Cellular Microbiology最新文献

{"title":"Host manipulation by bacterial type III and type IV secretion system effector proteases","authors":"Flávia Viana,&nbsp;Shruthi Sachidanandan Peringathara,&nbsp;Arshad Rizvi,&nbsp;Gunnar N. Schroeder","doi":"10.1111/cmi.13384","DOIUrl":"10.1111/cmi.13384","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Proteases are powerful enzymes, which cleave peptide bonds, leading most of the time to irreversible fragmentation or degradation of their substrates. Therefore they control many critical cell fate decisions in eukaryotes. Bacterial pathogens exploit this power and deliver protease effectors through specialised secretion systems into host cells. Research over the past years revealed that the functions of protease effectors during infection are diverse, reflecting the lifestyles and adaptations to specific hosts; however, only a small number of peptidase families seem to have given rise to most of these protease virulence factors by the evolution of different substrate-binding specificities, intracellular activation and subcellular targeting mechanisms. Here, we review our current knowledge about the enzymology and function of protease effectors, which Gram-negative bacterial pathogens translocate via type III and IV secretion systems to irreversibly manipulate host processes. We highlight emerging concepts such as signalling by protease cleavage products and effector-triggered immunity, which host cells employ to detect and defend themselves against a protease attack.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Take Away</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Proteases irreversibly cleave proteins to control critical cell fate decisions.</li>\u0000 \u0000 <li>Gram-negative bacteria use type III and IV secretion systems to inject effectors.</li>\u0000 \u0000 <li>Protease effectors are integral weapons for the manipulation of host processes.</li>\u0000 \u0000 <li>Effectors evolved from few peptidase families to target diverse substrates.</li>\u0000 \u0000 <li>Effector-triggered immunity upon proteolytic attack emerges as host defence.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 11","pages":""},"PeriodicalIF":3.4,"publicationDate":"2021-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/cmi.13384","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39311101","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":"Mucosal immune responses in the trachea after chronic infection with Mycoplasma gallisepticum in unvaccinated and vaccinated mature chickens","authors":"Sathya N. Kulappu Arachchige,&nbsp;Nadeeka K. Wawegama,&nbsp;Mauricio J. C. Coppo,&nbsp;Habtamu B. Derseh,&nbsp;Paola K. Vaz,&nbsp;Anna Kanci Condello,&nbsp;Oluwadamilola S. Omotainse,&nbsp;Amir H. Noormohammadi,&nbsp;Glenn F. Browning","doi":"10.1111/cmi.13383","DOIUrl":"10.1111/cmi.13383","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;p&gt;Tracheitis associated with the chronic respiratory disease in chickens caused by &lt;i&gt;Mycoplasma gallisepticum&lt;/i&gt; is marked by infiltration of leukocytes into the mucosa. Although cytokines/chemokines are known to play a key role in the recruitment, differentiation, and proliferation of leukocytes, those that are produced and secreted into the trachea during the chronic stages of infection with &lt;i&gt;M. gallisepticum&lt;/i&gt; have not been described previously. In this study, the levels of transcription in the trachea of genes encoding a panel of 13 cytokines/chemokines were quantified after experimental infection with the &lt;i&gt;M. gallisepticum&lt;/i&gt; wild-type strain Ap3AS in unvaccinated chickens and chickens vaccinated 40-, 48- or 57-weeks previously with the novel attenuated strain ts-304. These transcriptional levels in unvaccinated/infected and vaccinated/infected chickens were compared with those of unvaccinated/uninfected and vaccinated/uninfected chickens. Pathological changes and subsets of leukocytes infiltrating the tracheal mucosa were concurrently assessed by histopathological examination and indirect immunofluorescent staining. After infection, unvaccinated birds had a significant increase in tracheal mucosal thickness and in transcription of genes for cytokines/chemokines, including those for IFN-γ, IL-17, RANTES (CCLi4), and CXCL-14, and significant