{"title":"Invasive candidiasis in Africa, what is the current picture?","authors":"C. A. Okoye, E. Nweze, C. Ibe","doi":"10.1093/femspd/ftac012","DOIUrl":"https://doi.org/10.1093/femspd/ftac012","url":null,"abstract":"Invasive candidiasis is a serious, progressive, and potentially deadly infection that can affect the brain, heart, bones, eyes, and other parts of the body. It is associated with risk factors such as the use of indwelling medical devices and prolonged hospital stay, and broad-spectrum antibiotics use. It is especially seen in immunocompromised individuals such as patients with prolonged hospital stay, gastrointestinal surgery, haematological malignancies, and respiratory diseases. We have conducted a systematic search of literature using a select group of database and appropriate search words and found that in Africa, there are 18,293 documented/reported cases of invasive candidiasis in the last few decades (1976-2021) and 16,636(91%) were cases of candidaemia. South Africa had the highest number of reported cases - 15,002(82%), which may be due to underreporting of cases in other countries. HIV positive persons with invasive candidiasis in Africa accounted for 1,052(5.8%). C. albicans was the most frequently isolated species 6,328(32.6%), followed by Candida parapsilosis 5,910(30.4%), and Candida auris 1,505(7.8%). Due to the affordability and availability of blood culture, it was used for diagnosis in most of the studies examined, while a few studies combined other techniques and just 3 studies from 2 countries used serological tests. Echinocandins are recommended as first-line therapy but are only available in 12 countries and are highly priced. The use of fluconazole because of its availability and relatively inexpensive nature has led to increased resistance of Candida species to the drug.","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":"1 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2022-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60710566","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}
C. Moreau, Andrea M. Darby, A. Demery, Lina M Arcila Hernández, Clara L. Meaders
{"title":"A framework for educating and empowering students by teaching about history and consequences of bias in STEM","authors":"C. Moreau, Andrea M. Darby, A. Demery, Lina M Arcila Hernández, Clara L. Meaders","doi":"10.1093/femspd/ftac006","DOIUrl":"https://doi.org/10.1093/femspd/ftac006","url":null,"abstract":"Abstract Racism and bias are pervasive in society—and science, technology, engineering, and mathematics (STEM) fields are not immune to these issues. It is imperative that we educate ourselves and our students about the history and consequences of this bias in STEM, investigate the research showing bias toward marginalized groups, understand how to interpret misuses of science in perpetuating bias, and identify advances and solutions to overcome racism and bias throughout our professional and personal lives. Here, we present one model for teaching a universal course for participants of all professional stages to address these issues and initiate solutions. As very few institutions require students to enroll in courses on racism and bias in STEM or even offer such courses, our curriculum could be used as a blueprint for implementation across institutions. Ultimately, institutions and academic disciplines can incorporate this important material with more region and/or discipline specific studies of bias.","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2022-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47012621","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}
Cameron Mandel, Hong Yang, G. W. Buchko, J. Abendroth, N. Grieshaber, Travis Chiarelli, S. Grieshaber, Anders Omsland
{"title":"Expression and structure of the Chlamydia trachomatis DksA ortholog","authors":"Cameron Mandel, Hong Yang, G. W. Buchko, J. Abendroth, N. Grieshaber, Travis Chiarelli, S. Grieshaber, Anders Omsland","doi":"10.1093/femspd/ftac007","DOIUrl":"https://doi.org/10.1093/femspd/ftac007","url":null,"abstract":"Abstract Chlamydia trachomatis is a bacterial obligate intracellular parasite and a significant cause of human disease, including sexually transmitted infections and trachoma. The bacterial RNA polymerase-binding protein DksA is a transcription factor integral to the multicomponent bacterial stress response pathway known as the stringent response. The genome of C. trachomatis encodes a DksA ortholog (DksACt) that is maximally expressed at 15–20 h post infection, a time frame correlating with the onset of transition between the replicative reticulate body (RB) and infectious elementary body (EB) forms of the pathogen. Ectopic overexpression of DksACt in C. trachomatis prior to RB–EB transitions during infection of HeLa cells resulted in a 39.3% reduction in overall replication (yield) and a 49.6% reduction in recovered EBs. While the overall domain organization of DksACt is similar to the DksA ortholog of Escherichia coli (DksAEc), DksACt did not functionally complement DksAEc. Transcription of dksACt is regulated by tandem promoters, one of which also controls expression of nrdR, encoding a negative regulator of deoxyribonucleotide biosynthesis. The phenotype resulting from ectopic expression of DksACt and the correlation between dksACt and nrdR expression is consistent with a role for DksACt in the C. trachomatis developmental cycle.","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2022-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43034569","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":"Retraction to: mitogen-activated protein kinases regulate mycobacterium avium-induced tumor necrosis factor-α release from macrophages.","authors":"","doi":"10.1093/femspd/ftac041","DOIUrl":"https://doi.org/10.1093/femspd/ftac041","url":null,"abstract":"","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":"80 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2022-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10475258","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}
