Cellular Microbiology最新文献

{"title":"Cover Image: Salmonella Typhimurium manipulates macrophage cholesterol homeostasis through the SseJ-mediated suppression of the host cholesterol transport protein ABCA1 (Cellular Microbiology 08/2021)","authors":"Adam R. Greene,&nbsp;Katherine A. Owen,&nbsp;James E. Casanova","doi":"10.1111/cmi.13377","DOIUrl":"10.1111/cmi.13377","url":null,"abstract":"<p><i>Salmonella</i> Typhimurium induces accumulation of cholesterol in WT macrophages (top right) but not in the absence of the host kinase FAK (bottom left) or the bacterial effector protein SseJ (bottom right). For further details, readers are referred to the article by Greene et al. on p. e13329 of this issue.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 8","pages":""},"PeriodicalIF":3.4,"publicationDate":"2021-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/cmi.13377","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46928012","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":"Candidalysin delivery to the invasion pocket is critical for host epithelial damage induced by Candida albicans","authors":"Selene Mogavero,&nbsp;Frank M. Sauer,&nbsp;Sascha Brunke,&nbsp;Stefanie Allert,&nbsp;Daniela Schulz,&nbsp;Stephanie Wisgott,&nbsp;Nadja Jablonowski,&nbsp;Osama Elshafee,&nbsp;Thomas Krüger,&nbsp;Olaf Kniemeyer,&nbsp;Axel A. Brakhage,&nbsp;Julian R. Naglik,&nbsp;Edward Dolk,&nbsp;Bernhard Hube","doi":"10.1111/cmi.13378","DOIUrl":"10.1111/cmi.13378","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>The human pathogenic fungus <i>Candida albicans</i> is a frequent cause of mucosal infections. Although the ability to transition from the yeast to the hypha morphology is essential for virulence, hypha formation and host cell invasion per se are not sufficient for the induction of epithelial damage. Rather, the hypha-associated peptide toxin, candidalysin, a product of the Ece1 polyprotein, is the critical damaging factor. While synthetic, exogenously added candidalysin is sufficient to damage epithelial cells, the level of damage does not reach the same level as invading <i>C. albicans</i> hyphae. Therefore, we hypothesized that a combination of fungal attributes is required to deliver candidalysin to the invasion pocket to enable the full damaging potential of <i>C. albicans</i> during infection. Utilising a panel of <i>C. albicans</i> mutants with known virulence defects, we demonstrate that the full damage potential of <i>C. albicans</i> requires the coordinated delivery of candidalysin to the invasion pocket. This process requires appropriate epithelial adhesion, hyphal extension and invasion, high levels of <i>ECE1</i> transcription, proper Ece1 processing and secretion of candidalysin. To confirm candidalysin delivery, we generated camelid V_HHs (nanobodies) specific for candidalysin and demonstrate localization and accumulation of the toxin only in <i>C. albicans</i>-induced invasion pockets. In summary, a defined combination of virulence attributes and cellular processes is critical for delivering candidalysin to the invasion pocket to enable the full damage potential of <i>C. albicans</i> during mucosal infection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Take Aways</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Candidalysin is a peptide toxin secreted by <i>C. albicans</i> causing epithelial damage.</li>\u0000 \u0000 <li>Candidalysin delivery to host cell membranes requires specific fungal attributes.</li>\u0000 \u0000 <li>Candidalysin accumulates in invasion pockets created by invasive hyphae.</li>\u0000 \u0000 <li>Camelid nanobodies enabled visualisation of candidalysin in the invasion pocket.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2021-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/cmi.13378","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39170567","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":"The Helicobacter pylori type IV secretion system upregulates epithelial cortactin expression by a CagA- and JNK-dependent pathway","authors":"Irshad Sharafutdinov,&nbsp;Steffen Backert,&nbsp;Nicole Tegtmeyer","doi":"10.1111/cmi.13376","DOIUrl":"10.1111/cmi.13376","url":null,"abstract":"Cortactin represents an important actin‐binding factor, which controls actin‐cytoskeletal remodelling in host cells. In this way, cortactin has been shown to exhibit crucial functions both for cell movement and tumour cell invasion. In addition, the cortactin gene cttn is amplified in various cancer types of humans. Helicobacter pylori is the causative agent of multiple gastric diseases and represents a significant risk factor for the development of gastric adenocarcinoma. It has been repeatedly shown that H. pylori manipulates cancer‐related signal transduction events in infected gastric epithelial cells such as the phosphorylation status of cortactin. In fact, H. pylori modifies the activity of cortactin's binding partners to stimulate changes in the actin‐cytoskeleton, cell