downregulation of IL-2 gene transcription. B cells, CD3&lt;sup&gt;+&lt;/sup&gt; or CD4&lt;sup&gt;+&lt;/sup&gt; cells and macrophages (KUL01&lt;sup&gt;+&lt;/sup&gt;) accumulated in the mucosa but CD8&lt;sup&gt;+&lt;/sup&gt; cells were not detected. In vaccinated birds, the levels of transcription of the genes for IL-6, IL-2, RANTES and CXCL-14 were significantly lower after infection than in the unvaccinated/infected and/or unvaccinated/uninfected birds, while the transcription of the IFN-γ gene was significantly upregulated, and there were aggregations of B cells in the tracheal mucosa. These observations indicated that &lt;i&gt;M. gallisepticum&lt;/i&gt; may have suppressed Th2 responses by upregulating secretion of IFN-γ and IL-17 by CD4&lt;sup&gt;+&lt;/sup&gt; cells and induced immune dysregulation characterized by depletion of CD8&lt;sup&gt;+&lt;/sup&gt; cells and downregulation of IL-2 in the tracheas of unvaccinated birds. The ts-304 vaccine appeared to induce long-term protection against this immune dysregulation.&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;The ts-304 vaccine-induced long-term protection against immune dysregulation caused by &lt;i&gt;M. gallisepticum&lt;/i&gt;&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Detection of B cells and plasma cells in the tracheal mucosa suggested that long-term protection is mediated by mucosal B cell memory&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Infection of","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 11","pages":""},"PeriodicalIF":3.4,"publicationDate":"2021-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/cmi.13383","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39271613","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":"Feminising Wolbachia disrupt Armadillidium vulgare insulin-like signalling pathway","authors":"Benjamin Herran,&nbsp;Camille Houdelet,&nbsp;Maryline Raimond,&nbsp;Carine Delaunay,&nbsp;Nicolas Cerveau,&nbsp;Catherine Debenest,&nbsp;Pierre Grève,&nbsp;Joanne Bertaux","doi":"10.1111/cmi.13381","DOIUrl":"10.1111/cmi.13381","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>The endosymbiont <i>Wolbachia</i> feminises male isopods by making them refractory to the insulin-like masculinising hormone, which shunts the autocrine development of the androgenic glands. It was, therefore, proposed that <i>Wolbachia</i> silences the IR receptors, either by preventing their expression or by inactivating them. We describe here the two IR paralogs of <i>Armadillidium vulgare</i>. They displayed a conventional structure and belonged to a family widespread among isopods. Av-IR1 displayed an ubiquist expression, whereas the expression of Av-IR2 was restricted to the gonads. Both were constitutively expressed in males and females and throughout development. However, upon silencing, altered gland physiology and gene expression therein suggested antagonistic roles for Av-IR1 (androinhibiting) and Av-IR2 (androstimulating). They may function in tandem with regulating neurohormones, as a conditional platform that conveys insulin signalling. <i>Wolbachia</i> infection did not alter their expression patterns: leaving the IRs unscathed, the bacteria would suppress the secretion of the neurohormones, thus inducing body-wide IR deactivation and feminisation. Adult males injected with <i>Wolbachia</i> acquired an intersexed physiology. Their phenotypes and gene expressions mirrored the silencing of Av-IR1 only, suggesting that imperfect feminisation stems from a flawed invasion of the androstimulating centre, whereas in fully feminised males invasion would be complete in early juveniles.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Take Away</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Two antagonistic Insulin Receptors were characterised in <i>Armadillidium vulgare</i>.</li>\u0000 \u0000 <li>The IRs were involved in androstimulating and androinhibiting functions.</li>\u0000 \u0000 <li><i>Wolbachia</i>-induced feminisation did not prevent the expression of the IRs.</li>\u0000 \u0000 <li>Imperfectly feminised intersexes phenocopied the silencing of Av-IR1 only.</li>\u0000 \u0000 <li><i>Wolbachia</i> would deactivate the IRs by suppressing neurosecretory co-factors.