Cellular Microbiology最新文献

{"title":"Type III secreted effectors that target mitochondria","authors":"Ipsita Nandi,&nbsp;Lior Aroeti,&nbsp;Rachana Pattani Ramachandran,&nbsp;Ephrem G. Kassa,&nbsp;Efrat Zlotkin-Rivkin,&nbsp;Benjamin Aroeti","doi":"10.1111/cmi.13352","DOIUrl":"10.1111/cmi.13352","url":null,"abstract":"<p>A type III secretion system (T3SS) is used by Gram-negative bacterial pathogens to secrete and translocate a battery of proteins, termed effectors, from the bacteria directly into the host cells. These effectors, which are thought to play a key role in bacterial virulence, hijack and modify the activity of diverse host cell organelles, including mitochondria. Mitochondria—the energy powerhouse of the cell—are important cell organelles that play role in numerous critical cellular processes, including the initiation of apoptosis and the induction of innate immunity. Therefore, it is not surprising that pathogenic bacteria use mitochondrially targeted effectors to control host cell death and immunity pathways. Surprisingly, however, we found that despite their importance, only a limited number of type III secreted effectors have been characterised to target host mitochondria, and the mechanisms underlying their mitochondrial activity have not been sufficiently analysed. These include effectors secreted by the enteric attaching and effacing (A/E), <i>Salmonella</i> and <i>Shigella</i> bacterial pathogens. Here we give an overview of key findings, present gaps in knowledge and hypotheses concerning the mode by which these type III secreted effectors control the host and the bacterial cell life (and death) through targeting mitochondria.</p>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 9","pages":""},"PeriodicalIF":3.4,"publicationDate":"2021-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/cmi.13352","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38968609","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":"Pathogenesis of Borrelia burgdorferi and Babesia microti in TLR4-Competent and TLR4-dysfunctional C3H mice","authors":"Lavoisier Akoolo,&nbsp;Vitomir Djokic,&nbsp;Sandra C. Rocha,&nbsp;Nikhat Parveen","doi":"10.1111/cmi.13350","DOIUrl":"10.1111/cmi.13350","url":null,"abstract":"<p><i>Toll-like receptors</i> (TLRs) are a class of membrane-spanning <i>proteins of host cells</i>. TLR2 and TLR4 are displayed on the surface of macrophages, neutrophils and dendritic cells and recognise structurally conserved microbial signatures defined as Pathogen associated molecular patterns (PAMPs). C3H mice are susceptible to tick-borne pathogens; Lyme disease causing <i>Borrelia burgdorferi</i> that manifests arthritis and carditis and Apicomplexan protozoan, <i>Babesia microti</i> (<i>Bm</i>) that causes significant parasitemia associated with erythrocytopenia and haemoglobinuria. <i>B. burgdorferi</i> lacks typical TLR4 ligand lipopolysaccharides (LPS) and <i>Bm</i> TLR ligand(s) remain unknown. Only <i>Borrelia</i> lipoproteins that signal through TLR2 are established as PAMPs of these pathogens for TLR2/TLR4. Infection of C3H mice with each pathogen individually resulted in increase in the percentage of splenic B, T and FcR+ cells while their co-infection significantly diminished levels of these cells and caused increased <i>B. burgdorferi</i> burden in the specific organs. The most pronounced inflammatory arthritis was observed in co-infected C3H/HeJ mice. Parasitemia levels and kinetics of resolution of <i>Bm</i> in both mice strains were not significantly different. Transfected HEK293 cells showed pronounced signalling by <i>B. burgdorferi</i> through TLR2 and to some extent by TLR4 while <i>Bm</i> and infected erythrocytes did not show any response confirming our results in mice.</p>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 9","pages":""},"PeriodicalIF":3.4,"publicationDate":"2021-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/cmi.13350","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38941793","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":"HRMAn 2.0: Next-generation artificial intelligence–driven analysis for broad host–pathogen interactions","authors":"Daniel Fisch,&nbsp;Robert Evans,&nbsp;Barbara Clough,&nbsp;Sophie K. Byrne,&nbsp;Will M. Channell,&nbsp;Jacob Dockterman,&nbsp;Eva-Maria Frickel","doi":"10.1111/cmi.13349","DOIUrl":"10.1111/cmi.13349","url":null,"abstract":"<p>To study the dynamics of infection processes, it is common to manually enumerate imaging-based infection assays. However, manual counting of events from imaging data is biased, error-prone and a laborious task. We recently presented HRMAn (Host Response to Microbe Analysis), an automated image analysis program using state-of-the-art machine learning and artificial intelligence algorithms to analyse pathogen growth and host defence behaviour. With HRMAn, we can quantify intracellular