Madison Greer, Jacob H Elnaggar, Christopher M Taylor, Li Shen
{"title":"Mycoplasma decontamination in Chlamydia trachomatis culture: a curative approach.","authors":"Madison Greer, Jacob H Elnaggar, Christopher M Taylor, Li Shen","doi":"10.1093/femspd/ftab056","DOIUrl":"https://doi.org/10.1093/femspd/ftab056","url":null,"abstract":"<p><p>Mycoplasma contamination of cell culture represents a serious problem in research and decontamination from cell-propagated obligate intracellular bacteria has proven challenging. Here, we presented an optimized protocol to remove Mycoplasma from contaminated Chlamydia trachomatis culture. A stepwise procedure of Mycoplasma removal entails (i) incubation in nonionic detergent-containing solution and (ii) separation of viable chlamydial organisms by fluorescence-activated cell sorting (FACS), followed by subcloning using a focus-forming assay. We also adapted a polymerase chain reaction (PCR) assay using paired universal and Mycoplasma-specific primers, which are distinguishable from the C. trachomatis counterparts, in combination with Sanger sequencing to determine the presence of mycoplasmas' 16S rRNA genes. These integrated approaches allow for full removal of Mycoplasma, as verified by the improved PCR assay, without compromising the capacity of viable C. trachomatis to adapt to new infection in epithelial cells. Some pitfalls during the Mycoplasma decontamination process are discussed.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":"79 9","pages":""},"PeriodicalIF":3.3,"publicationDate":"2022-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8759436/pdf/ftab056.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10358708","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":"Can't live outside you: a thematic issue on obligate intracellular bacterial pathogens.","authors":"Jörn Coers, Hayley J Newton, Jason A Carlyon","doi":"10.1093/femspd/ftab054","DOIUrl":"10.1093/femspd/ftab054","url":null,"abstract":"","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":"79 9","pages":""},"PeriodicalIF":2.7,"publicationDate":"2021-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8664538/pdf/ftab054.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10371326","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}
Yating Liao, Xiangying Deng, Kailan Peng, Pei Dai, Dan Luo, Peng Liu, Liesong Chen, Xia Li, Youyuan Ye, Yanhua Zeng
{"title":"Identification of histone H2B as a potential receptor for Mycoplasma genitalium protein of adhesion.","authors":"Yating Liao, Xiangying Deng, Kailan Peng, Pei Dai, Dan Luo, Peng Liu, Liesong Chen, Xia Li, Youyuan Ye, Yanhua Zeng","doi":"10.1093/femspd/ftab053","DOIUrl":"https://doi.org/10.1093/femspd/ftab053","url":null,"abstract":"<p><p>Mycoplasma genitalium, the smallest prokaryotic microorganism capable of independent replication, is increasingly recognized as a sexually transmitted pathogen. M. genitalium protein of adhesion (MgPa) plays a pivotal role in the process of M. genitalium adhesion to host cells. We previously identified cyclophilin A as a cellular receptor of MgPa using the virus overlay protein binding assay (VOPBA) together with liquid chromatography-mass spectrometry (LC-MS). In the current study, we have evaluated H2B as an alternative cellular receptor for MgPa since H2B was assigned the second higher score as a potential binding partner of MgPa in the VOPBA and LC-MS screen. It was found that recombinant MgPa specifically bind to H2B both in the SV-HUC-1 cell membrane and in form of a recombinant protein. H2B was detected throughout the SV-HUC-1 cells, including the cytoplasmic membrane, cytosol and nucleus. Importantly, H2B partially inhibited the adhesion of M. genitalium to SV-HUC-1 cells. Finally, H2B was both co-precipitated with recombinant MgPa and co-localized with M. genitalium and recombinant MgPa in SV-HUC-1 cells. The above observations suggest that H2B may act as a potential cellular receptor of MgPa for mediating M. genitalium adhesion to host cells.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":"79 7","pages":""},"PeriodicalIF":3.3,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39859388","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":"Delineating infection strategies of Leishmania donovani secretory proteins in Human through host-pathogen protein Interactome prediction.","authors":"Gauri Panditrao, Piyali Ganguli, Ram Rup Sarkar","doi":"10.1093/femspd/ftab051","DOIUrl":"https://doi.org/10.1093/femspd/ftab051","url":null,"abstract":"<p><p>Interactions of Leishmania donovani secretory virulence factors with the host proteins and their interplay during the infection process in humans is poorly studied in Visceral Leishmaniasis. Lack of a holistic study of pathway level de-regulations caused due to these virulence factors leads to a poor understanding of the parasite strategies to subvert the host immune responses, secure its survival inside the host and further the spread of infection to the visceral organs. In this study, we propose a computational workflow to predict host-pathogen protein interactome of L.donovani secretory virulence factors with human proteins combining sequence-based Interolog mapping and structure-based Domain Interaction mapping techniques. We further employ graph theoretical approaches and shortest path methods to analyze the interactome. Our study deciphers the infection paths involving some unique and understudied disease-associated signaling pathways influencing the cellular phenotypic responses in the host. Our statistical analysis based in silico knockout study unveils for the first time UBC, 1433Z and HS90A mediator proteins as potential immunomodulatory candidates through which the virulence factors employ the infection paths. These identified pathways and novel mediator proteins can be effectively used as possible targets to control and modulate the infection process further aiding in the treatment of Visceral Leishmaniasis.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":"79 8","pages":""},"PeriodicalIF":3.3,"publicationDate":"2021-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39540556","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}
