Cellular Microbiology最新文献

{"title":"Deletion of a Putative GPI-Anchored Protein-Encoding Gene Aog185 Impedes the Growth and Nematode-Trapping Efficiency of Arthrobotrys oligospora by Disrupting Transmembrane Transport Homeostasis","authors":"Hui Peng,&nbsp;Hengqian Lu,&nbsp;Xinyuan Dong,&nbsp;Xiao Liang,&nbsp;Kangliang Sheng,&nbsp;Jingmin Wang,&nbsp;Xiaowei Kong,&nbsp;Xiangdong Zha,&nbsp;Yongzhong Wang","doi":"10.1155/2022/8738290","DOIUrl":"10.1155/2022/8738290","url":null,"abstract":"<div>\u0000 <p>Nematode-trapping fungus (NTF) is a crucial predator of nematodes, which can capture nematodes by developing specific trapping devices. However, there is limited understanding of the role and mechanism of cell surface proteins attached to the surface of mycelia or trapping cells. Here, the effects of a putative GPI-anchored protein-encoding gene Ao<i>g185</i> on the growth and nematode-trapping efficiency of <i>A. oligospora</i> were investigated. Compared to the wild-type (WT) strain, the <i>Δ</i>Ao<i>g185</i> mutant grew more slowly, exhibited a 20% decrease in conidiation, delayed conidial germination, generated fewer traps, attenuated nematode trapping efficiency, and was more sensitive to chemical stressors. Transcriptomic analysis indicated that a large number of transmembrane transport-related genes were differentially expressed between the WT and <i>Δ</i>Ao<i>g185</i> mutant strains. Ao<i>g185</i> deletion could damage the intrinsic components of the membrane and cytoskeleton. Specifically, knockout of Ao<i>g185</i> disrupted transmembrane transport homeostasis during the phagocytosis, cell autophagy, and oxidative phosphorylation processes, which were associated with the fusion of cells and organelle membranes, transport of ions and substrates, and energy metabolism. Hence, the putative GPI-anchored protein-encoding gene Ao<i>g185</i> may contribute to the lifestyle switch of NTF and nematode capture, and the effect of Ao<i>g185</i> gene on cell transmembrane transport is considered key to this process. Our findings provide new insights into the mechanism of Ao<i>g185</i> gene during the process of nematode trapping by NTF.</p>\u0000 </div>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"2022 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2022-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2022/8738290","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46290763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Similarities and Differences among Species Closely Related to Candida albicans: C. tropicalis, C. dubliniensis, and C. auris","authors":"Dorota Satala,&nbsp;Magdalena Juszczak,&nbsp;Ewelina Wronowska,&nbsp;Magdalena Surowiec,&nbsp;Kamila Kulig,&nbsp;Andrzej Kozik,&nbsp;Maria Rapala-Kozik,&nbsp;Justyna Karkowska-Kuleta","doi":"10.1155/2022/2599136","DOIUrl":"10.1155/2022/2599136","url":null,"abstract":"<div>\u0000 <p>Although <i>Candida</i> species are widespread commensals of the microflora of healthy individuals, they are also among the most important human fungal pathogens that under certain conditions can cause diseases (candidiases) of varying severity ranging from mild superficial infections of the mucous membranes to life-threatening systemic infections. So far, the vast majority of research aimed at understanding the molecular basis of pathogenesis has been focused on the most common species—<i>Candida albicans</i>. Meanwhile, other closely related species belonging to the CTG clade, namely, <i>Candida tropicalis</i> and <i>Candida dubliniensis</i>, are becoming more important in clinical practice, as well as a relatively newly identified species, <i>Candida auris</i>. Despite the close relationship of these microorganisms, it seems that in the course of evolution, they have developed distinct biochemical, metabolic, and physiological adaptations, which they use to fit to commensal niches and achieve full virulence. Therefore, in this review, we describe the current knowledge on <i>C. tropicalis</i>, <i>C. dubliniensis</i>, and <i>C. auris</i> virulence factors, the formation of a mixed species biofilm and mutual communication, the environmental stress response and related changes in fungal cell metabolism, and the effect of pathogens on host defense response and susceptibility to antifungal agents used, highlighting differences with respect to <i>C. albicans</i>. Special attention is paid to common diagnostic problems resulting from similarities between these species and the emergence of drug resistance mechanisms. Understanding the different strategies to achieve virulence, used by important opportunistic pathogens of the genus <i>Candida</i>, is essential for proper diagnosis and treatment.