infection by pathogens such as <i>Toxoplasma gondii</i> and <i>Salmonella</i> in a variety of cell types in an unbiased and highly reproducible manner, measuring multiple parameters including pathogen growth, pathogen killing and activation of host cell defences. Since HRMAn is based on the KNIME Analytics platform, it can easily be adapted to work with other pathogens and produce more readouts from quantitative imaging data. Here we showcase improvements to HRMAn resulting in the release of HRMAn 2.0 and new applications of HRMAn 2.0 for the analysis of host–pathogen interactions using the established pathogen <i>T. gondii</i> and further extend it for use with the bacterial pathogen <i>Chlamydia trachomatis</i> and the fungal pathogen <i>Cryptococcus neoformans</i>.</p>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2021-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/cmi.13349","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10509889","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":"Short chain fatty acids released by Fusobacterium nucleatum are neutrophil chemoattractants acting via free fatty acid receptor 2 (FFAR2)","authors":"Agnes Dahlstrand Rudin,&nbsp;Arsham Khamzeh,&nbsp;Vignesh Venkatakrishnan,&nbsp;Amina Basic,&nbsp;Karin Christenson,&nbsp;Johan Bylund","doi":"10.1111/cmi.13348","DOIUrl":"10.1111/cmi.13348","url":null,"abstract":"<p><i>Fusobacterium nucleatum</i> is a gram-negative and anaerobic oral commensal that is implicated in inflammatory conditions of the tooth-supporting structures, that is, periodontal diseases. One of the main characteristics of these conditions is an accumulation of neutrophil granulocytes in the gingival pockets where bacteria reside. Neutrophils are recruited to tissue-residing microbes by gradients of bacteria derived chemoattractants, and the cellular migration over the pocket epithelium into the gingival pocket is likely governed by chemoattractants released by the amino acid fermenting anaerobes typically colonising this site. However, the chemoattractants released by <i>F. nucleatum</i> and other oral anaerobes have long been unidentified. In the present study, we show that the major chemoattractants released during the growth of <i>F. nucleatum</i> are short chain fatty acids (SCFAs), primarily acetate and butyrate. These SCFAs, that are released at high levels as end-products of the metabolism of <i>F. nucleatum</i>, trigger chemotaxis of human neutrophils, as well as cytosolic Ca²⁺ signals, via free fatty acid receptor 2 (FFAR2). This finding establishes the SCFA-FFAR2 interaction as an important mechanism in the recruitment of neutrophils to the periodontal pocket, but could also be of importance in the pathogenesis of other medical conditions involving colonisation/infection of <i>F. nucleatum</i>.</p>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 8","pages":""},"PeriodicalIF":3.4,"publicationDate":"2021-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/cmi.13348","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38920014","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 cytostome-cytopharynx complex of intracellular and extracellular amastigotes of Trypanosoma cruzi exhibit structural and functional differences","authors":"Carolina L. Alcantara,&nbsp;Wanderley de Souza,&nbsp;Narcisa L. Cunha e Silva","doi":"10.1111/cmi.13346","DOIUrl":"10.1111/cmi.13346","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Endocytosis in <i>Trypanosoma cruzi</i> is mainly performed through a specialised membrane domain called cytostome-cytopharynx complex. Its ultrastructure and dynamics in endocytosis are well characterized in epimastigotes, being absent in trypomastigotes, that lack endocytic activity. Intracellular amastigotes also possess a cytostome-cytopharynx but participation in endocytosis of these forms is not clear. Extracellular amastigotes can be obtained from the supernatant of infected cells or in vitro amastigogenesis. These amastigotes share biochemical and morphological features with intracellular amastigotes but retain trypomastigote's ability to establish infection. We analysed and compared the ultrastructure of the cytostome-cytopharynx complex of intracellular amastigotes and extracellular amastigotes using high-resolution tridimensional electron microscopy techniques. We compared the endocytic ability of intracellular amastigotes, obtained through host cell lysis, with that of extracellular amastigotes. Intracellular amastigotes showed a cytostome-cytopharynx complex similar to epimastigotes'. However, after isolation, the complex undergoes ultrastructural modifications that progressively took to an impairment of endocytosis. Extracellular amastigotes do not possess a cytostome-cytopharynx complex nor the ability to endocytose. Those observations highlight morpho functional differences between intra and extracellular amastigotes regarding an important structure related to cell metabolism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Take Aways</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li><i>T. cruzi</i> intracellular amastigotes endocytose through the cytostome-cytopharynx complex.