adhesion and motility. Here we show that H. pylori infection of cultured AGS and Caco‐2 cells for 24–48 hr leads to the overexpression of cortactin by 2–3 fold at the protein level. We demonstrate that this activity requires the integrity of the type IV secretion system (T4SS) encoded by the cag pathogenicity island (cagPAI) as well as the translocated effector protein CagA. We further show that ectopic expression of CagA is sufficient to stimulate cortactin overexpression. Furthermore, phosphorylation of CagA at the EPIYA‐repeat region is not required, suggesting that this CagA activity proceeds in a phosphorylation‐independent fashion. Inhibitor studies further demonstrate that the involved signalling pathway comprises the mitogen‐activated protein kinase JNK (c‐Jun N‐terminal kinase), but not ERK1/2 or p38. Taken together, using H. pylori as a model system, this study discovered a previously unrecognised cortactin activation cascade by a microbial pathogen. We suggest that H. pylori targets cortactin to manipulate the cellular architecture and epithelial barrier functions that can impact gastric cancer development.","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/cmi.13376","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39129710","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":"Galectin-3 regulates proinflammatory cytokine function and favours Brucella abortus chronic replication in macrophages and mice","authors":"Fernanda L. Tana,&nbsp;Erika S. Guimarães,&nbsp;Daiane M. Cerqueira,&nbsp;Priscila C. Campos,&nbsp;Marco Túlio R. Gomes,&nbsp;Fábio V. Marinho,&nbsp;Sergio C. Oliveira","doi":"10.1111/cmi.13375","DOIUrl":"10.1111/cmi.13375","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>In this study, we provide evidence that galectin-3 (Gal-3) plays an important role in <i>Brucella abortus</i> infection. Our results showed increased Gal-3 expression and secretion in <i>B. abortus</i> infected macrophages and mice. Additionally, our findings indicate that Gal-3 is dispensable for <i>Brucella</i>-containing vacuoles disruption, inflammasome activation and pyroptosis. On the other hand, we observed that <i>Brucella</i>-induced Gal-3 expression is crucial for induction of molecules associated to type I IFN signalling pathway, such as IFN-β: Interferon beta (IFN-β), C-X-C motif chemokine ligand 10 (CXCL10) and guanylate-binding proteins. Gal-3 KO macrophages showed reduced bacterial numbers compared to wild-type cells, suggesting that Gal-3 facilitates bacterial replication in vitro. Moreover, priming Gal-3 KO cells with IFN-β favoured <i>B. abortus</i> survival in macrophages. Additionally, we also observed that Gal-3 KO mice are more resistant to <i>B. abortus</i> infection and these animals showed elevated production of proinflammatory cytokines when compared to control mice. Finally, we observed an increased recruitment of macrophages, dendritic cells and neutrophils in spleens of Gal-3 KO mice compared to wild-type animals. In conclusion, this study demonstrated that <i>Brucella</i>-induced Gal-3 is detrimental to host and this molecule is implicated in inhibition of recruitment and activation of immune cells, which promotes <i>B. abortus</i> spread and aggravates the infection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Take Aways</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li><i>Brucella abortus</i> infection upregulates galectin-3 expression</li>\u0000 \u0000 <li>Galectin-3 regulates guanylate-binding proteins expression but is not required for <i>Brucella</i>-containing vacuole disruption</li>\u0000 \u0000 <li>Galectin-3 modulates proinflammatory cytokine production during bacterial infection</li>\u0000 \u0000 <li>Galectin-3 favours <i>Brucella</i> replication</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2021-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/cmi.13375","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39105786","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":"Single-cell analyses reveal phosphate availability as critical factor for nutrition of Salmonella enterica within mammalian host cells","authors":"Jennifer Röder,&nbsp;Pascal Felgner,&nbsp;Michael Hensel","doi":"10.1111/cmi.13374","DOIUrl":"10.1111/cmi.13374","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;p&gt;&lt;i&gt;Salmonella enterica&lt;/i&gt; serovar Typhimurium (STM) is an invasive, facultative intracellular pathogen and acquisition of nutrients from host cells is essential for survival and proliferation of intracellular STM. The nutritional environment of intracellular STM is only partially understood. We deploy bacteria harbouring reporter plasmids to interrogate the environmental cues acting on intracellular STM, and flow cytometry allows analyses on level of single STM. Phosphorus is a macro-element for cellular life, and in STM inorganic phosphate (P&lt;sub&gt;i&lt;/sub&gt;), homeostasis is mediated by the two-component regulatory system