</p>\u0000 </div>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"2022 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2022-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2022/2599136","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138518986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomolecules of the Horseshoe Crab’s Hemolymph: Components of an Ancient Defensive Mechanism and Its Impact on the Pharmaceutical and Biomedical Industry","authors":"Md. Ashrafuzzaman,&nbsp;Mamudul Hasan Razu,&nbsp;Nazmir-Nur Showva,&nbsp;Tohmina Afroze Bondhon,&nbsp;Md. Moniruzzaman,&nbsp;Sad Al Rezwan Rahman,&nbsp;Md. Raisul Islam Rabby,&nbsp;Fatema Akter,&nbsp;Mala Khan","doi":"10.1155/2022/3381162","DOIUrl":"10.1155/2022/3381162","url":null,"abstract":"<div>\u0000 <p>Without adaptive immunity, invertebrates have evolved innate immune systems that react to antigens on the surfaces of pathogens. These defense mechanisms are included in horseshoe crab hemocytes’ cellular responses to pathogens. Secretory granules, large (L) and small (S), are found on hemocytes. Once the invasion of pathogens is present, these granules release their contents through exocytosis. Recent data in biochemistry and immunology on the granular constituents of granule-specific proteins are stored in large and small granules which are involved in the cell-mediated immune response. L-granules contain most clotting proteins, which are necessary for hemolymph coagulation. They also include tachylectins; protease inhibitors, such as cystatin and serpins; and anti-lipopolysaccharide (LPS) factors, which bind to LPS and agglutinate bacteria. Big defensin, tachycitin, tachystatin, and tachyplesins are some of the essential cysteine-rich proteins in S-granules. These granules also contain tachycitin and tachystatins, which can agglutinate bacteria. These proteins in granules and hemolymph act synergistically to fight infections. These biomolecules are antimicrobial and antibacterial, enabling them to be drug resistant. This review is aimed at explaining the biomolecules identified in the horseshoe crab’s hemolymph and their application scopes in the pharmaceutical and biotechnology sectors.</p>\u0000 </div>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"2022 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2022-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2022/3381162","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45041757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pasteurella multocida Toxin Aggravates Ligatured-Induced Periodontal Bone Loss and Inflammation via NOD-Like Receptor Protein 3 Inflammasome","authors":"Yineng Han,&nbsp;Pengfei Gao,&nbsp;Qiaolin Yang,&nbsp;Yiping Huang,&nbsp;Lingfei Jia,&nbsp;Yunfei Zheng,&nbsp;Weiran Li","doi":"10.1155/2022/3305695","DOIUrl":"10.1155/2022/3305695","url":null,"abstract":"<div>\u0000 <p>NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is reportedly involved in periodontal pathogenesis. <i>Pasteurella multocida</i> toxin (PMT) is the major virulence factor of <i>Pasteurella multocida</i> strains, which belongs to the nonoral gram-negative facultative rods (GNFR). The existence of GNFR and their toxin may aggravate periodontitis. Therefore, it is important to unclose the regulatory mechanisms of PMT in periodontitis. However, the involvement of NLRP3 inflammasome and PMT in periodontitis remain unclear. The results showed that NLRP3 expression was increased in periodontitis mice by immunohistochemical staining and quantitative reverse transcription polymerase chain reaction (qRT-PCR). <i>Nlrp3</i>^-/- mice showed less periodontal bone loss and lower abundances of <i>Pasteurella multocida</i> by 16S rRNA sequencing. PMT promoted NLRP3 expressions by activating nuclear factor kappa light chain enhancer of B cells (NF-<i>κ</i>B) pathway and activated NLRP3 inflammasome. This effect was reversed by NLRP3 inhibitor MCC950. Furthermore, PMT aggravated periodontal bone loss and inflammation in WT mice, while MCC950 attenuated periodontal bone loss and inflammation. The <i>Nlrp3</i>^-/- periodontitis models with PMT local injection showed less bone loss and inflammation compared with WT periodontitis mice after PMT treatment. Taken together, our results showed that PMT aggravates periodontal response to the ligature by promoting NLRP3 expression and activating NLRP3 inflammasome, suggesting that NLRP3 may be an effective target for the treatment of periodontitis caused by GNFR and MCC950 may be a potential drug against this disease.