</li>\u0000 \u0000 <li>The cytostome-cytopharynx complex of intracellular amastigotes is ultrastructurally similar to the epimastigote.</li>\u0000 \u0000 <li>Intracellular amastigotes, once outside the host cell, disassembles the cytostome-cytopharynx membrane domain.</li>\u0000 \u0000 <li>Extracellular amastigotes do not possess a cytostome-cytopharynx either the ability to endocytose.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 9","pages":""},"PeriodicalIF":3.4,"publicationDate":"2021-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/cmi.13346","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38829800","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":"Redistribution of FLAgellar Member 8 during the trypanosome life cycle: Consequences for cell fate prediction","authors":"Estefanía Calvo-Álvarez,&nbsp;Serge Bonnefoy,&nbsp;Audrey Salles,&nbsp;Fiona E. Benson,&nbsp;Paul G. McKean,&nbsp;Philippe Bastin,&nbsp;Brice Rotureau","doi":"10.1111/cmi.13347","DOIUrl":"10.1111/cmi.13347","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>The single flagellum of African trypanosomes is essential in multiple aspects of the parasites' development. The FLAgellar Member 8 protein (FLAM8), localised to the tip of the flagellum in cultured insect forms of <i>Trypanosoma brucei</i>, was identified as a marker of the locking event that controls flagellum length. Here, we investigated whether FLAM8 could also reflect the flagellum maturation state in other parasite cycle stages. We observed that FLAM8 distribution extended along the entire flagellar cytoskeleton in mammalian-infective forms. Then, a rapid FLAM8 concentration to the distal tip occurs during differentiation into early insect forms, illustrating the remodelling of an existing flagellum. In the tsetse cardia, FLAM8 further localises to the entire length of the new flagellum during an asymmetric division. Strikingly, in parasites dividing in the tsetse midgut and in the salivary glands, the amount and distribution of FLAM8 in the new flagellum were seen to predict the daughter cell fate. We propose and discuss how FLAM8 could be considered a meta-marker of the flagellum stage and maturation state in trypanosomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 9","pages":""},"PeriodicalIF":3.4,"publicationDate":"2021-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/cmi.13347","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38905501","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 multiple functions of actin in apicomplexan parasites","authors":"Sujaan Das,&nbsp;Johannes Felix Stortz,&nbsp;Markus Meissner,&nbsp;Javier Periz","doi":"10.1111/cmi.13345","DOIUrl":"10.1111/cmi.13345","url":null,"abstract":"<p>The cytoskeletal protein actin is highly abundant and conserved in eukaryotic cells. It occurs in two different states- the globular (G-actin) form, which can polymerise into the filamentous (F-actin) form, fulfilling various critical functions including cytokinesis, cargo trafficking and cellular motility. In higher eukaryotes, there are several actin isoforms with nearly identical amino acid sequences. Despite the high level of amino acid identity, they display regulated expression patterns and unique non-redundant roles. The number of actin isoforms together with conserved sequences may reflect the selective pressure exerted by scores of actin binding proteins (ABPs) in higher eukaryotes. In contrast, in many protozoans such as apicomplexan parasites which possess only a few ABPs, the regulatory control of actin and its multiple functions are still obscure. Here, we provide a summary of the regulation and biological functions of actin in higher eukaryotes and compare it with the current knowledge in apicomplexans. We discuss future experiments that will help us understand the multiple, critical roles of this fascinating system in apicomplexans.