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 11","pages":""},"PeriodicalIF":3.4,"publicationDate":"2021-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/cmi.13381","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39225678","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":"Endocytosis of the CdtA subunit from the Haemophilus ducreyi cytolethal distending toxin","authors":"G. Robb Huhn III,&nbsp;Naly Torres-Mangual,&nbsp;John Clore,&nbsp;Lucia Cilenti,&nbsp;Teresa Frisan,&nbsp;Ken Teter","doi":"10.1111/cmi.13380","DOIUrl":"10.1111/cmi.13380","url":null,"abstract":"Many Gram‐negative pathogens produce a cytolethal distending toxin (CDT) with two cell‐binding subunits (CdtA + CdtC) and a catalytic CdtB subunit. After adhesion to the plasma membrane of a target cell, CDT moves by retrograde transport to endoplasmic reticulum. CdtB then enters the nucleus where it generates DNA breaks that lead to cell cycle arrest and apoptosis or senescence. CdtA anchors the CDT holotoxin to the plasma membrane and is thought to remain on the cell surface after endocytosis of the CdtB/CdtC heterodimer. Here, we re‐examined the potential endocytosis and intracellular transport of CdtA from the Haemophilus ducreyi CDT. We recorded the endocytosis of holotoxin‐associated CdtA with a cell‐based enzyme‐linked immunoabsorbent assay (CELISA) and visualised its presence in the early endosomes by confocal microscopy 10 min after CDT binding to the cell surface. Western blot analysis documented the rapid degradation of internalised CdtA. Most of internalised CdtB and CdtC were degraded as well. The rapid rate of CDT internalisation and turnover, which could explain why CdtA endocytosis was not detected in previous studies, suggests only a minor pool of cell‐associated CdtB reaches the nucleus. Our work demonstrates that CDT is internalised as an intact holotoxin and identifies the endosomes as the site of CdtA dissociation from CdtB/CdtC.","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 11","pages":""},"PeriodicalIF":3.4,"publicationDate":"2021-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/cmi.13380","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39208259","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":"Hepatitis E virus egress and beyond – the manifold roles of the viral ORF3 protein","authors":"Mirco Glitscher,&nbsp;Eberhard Hildt","doi":"10.1111/cmi.13379","DOIUrl":"10.1111/cmi.13379","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Although the hepatitis E virus represents an uprising threat to the global community by representing the commonest cause of an acute viral hepatitis worldwide, its life cycle is grossly understudied. Albeit HEV is a non-enveloped virus, its progeny is released as quasi-enveloped virions. Thus, the responsible accessory protein pORF3 gained rising attention in the past years. It mediates viral release via the exosomal route by targeting the viral capsid to the endosomal system, more precisely to multivesicular bodies. As this is followed by quasi-envelopment, pORF3 may in terms represent a substitute to a conventional envelope protein. This feature proofs to be rather unique with respect to other enteric viruses, although the protein's role in the viral life cycle seems to reach far beyond simply maintaining release of progeny viruses. How pORF3 affects viral morphogenesis, how it mediates efficient viral release and how it supports viral spread is summarised in this microreview. With this, we aim to shed light on functions of pORF3 to gain further insights in still enigmatic aspects of the HEV life cycle.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Take Aways</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>HEV is released as exosome via multivesicular bodies</li>\u0000 \u0000 <li>Viral pORF3 mediates release via endosomal complexes required for transport</li>\u0000 \u0000 <li>pORF3 modulates various cellular processes in infected cells</li>\u0000 \u0000 <li>Elucidation of pORF3-related processes imply novel clinical strategies</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 12","pages":""},"PeriodicalIF":3.4,"publicationDate":"2021-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/cmi.13379","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39192540","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":"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}