</p>\u0000 </div>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"2022 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2022-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2022/3305695","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48645724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation between HPV PCNA, p16, and p21 Expression in Lung Cancer Patients","authors":"B. F. São Marcos,&nbsp;T. H. A. de Oliveira,&nbsp;C. M. M. Do Amaral,&nbsp;M. T. C. Muniz,&nbsp;A. C. Freitas","doi":"10.1155/2022/9144334","DOIUrl":"10.1155/2022/9144334","url":null,"abstract":"<div>\u0000 <p><i>Purpose</i>. Evaluate if human papillomavirus (HPV) infection in lung cancer patients might be helping cancer development by altering p16, p21, and PCNA, key human genes involved in cell proliferation and tumor development. <i>Methods</i>. 63 fresh-frozen (FF) and formalin-fixed paraffin-embedded (FFPE) samples from lung tumor patients were used to detect HPV by PCR, followed by genotype through sequencing. The host gene expressions of p21, p16, and PCNA were quantified by qPCR in both FF and FFPE samples, and the expression of viral oncogenes E5, E6, and E7 was also measured by qPCR in 19 FF samples. <i>Results</i>. 74.6% of samples were positive for HPV, 33/44 FFPE samples and 14/19 FF samples. HPV-16 and HPV-18 were detected in 31/33 and 7/33 FFPE, respectively, and HPV-16 was the only type in FF samples. E5, E6, and E7 were expressed in 10/19, 2/19, and 4/19 FF samples, respectively. The p16 RNAm expression was higher in FF HPV+ samples and FFPE+FF HPV+ samples, while p21 showed higher expression in all HPV- samples. In turn, the PCNA expression was higher in HPV+ FF samples; however, in FFPE and FFPE+FF samples, PCNA was higher in HPV- samples. In FF samples, PCNA, p16, and p21 showed a significant positive correlation as well as E5 and E7, and E5 was inversely correlated to p21. In FFPE, also, a positive correlation was observed between PCNA HPV+ and p21 HPV+ and PCNA HPV+ and p16 HPV. In FF+FFPE analysis, a direct correlation was found between PCNA HPV+ and p21 HPV+, p21 HPV+ and p16 HPV+, and PCNA HPV- and p16 HPV-, and an inverse correlation between PCNA HPV+ and p16 HPV+. Also, the p16 protein was positive in 10 HPV+ samples and 1 HPV-. <i>Conclusions</i>. Our data show that lung cancer patients from Northeast Brazil have a high prevalence of HPV, and the virus also expresses its oncogenes and correlates with key human genes involved in tumor development. This data could instigate the development of studies focused on preventive strategies, such as vaccination, used as a prognostic indicator and/or individualized therapy.</p>\u0000 </div>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"2022 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2022-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2022/9144334","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45554052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"lncRNA MANCR Inhibits NK Cell Killing Effect on Lung Adenocarcinoma by Targeting miRNA-30d-5p","authors":"Yunping Lu,&nbsp;Xiao Rao,&nbsp;Weifen Zheng,&nbsp;Yinggan Du,&nbsp;Jianbo Xue,&nbsp;Kan Huang","doi":"10.1155/2022/4928635","DOIUrl":"10.1155/2022/4928635","url":null,"abstract":"<div>\u0000 <p><i>Background</i>. NK cells are imperative in spontaneous antitumor response of various cancers. Currently, lncRNAs are considered important modulators of the tumor microenvironment. This study investigated the molecular mechanism by which mitotically associated long noncoding RNA (MANCR) controls killing effect of NK cells on lung adenocarcinoma (LUAD) in the tumor microenvironment. <i>Methods</i>. The interplay between MANCR and miRNA-30d-5p was analyzed by bioinformatics. Expression of MANCR mRNA and miRNA-30d-5p was examined using qRT-PCR. Dual-luciferase reporter and RIP assays were utilized to verify the targeted relationship between MANCR and miRNA-30d-5p. To investigate regulation of MANCR/miRNA-30d-5p axis in NK cell killing effect on LUAD cells, western blot tested the protein level of perforin and granzyme B. ELISA determined the level of IFN-<i>γ</i>. CytoTox 96 Non-Radioactive Cytotoxicity Assay kit was applied for cytotoxicity detection of NK cells. Perforin and granzyme B fluorescence intensity was measured via immunofluorescence, and cell apoptosis levels were also revealed via flow cytometry. <i>Results</i>. MANCR was found to be upregulated, while miRNA-30d-5p expression was downregulated in LUAD tissues. Overexpression of MANCR in LUAD cells significantly reduced NK cell IFN-<i>γ</i> secretion, expression of granzyme B and perforin, and NK cell killing effect. In addition, MANCR could target and downregulate miRNA-30d-5p expression, and miRNA-30d-5p overexpression reversed the inhibition of NK cell killing effect caused by MANCR overexpression. <i>Conclusion</i>. MANCR inhibited the killing effect of NK cells on LUAD via targeting and downregulating miRNA-30d-5p and provided new ideas for antitumor therapy based on tumor microenvironment.