</p>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 11","pages":""},"PeriodicalIF":3.4,"publicationDate":"2021-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/cmi.13345","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38896865","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":"Disassembly of the apical junctional complex during the transmigration of Leptospira interrogans across polarized renal proximal tubule epithelial cells","authors":"Isabel Sebastián,&nbsp;Nobuhiko Okura,&nbsp;Bruno M. Humbel,&nbsp;Jun Xu,&nbsp;Idam Hermawan,&nbsp;Chiaki Matsuura,&nbsp;Malgorzata Hall,&nbsp;Chitoshi Takayama,&nbsp;Tetsu Yamashiro,&nbsp;Shuichi Nakamura,&nbsp;Claudia Toma","doi":"10.1111/cmi.13343","DOIUrl":"10.1111/cmi.13343","url":null,"abstract":"Bacterial pathogens have evolved multiple strategies to disassemble epithelial cell apical junctional complexes (AJCs) and infect epithelial cells. Leptospirosis is a widespread zoonotic infection, mainly caused by Leptospira interrogans, and its dissemination across host cell barriers is essential for its pathogenesis. However, the mechanism of bacterial dissemination across epithelial cell barriers remains poorly characterised. In this study, we analysed the interaction of L. interrogans with renal proximal tubule epithelial cells (RPTECs) and found that at 24 hr post‐infection, L. interrogans remain in close contact with the plasma membrane of the RPTEC by extracellularly adhering or crawling. Leptospira interrogans cleaved E‐cadherin and induced its endocytosis with release of the soluble N‐terminal fragment into the extracellular medium. Concomitantly, a gradual decrease in transepithelial electrical resistance (TEER), mislocalisation of AJC proteins (occludin, claudin‐10, ZO‐1, and cingulin) and cytoskeletal rearrangement were observed. Inhibition of clathrin‐mediated E‐cadherin endocytosis prevented the decrease in TEER. We showed that disassembly of AJCs in epithelial cells and transmigration of bacteria through the paracellular route are important for the dissemination of L. interrogans in the host.","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 9","pages":""},"PeriodicalIF":3.4,"publicationDate":"2021-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/cmi.13343","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38881149","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":"Breaching the phagosome, the case of the tuberculosis agent","authors":"Roxane Simeone,&nbsp;Fadel Sayes,&nbsp;Emeline Lawarée,&nbsp;Roland Brosch","doi":"10.1111/cmi.13344","DOIUrl":"10.1111/cmi.13344","url":null,"abstract":"<p>The interactions between microbes and their hosts are among the most complex biological phenomena known today. The interaction may reach from overall beneficial interaction, as observed for most microbiome/microbiota related interactions to interaction with virulent pathogens, against which host cells have evolved sophisticated defence strategies. Among the latter, the confinement of invading pathogens in a phagosome plays a key role, which often results in the destruction of the invader, whereas some pathogens may counteract phagosomal arrest and survive by gaining access to the cytosol of the host cell. In the current review, we will discuss recent insights into this dynamic process of host-pathogen interaction, using <i>Mycobacterium tuberculosis</i> and related pathogenic mycobacteria as main examples.</p>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2021-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/cmi.13344","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38878791","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":"New methods to decrypt emerging macropinosome functions during the host–pathogen crosstalk","authors":"Yuen-Yan Chang,&nbsp;Jost Enninga,&nbsp;Virginie Stévenin","doi":"10.1111/cmi.13342","DOIUrl":"10.1111/cmi.13342","url":null,"abstract":"<p>Large volumes of liquid and other materials from the extracellular environment are internalised by eukaryotic cells via an endocytic process called macropinocytosis. It is now recognised that this fundamental and evolutionarily conserved pathway is hijacked by numerous intracellular pathogens as an entry portal to the host cell interior. Yet, an increasing number of additional cellular functions of macropinosomes in pathologic processes have been reported beyond this role for fluid internalisation. It emerges that the identity of macropinosomes can vary hugely and change rapidly during their lifetime. A deeper understanding of this important multi-faceted compartment is based on novel methods for their investigation. These methods are either imaging-based for the tracking of macropinosome dynamics, or they provide the means to extract macropinosomes at high purity for comprehensive proteomic analyses. Here, we portray these new approaches for the investigation of macropinosomes. We document how these method developments have provided insights for a new understanding of the intracellular lifestyle of the bacterial pathogens <i>Shigella</i> and <i>Salmonella</i>. We suggest that a systematic complete characterisation of macropinosome subversion with these approaches during other infection processes and pathologies will be highly beneficial for our understanding of the underlying cellular and molecular processes.</p>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2021-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/cmi.13342","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25586317","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}