PhoBR, resulting in expression of the high affinity phosphate transporter &lt;i&gt;pstSCAB-phoU&lt;/i&gt;. Using fluorescent protein reporters, we investigated P&lt;sub&gt;i&lt;/sub&gt; availability for intracellular STM at single-cell level over time. We observed that P&lt;sub&gt;i&lt;/sub&gt; concentration in the &lt;i&gt;Salmonella&lt;/i&gt;-containing vacuole (SCV) is limiting and activates the promoter of &lt;i&gt;pstSCAB-phoU&lt;/i&gt; encoding a high affinity phosphate uptake system. Correlation between reporter activation by STM in defined media and in host cells indicates P&lt;sub&gt;i&lt;/sub&gt; concentration less 10 μM within the SCV. STM proliferating within the SCV experience increasing P&lt;sub&gt;i&lt;/sub&gt; limitations. Activity of the &lt;i&gt;Salmonella&lt;/i&gt; pathogenicity island 2 (SPI2)-encoded type III secretion system (T3SS) is crucial for efficient intracellular proliferation, and SPI2-T3SS-mediated endosomal remodelling also reliefs P&lt;sub&gt;i&lt;/sub&gt; limitation. STM that are released from SCV to enter the cytosol of epithelial cells did not indicate P&lt;sub&gt;i&lt;/sub&gt; limitations. Addition of P&lt;sub&gt;i&lt;/sub&gt; to culture media of infected cells partially relieved P&lt;sub&gt;i&lt;/sub&gt; limitations in the SCV, as did inhibition of intracellular proliferation. We conclude that availability of P&lt;sub&gt;i&lt;/sub&gt; is critical for intracellular lifestyle of STM, and P&lt;sub&gt;i&lt;/sub&gt; acquisition is maintained by multiple mechanisms. Our work demonstrates the use of bacterial pathogens as sensitive single-cell reporters for their environment in host cell or host organisms.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Take Away&lt;/h3&gt;\u0000 \u0000 &lt;div&gt;\u0000 &lt;ul&gt;\u0000 \u0000 &lt;li&gt;&lt;i&gt;Salmonella&lt;/i&gt; strains were engineered to report their intracellular niche and the availability of inorganic phosphate (P&lt;sub&gt;i&lt;/sub&gt;) on level of single intracellular bacteria&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Within the &lt;i&gt;Salmonella&lt;/i&gt;-containing vacuole (SCV), P&lt;sub&gt;i&lt;/sub&gt; is limited and limitation increases with bacterial proliferation&lt;/li&gt;\u0000 \u0000 &lt;li&gt;&lt;i&gt;Salmonella&lt;/i&gt; located in host cell cytosol are not limited in P&lt;sub&gt;i&lt;/sub&gt; availability&lt;/li&gt;\u0000 \u0000 &lt;li&gt;R","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2021-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/cmi.13374","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39098982","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":"Emerging methods in cellular microbiology","authors":"Elizabeth L. Hartland","doi":"10.1111/cmi.13369","DOIUrl":"10.1111/cmi.13369","url":null,"abstract":"<p>In an era where new viruses can emerge suddenly and anti-microbial resistance is now widespread, a full understanding of the pathogen and host factors that contribute to disease pathology and spread remains a critically important goal. Methods and technologies to study the cell biology of infection are changing rapidly. The interdisciplinary requirements to interrogate host-pathogen interactions are ever more complex and indispensable to identify the cellular and immune factors that lead to the resolution of infection. The ability of a pathogen to replicate in the host likewise needs a thorough knowledge of the pathogen determinants required to cause disease. In this special issue, <i>Cellular Microbiology</i> highlights some of the most cutting-edge approaches and techniques to study pathogen biology and infection.</p><p>Light based and electron microscopic imaging has long played an important role in defining the intracellular mechanisms of infection. Such methods can now be quickly adapted through the design of fluorescent reporters and utilised for high throughout applications. Cortese and Laketa <span>(2021)</span> describe recent advances in high-throughput microscopy and electron microscopy and explain how these were applied during the SARS-CoV-2 outbreak (Cortese &amp; Laketa, <span>2021</span>). For example, the development of a mNeonGreen reporter microscopy-based virus neutralisation assay outperformed standard plaque assays in sensitivity and time in the critical early stages of the COVID-19 pandemic (Muruato et al., <span>2020</span>). Cryo-electron microscopy was instrumental in rapidly defining the structure of the SARS-CoV-2 spike protein in complex with its cellular receptor, angiotensin convertase enzyme 2 (ACE2), directly informing an understanding of neutralising antibodies (Cortese &amp; Laketa, <span>2021</span>). In bacterial pathogens, Dufrêne, Viljoen, Mignolet, and Mathelié-Guinlet (<span>2021</span>) report on the utility of atomic force microscopy (AFM) to provide super-resolution imaging and nanomechanical measurements of bacterial cell surfaces and receptor-ligand interactions. This is providing new insight into the fine structure and biophysical function of adhesins and also informing vaccine and drug development (Dufrêne et al., <span>2021</span>).