</p>\u0000 </div>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"2022 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2022-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2022/4928635","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46310364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Live Cell Imaging Microfluidic Model for Studying Extravasation of Bloodborne Bacterial Pathogens","authors":"Michele d. Bergevin,&nbsp;Anna E. Boczula,&nbsp;Laura-lee Caruso,&nbsp;Henrik Persson,&nbsp;Craig A. Simmons,&nbsp;Tara J. Moriarty","doi":"10.1155/2022/3130361","DOIUrl":"10.1155/2022/3130361","url":null,"abstract":"<div>\u0000 <p>Bacteria that migrate (extravasate) out of the bloodstream during vascular dissemination can cause secondary infections in many tissues and organs, including the brain, heart, liver, joints, and bone with clinically serious and sometimes fatal outcomes. The mechanisms by which bacteria extravasate through endothelial barriers in the face of blood flow-induced shear stress are poorly understood, in part because individual bacteria are rarely observed traversing endothelia <i>in vivo</i>, and <i>in vitro</i> model systems inadequately mimic the vascular environment. To enable the study of bacterial extravasation mechanisms, we developed a transmembrane microfluidics device mimicking human blood vessels. Fast, quantitative, three-dimensional live cell imaging in this system permitted single-cell resolution measurement of the Lyme disease bacterium <i>Borrelia burgdorferi</i> transmigrating through monolayers of primary human endothelial cells under physiological shear stress. This cost-effective, flexible method was 10,000 times more sensitive than conventional plate reader-based methods for measuring transendothelial migration. Validation studies confirmed that <i>B. burgdorferi</i> transmigrate actively and strikingly do so at similar rates under static and physiological flow conditions. This method has significant potential for future studies of <i>B. burgdorferi</i> extravasation mechanisms, as well as the transendothelial migration mechanisms of other disseminating bloodborne pathogens.</p>\u0000 </div>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"2022 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2022-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2022/3130361","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48364263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamics of DNA Replication during Male Gametogenesis in the Malaria Parasite Plasmodium Falciparum","authors":"Holly Matthews,&nbsp;Jennifer McDonald,&nbsp;Francis Isidore G. Totañes,&nbsp;Catherine J. Merrick","doi":"10.1155/2022/2701868","DOIUrl":"10.1155/2022/2701868","url":null,"abstract":"<div>\u0000 <p>Malaria parasites undergo a single phase of sexual reproduction in their complex lifecycle. It involves specialised, sexually committed cells called gametocytes, which develop rapidly into mature gametes and mate upon entering the mosquito midgut. Gamete development is unique, involving unprecedentedly fast replication to produce male gametes. Within ~15 minutes a male gametocyte replicates its ~23 Mb genome three times to produce 8 genomes, segregates these into newly-assembled flagellated gametes and releases them to seek female gametes. Here, for the first time, we use fluorescent labelling of <i>de novo</i> DNA synthesis to follow this process at the whole-cell and single-molecule levels. We make several novel observations, including characterising the origin recognition complex protein Orc1 for the first time in gametocytes, finding that cytokinesis is uncoupled from DNA replication (implying a lack of cell cycle checkpoints), and that the single-molecule dynamics of DNA replication are entirely different from the dynamics in asexual schizogony.