived cells. In addition, the mouse subcutaneous model and H&E staining showed that the combination of halicin and DOX could effectively reduce the bacterial load and inflammatory infiltration without obvious side effects. In nutshell, these results demonstrate the potential of halicin in combination with DOX as a novel therapy against infections by Enterococcus.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2022-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33492560","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":"Involvement of the Noncanonical Polyadenylation Polymerase Cid14 in Fungal Azole Resistance in the Pathogen Cryptococcus neoformans.","authors":"Chenxi Li, Sihui Zhen, Xiaoyu Ma, Lan Ma, Zhen Wang, Ping Zhang, Xudong Zhu","doi":"10.1093/femspd/ftac036","DOIUrl":"https://doi.org/10.1093/femspd/ftac036","url":null,"abstract":"<p><p>The yeast noncanonical polyadenylation polymerase Cid14 was originally identified from fission yeast and plays a critical role in the TRAMP complex. This protein is a cytoplasmic cofactor and regulator of RNA-degrading exosomes. Cid14 is highly conserved from yeast to animals and has been demonstrated to play key roles in the regulation of RNA surveillance, nutrition metabolism, and growth in model organisms, but not yet in Cryptococcus neoformans (C. neoformans). Here, we report the identification of a gene encoding an equivalent Cid14 protein, named CID14, in the fungal pathogen C. neoformans. To obtain insights into the function of Cid14, we created a mutant strain, cid14Δ, with the CRISPR-Cas9 editing tool. Disruption of CID14 impaired cell membrane stability. Further investigations revealed the defects of the cid14Δ mutant in resistance to low carbohydrate levels. Meanwhile, significantly, the ability to grow under flucytosine stress was decreased in the cid14Δ mutant. More importantly, our results showed that the cid14Δ mutant does not affect yeast virulence but exhibits multidrug resistance to azole. Our work is the first to suggest that Cid14 plays critical roles in azole resistance by affecting Afr1, which is chiefly responsible for azole excretion in the ABC (ATP-binding cassette) transporter.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2022-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40374799","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}