</p><p>The subcellular host cell compartment occupied by intracellular pathogens is highly specialised to support pathogen replication. Given their role in sampling of extracellular fluid, macropinosomes are hijacked by diverse pathogens to establish entry into the intracellular environment. However, macropinosomes are also highly dynamic organelles with a range of cellular functions. Chang, Enninga, and Stévenin <span>(2021)</span> describe imaging-based and proteomic methods for the tracking and characterisation of these important organelles as they are modified as a niche for invasion and/or replication by bacteria such as <i>Shigella</i>, <i>Salmonella</i>, <i>Bruc","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2021-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/cmi.13369","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39099817","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":"Syncollin is an antibacterial polypeptide","authors":"Rosie A. Waters,&nbsp;James Robinson,&nbsp;J. Michael Edwardson","doi":"10.1111/cmi.13372","DOIUrl":"10.1111/cmi.13372","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Syncollin is a 16-kDa protein found predominantly in the zymogen granules of pancreatic acinar cells, with expression at lower levels in intestinal epithelial cells and neutrophils. Here, we used Strep-tagged syncollin isolated from the supernatant of transiently transfected mammalian cells to test the hypothesis that syncollin has antibacterial properties, which might enable it to play a role in host defence in the gut and possibly elsewhere. We show that syncollin is an exceptionally thermostable protein with a circular dichroism spectrum consistent with a predominantly beta-sheet structure. Syncollin binds to bacterial peptidoglycan and restricts the growth of representative Gram-positive (<i>Lactococcus lactis</i>) and Gram-negative (<i>Escherichia coli</i>) bacteria. Syncollin induces propidium iodide uptake into <i>E. coli</i> (but not <i>L. lactis</i>), indicating permeabilisation of the bacterial membrane. It also causes surface structural damage in both <i>L. lactis</i> and <i>E. coli</i>, as visualised by scanning electron microscopy. We propose that syncollin is a previously unidentified member of a large group of antimicrobial polypeptides that control the gut microbiome.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Take Aways</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Syncollin is a 16-kDa protein found in pancreatic zymogen granules.</li>\u0000 \u0000 <li>Syncollin is highly thermostable and has a predominantly beta-sheet structure.</li>\u0000 \u0000 <li>Syncollin binds peptidoglycan and restricts the growth of <i>L. lactis</i> and <i>E. coli</i>.</li>\u0000 \u0000 <li>Syncollin causes propidium iodide uptake into <i>E. coli</i> (but not <i>L. lactis</i>).</li>\u0000 \u0000 <li>Syncollin causes surface structural damage in both <i>L. lactis</i> and <i>E. coli</i>.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2021-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/cmi.13372","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39258157","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":"Inflammasome activation and IL-1β signalling in group A Streptococcus disease","authors":"Johanna Richter,&nbsp;Stephan Brouwer,&nbsp;Kate Schroder,&nbsp;Mark J. Walker","doi":"10.1111/cmi.13373","DOIUrl":"10.1111/cmi.13373","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Group A <i>Streptococcus</i> (GAS) is a Gram-positive bacterial pathogen that causes significant morbidity and mortality worldwide. Recent clinical evidence suggests that the inflammatory marker interleukin-1β (IL-1β) plays an important role in GAS disease progression, and presents a potential target for therapeutic intervention. Interaction with GAS activates the host inflammasome pathway to stimulate production and secretion of IL-1β, but GAS can also stimulate IL-1β production in an inflammasome-independent manner. This review highlights progress that has been made in understanding the importance of host cell inflammasomes and IL-1 signalling in GAS disease, and explores challenges and unsolved problems in this host-pathogen interaction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Take Away</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Inflammasome signalling during GAS infection is an emerging field of research.</li>\u0000 \u0000 <li>GAS modulates the NLRP3 inflammasome pathway through multiple mechanisms.</li>\u0000 \u0000 <li>SpeB contributes to IL-1β production independently of the inflammasome pathway.</li>\u0000 \u0000 <li>IL-1β signalling can be host-protective, but also drive severe GAS disease.