</p>\u0000 </div>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"2022 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2022-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2022/2701868","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138518993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Modeling Guided Drug Designing for the Therapeutic Treatment of Rheumatoid Arthritis","authors":"Maheen Imran,&nbsp;Muhammad Hassan Nasir,&nbsp;Syed Awais Attique,&nbsp;Atif Amin Baig,&nbsp;Qurat Ul Ain,&nbsp;Muhammad Usman,&nbsp;Muzna Munir,&nbsp;Hassaan Anwer Rathore","doi":"10.1155/2022/7360782","DOIUrl":"10.1155/2022/7360782","url":null,"abstract":"<div>\u0000 <p>Rheumatoid arthritis (RA) is a systemic inflammatory disorder that can cause destructive joint disease, significant disability, and increased mortality. RA is the most frequent of all chronic inflammatory joint diseases, and its prevalence frequency in Pakistan is 1.6 per thousand people. Different cytokines and receptors were involved in the triggering of RA, including interleukin-6 (ILR-6), major histocompatibility complex (MHC) antigen human leukocyte (HLA-DR) receptor, and CD20. Several studies illustrated RA as an inherent immune response and triggered due to the “shared epitope.” Therefore, the involvement of all these receptors (IL-6, HLA-DR, and CD20) leads to the neurological, ocular, respiratory, cardiac, skin, and hematological manifestations that have been considered a potential therapeutic target for drug design. Various herbal, natural, and synthetic source inhibitors of interleukin-6 (IL-6), human leukocyte (HLA-DR), and CD20 were studied and reported previously. Reported inhibitors are compared to elucidate the best inhibitor for clinical trials, leading to the orally active drug. In this study, a computer-aided drug designing approach disclosed the potential inhibitors for all receptors based on their distinct binding affinity. Moreover, drug suitability was carried out using Lipinski’s rule by considering the adsorption, distribution, metabolism, and excretion (ADME) of ligands. Results elucidated “calycosin 7-O-glucoside” and “angeliferulate” as putative ligands for IL-6 and HLA-DR, respectively. However, the pharmacokinetic properties (ADMET) revealed angeliferulate as an effete ligand for the biological system compared to calycosin 7-O-glucoside. Based on docking, drug toxicity profiling or pharmacokinetics, and MD simulation stability, this study highlights orally active therapeutic inhibitors to inhibit the activity of pivotal receptors (IL6, HLA-DR, and CD20) of RA in humans. After clinical trials, the resultant inhibitors could be potential therapeutic agents in the drug development against RA.</p>\u0000 </div>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"2022 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2022-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2022/7360782","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45537841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Model of Intracellular Persistence of Pseudomonas aeruginosa in Airway Epithelial Cells","authors":"Julien K. Malet,&nbsp;Lisa C. Hennemann,&nbsp;Elizabeth M.-L. Hua,&nbsp;Emmanuel Faure,&nbsp;Valerie Waters,&nbsp;Simon Rousseau,&nbsp;Dao Nguyen","doi":"10.1155/2022/5431666","DOIUrl":"10.1155/2022/5431666","url":null,"abstract":"<div>\u0000 <p><i>Pseudomonas aeruginosa</i> (<i>P.a.</i>) is a major human pathogen capable of causing chronic infections in hosts with weakened barrier functions and host defenses, most notably airway infections commonly observed in individuals with the genetic disorder cystic fibrosis (CF). While mainly described as an extracellular pathogen, previous <i>in vitro</i> studies have described the molecular events leading to <i>P.a.</i> internalization in diverse epithelial cell types. However, the long-term fate of intracellular <i>P.a.</i> remains largely unknown. Here, we developed a model allowing for a better understanding of long-term (up to 120 h) intracellular bacterial survival in the airway epithelial cell line BEAS-2B. Using a tobramycin protection assay, we characterized the internalization, long-term intracellular survival, and cytotoxicity of the lab strain PAO1, as well as clinical CF isolates, and conducted analyses at the single-cell level using confocal microscopy and flow cytometry techniques. We observed that infection at low multiplicity of infection allows for intracellular survival up to 120 h post-infection without causing significant host cytotoxicity. Finally, infection with clinical isolates revealed significant strain-to-strain heterogeneity in intracellular survival, including a high persistence phenotype associated with bacterial replication within host cells. Future studies using this model will further elucidate the host and bacterial mechanisms that promote <i>P. aeruginosa</i> intracellular persistence in airway epithelial cells, a potentially unrecognized bacterial reservoir during chronic infections.</p>\u0000 </div>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"2022 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2022-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2022/5431666","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46567110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}