V. Edwards, Elias McComb, Jason P. Gleghorn, L. Forney, P. Bavoil, J. Ravel
{"title":"Three-dimensional models of the cervicovaginal epithelia to study host–microbiome interactions and sexually transmitted infections","authors":"V. Edwards, Elias McComb, Jason P. Gleghorn, L. Forney, P. Bavoil, J. Ravel","doi":"10.1101/2021.11.04.467382","DOIUrl":"https://doi.org/10.1101/2021.11.04.467382","url":null,"abstract":"Two-dimensional (2D) cell culture systems have provided controlled, reproducible means to analyze host-pathogen interactions. Although inexpensive, straightforward, and requiring very short time commitment, these models recapitulate neither the functionality of multi-layered cell types nor the microbial diversity of an infected human. Animal models have commonly been used to recreate the complexity of human infections. However, extensive modifications are commonly required to recreate interactions that resemble those in the human reproductive tract microbiologically and physiologically. Three-dimensional (3D) cell culture models have emerged as alternative means of reproducing key elements of human infections at a fraction of the cost of animal models and on a scale that allows for replicative experiments to be readily performed. Here we describe a new 3D model that utilizes transwells with epithelial cells seeded apically and a basolateral extra cellular matrix (ECM)-like layer containing collagen and fibroblasts. In this system, basal feeding creates a liquid/air interface on the apical side. The model produced tissues with close morphologic and physiological resemblance to human cervical and vaginal epithelia, including observable levels of mucus produced by cervical cells. Infection by both Chlamydia trachomatis and Neisseria gonorrhoeae was demonstrated as well as the growth of bacterial species observed in the human vaginal microbiota, enabling controlled mechanistic analyses of the interactions between host cells, vaginal microbiota and STI pathogens. Future experiments may include immune cells to mimic more closely the genital environment. Finally, the modular set up of the model makes it fully applicable to the analysis of non-genital host-microbiome-pathogen interactions. IMPORTANCE Infected sites in humans are a complex mix of host and microbial cell types interacting with each other to perform specific and necessary functions. The ability to understand the mechanism(s) that facilitate these interactions, and interactions with external factors is paramount to being able to develop preventative therapies. Models that attempt to faithfully replicate the complexity of these interactions are time intensive, costly, and not conducive to high throughput analysis. Two-dimensional (2D) models that have been used as a platform to understand these interactions, while cost effective, are generally limiting in experimental flexibility and structural/physiological relevance. Our three-dimensional (3D) models of the cervicovaginal epithelium can facilitate analysis of interactions between the host epithelium, sexually transmitted pathogens and bacteria present in the vaginal microbiota. Due to the modular design, additional cell types and environmental modulators can be introduced to the system to provide added complexity, approaching conditions in the infected human host.","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":"80 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2021-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49209164","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":"Virophages: association with human diseases and their predicted role as virus killers.","authors":"Debrupa Dutta, Velayutham Ravichandiran, Soumi Sukla","doi":"10.1093/femspd/ftab049","DOIUrl":"https://doi.org/10.1093/femspd/ftab049","url":null,"abstract":"<p><p>The fascinating discovery of the first giant virus, Acanthamoeba polyphaga mimivirus (APMV), belonging to the family Mimiviridae in 2008, and its associated virophage, Sputnik, have left the world of microbiology awestruck. To date, about 18 virophages have been isolated from different environmental sources. With their unique feature of resisting host cell infection and lysis by giant viruses, analogous to bacteriophage, they have been assigned under the family Lavidaviridae. Genome of T-27, icosahedral-shaped, non-enveloped virophages, consist of dsDNA encoding four proteins, namely, major capsid protein, minor capsid protein, ATPase and cysteine protease, which are essential in the formation and assembly of new virophage particles during replication. A few virophage genomes have been observed to contain additional sequences like PolB, ZnR and S3H. Another interesting characteristic of virophage is that Mimivirus lineage A is immune to infection by the Zamilon virophage through a phenomenon termed MIMIVIRE, resembling the CRISPR-Cas mechanism in bacteria. Based on the fact that giant viruses have been found in clinical samples of hospital-acquired pneumonia and rheumatoid arthritis patients, virophages have opened a novel era in the search for cures of various diseases. This article aims to study the prospective role of virophages in the future of human therapeutics.</p>","PeriodicalId":19795,"journal":{"name":"Pathogens and disease","volume":"79 8","pages":""},"PeriodicalIF":3.3,"publicationDate":"2021-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39482206","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}