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 9","pages":""},"PeriodicalIF":3.4,"publicationDate":"2021-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/cmi.13373","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39095839","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 putative PKA phosphorylation site S227 in MoSom1 is essential for infection-related morphogenesis and pathogenicity in Magnaporthe oryzae","authors":"Shuzhen Deng,&nbsp;Lin Xu,&nbsp;Zhe Xu,&nbsp;Wuyun Lv,&nbsp;Zhengxian Chen,&nbsp;Nan Yang,&nbsp;Nicholas J. Talbot,&nbsp;Zhengyi Wang","doi":"10.1111/cmi.13370","DOIUrl":"10.1111/cmi.13370","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>In the rice blast fungus <i>Magnaporthe oryzae</i>, the cAMP signalling pathway plays a critical role in regulating leaf surface recognition and the initiation of appressorium development. Direct downstream targets of the cAMP signalling pathway are, however, not well-characterised. The MoSom1 protein functions downstream of the cAMP dependent protein kinase A (cAMP-PKA) and is essential for infection-related morphogenesis and pathogenicity. In this study, we show that mutation of a putative PKA phosphorylation site in MoSom1 is essential for its role in appressorium differentiation and pathogenicity in <i>M. oryzae</i>. Mutation of serine 227 in MoSom1 by deletion or serine (S) substitution to alanine (A), valine (V) or tyrosine (Y), resulted in defects of conidiation, appressorium-like structure formation and fungal pathogenicity. Western blot analysis confirmed that S227 in MoSom1 is a putative PKA phosphorylation site. Furthermore, a <i>ΔMosom1</i> mutant showed reduced expression of <i>PMK1</i> and was defective in Pmk1 phosphorylation, indicating that the Pmk1 mitogen-activated protein kinase (MAPK) acts downstream of MoSom1 in <i>M. oryzae</i>. We conclude that the cAMP-PKA pathway may regulate the Pmk1 MAPK pathway through MoSom1 during rice infection by the blast fungus.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Take Aways</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>S227 is crucial for MoSom1 function in <i>M. oryzae</i>.</li>\u0000 \u0000 <li>S227 in MoSom1 was identified as a putative PKA phosphorylation site in <i>M. oryzae</i>.</li>\u0000 \u0000 <li>S227 is essential for infection-related morphogenesis and pathogenicity in <i>M. oryzae</i>.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2021-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/cmi.13370","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39064388","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":"Candidalysin triggers epithelial cellular stresses that induce necrotic death","authors":"Mariana Blagojevic,&nbsp;Giorgio Camilli,&nbsp;Michelle Maxson,&nbsp;Bernhard Hube,&nbsp;David L. Moyes,&nbsp;Jonathan P. Richardson,&nbsp;Julian R. Naglik","doi":"10.1111/cmi.13371","DOIUrl":"10.1111/cmi.13371","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p><i>Candida albicans</i> is a common opportunistic fungal pathogen that causes a wide range of infections from superficial mucosal to hematogenously disseminated candidiasis. The hyphal form plays an important role in the pathogenic process by invading epithelial cells and causing tissue damage. Notably, the secretion of the hyphal toxin candidalysin is essential for both epithelial cell damage and activation of mucosal immune responses. However, the mechanism of candidalysin-induced cell death remains unclear. Here, we examined the induction of cell death by candidalysin in oral epithelial cells. Fluorescent imaging using healthy/apoptotic/necrotic cell markers revealed that candidalysin causes a rapid and marked increase in the population of necrotic rather than apoptotic cells in a concentration dependent manner. Activation of a necrosis-like pathway was confirmed since <i>C. albicans</i> and candidalysin failed to activate caspase-8 and -3, or the cleavage of poly (ADP-ribose) polymerase. Furthermore, oral epithelial cells treated with candidalysin showed rapid production of reactive oxygen species, disruption of mitochondria activity and mitochondrial membrane potential, ATP depletion and cytochrome c release. Collectively, these data demonstrate that oral epithelial cells respond to the secreted fungal toxin candidalysin by triggering numerous cellular stress responses that induce necrotic death.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Take aways</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Candidalysin secreted from <i>Candida albicans</i> causes epithelial cell stress.</li>\u0000 \u0000 <li>Candidalysin induces calcium influx and oxidative stress in host cells.</li>\u0000 \u0000 <li>Candidalysin induces mitochondrial dysfunction, ATP depletion and epithelial necrosis.</li>\u0000 \u0000 <li>The toxicity of candidalysin is mediated from the epithelial cell surface.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2021-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/cmi.13371","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39076404","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}