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11.
Staphylococcus aureus Lpl protein triggers human host cell invasion via activation of Hsp90 receptor
Paula M. Tribelli Arif Luqman Minh‐Thu Nguyen Johannes Madlung Sook‐Ha Fan Boris Macek Peter Sass Katharina Bitschar Birgit Schittek Dorothee Kretschmer Friedrich Gtz 《Cellular microbiology》2020,22(1)
Staphylococcus aureus is a facultative intracellular pathogen. Recently, it has been shown that the protein part of the lipoprotein‐like lipoproteins (Lpls), encoded by the lpl cluster comprising of 10 lpls paralogue genes, increases pathogenicity, delays the G2/M phase transition, and also triggers host cell invasion. Here, we show that a recombinant Lpl1 protein without the lipid moiety binds directly to the isoforms of the human heat shock proteins Hsp90α and Hsp90ß. Synthetic peptides covering the Lpl1 sequence caused a twofold to fivefold increase of S. aureus invasion in HaCaT cells. Antibodies against Hsp90 decrease S. aureus invasion in HaCaT cells and in primary human keratinocytes. Additionally, inhibition of ATPase function of Hsp90 or silencing Hsp90α expression by siRNA also decreased the S. aureus invasion in HaCaT cells. Although the Hsp90ß is constitutively expressed, the Hsp90α isoform is heat‐inducible and appears to play a major role in Lpl1 interaction. Pre‐incubation of HaCaT cells at 39°C increased both the Hsp90α expression and S. aureus invasion. Lpl1‐Hsp90 interaction induces F‐actin formation, thus, triggering an endocytosis‐like internalisation. Here, we uncovered a new host cell invasion principle on the basis of Lpl‐Hsp90 interaction. 相似文献
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Dorothee A. Vogt Grégory Camus Eva Herker Brian R. Webster Chia-Lin Tsou Warner C. Greene Tien-Sze Benedict Yen Melanie Ott 《PLoS pathogens》2013,9(4)
The nonstructural protein NS5A has emerged as a new drug target in antiviral therapies for Hepatitis C Virus (HCV) infection. NS5A is critically involved in viral RNA replication that takes place at newly formed membranes within the endoplasmic reticulum (membranous web) and assists viral assembly in the close vicinity of lipid droplets (LDs). To identify host proteins that interact with NS5A, we performed a yeast two-hybrid screen with the N-terminus of NS5A (amino acids 1–31), a well-studied α-helical domain important for the membrane tethering of NS5A. Our studies identified the LD-associated host protein, Tail-Interacting Protein 47 (TIP47) as a novel NS5A interaction partner. Coimmunoprecipitation experiments in Huh7 hepatoma cells confirmed the interaction of TIP47 with full-length NS5A. shRNA-mediated knockdown of TIP47 caused a more than 10-fold decrease in the propagation of full-length infectious HCV in Huh7.5 hepatoma cells. A similar reduction was observed when TIP47 was knocked down in cells harboring an autonomously replicating HCV RNA (subgenomic replicon), indicating that TIP47 is required for efficient HCV RNA replication. A single point mutation (W9A) in NS5A that disrupts the interaction with TIP47 but preserves proper subcellular localization severely decreased HCV RNA replication. In biochemical membrane flotation assays, TIP47 cofractionated with HCV NS3, NS5A, NS5B proteins, and viral RNA, and together with nonstructural viral proteins was uniquely distributed to lower-density LD-rich membrane fractions in cells actively replicating HCV RNA. Collectively, our data support a model where TIP47—via its interaction with NS5A—serves as a novel cofactor for HCV infection possibly by integrating LD membranes into the membranous web. 相似文献
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Madeleine Scharf Stefan Neef Robert Freund Cornelia Geers-Kn?rr Mirita Franz-Wachtel Almuth Brandis Dorothee Krone Heike Schneider Stephanie Groos Manoj B. Menon Kin-Chow Chang Theresia Kraft Joachim D. Meissner Kenneth R. Boheler Lars S. Maier Matthias Gaestel Renate J. Scheibe 《Molecular and cellular biology》2013,33(13):2586-2602
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Mayank Singh Clayton R. Hunt Raj K. Pandita Rakesh Kumar Chin-Rang Yang Nobuo Horikoshi Robert Bachoo Sara Serag Michael D. Story Jerry W. Shay Simon N. Powell Arun Gupta Jessie Jeffery Shruti Pandita Benjamin P. C. Chen Dorothee Deckbar Markus L?brich Qin Yang Kum Kum Khanna Howard J. Worman Tej K. Pandita 《Molecular and cellular biology》2013,33(16):3390
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Hannah Deußer Dorothee Rogoll Wolfgang Scheppach Antje Volk Ralph Melcher Prof. Dr. Elke Richling 《Biotechnology journal》2013,8(3):363-370
Polyphenols contained in food have various positive effects on human health. The absorption and metabolism of polyphenols in the intestinal tract needs to be studied to estimate these effects. The Ussing chamber technique was used to investigate the transport behavior of apple polyphenols through pig small intestinal mucosa, which served as a model for human gastrointestinal mucosa. The identities and concentrations of polyphenols and their metabolites in the half-chambers (luminal and basolateral) within an incubation period of 4 h were determined by HPLC–MS/MS and HPLC–DAD (DAD = diode-array detection). Flux values were also measured. It was found that 5-caffeoylquinic acid and caffeic acid were absorbed and translocated to the basolateral side (1.9 and 3.7%, respectively), but other compounds, including glycosides of phloretin and quercetin, were observed without translocation. A Ussing chamber utilizing pig small intestinal mucosa is a suitable model for assessing the effect of apple polyphenols on mucosal integrity and nutrition absorption across porcine mucosa. 相似文献
16.
Good‐bye to tropical alpine plant giants under warmer climates? Loss of range and genetic diversity in Lobelia rhynchopetalum
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Desalegn Chala Christian Brochmann Achilleas Psomas Dorothee Ehrich Abel Gizaw Catherine A. Masao Vegar Bakkestuen Niklaus E. Zimmermann 《Ecology and evolution》2016,6(24):8931-8941
The main aim of this paper is to address consequences of climate warming on loss of habitat and genetic diversity in the enigmatic tropical alpine giant rosette plants using the Ethiopian endemic Lobelia rhynchopetalum as a model. We modeled the habitat suitability of L. rhynchopetalum and assessed how its range is affected under two climate models and four emission scenarios. We used three statistical algorithms calibrated to represent two different complexity levels of the response. We analyzed genetic diversity using amplified fragment length polymorphisms and assessed the impact of the projected range loss. Under all model and scenario combinations and consistent across algorithms and complexity levels, this afro‐alpine flagship species faces massive range reduction. Only 3.4% of its habitat seems to remain suitable on average by 2,080, resulting in loss of 82% (CI 75%–87%) of its genetic diversity. The remaining suitable habitat is projected to be fragmented among and reduced to four mountain peaks, further deteriorating the probability of long‐term sustainability of viable populations. Because of the similar morphological and physiological traits developed through convergent evolution by tropical alpine giant rosette plants in response to diurnal freeze‐thaw cycles, they most likely respond to climate change in a similar way as our study species. We conclude that specialized high‐alpine giant rosette plants, such as L. rhynchopetalum, are likely to face very high risk of extinction following climate warming. 相似文献
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Dorothee Staiger 《当今生物学》2016,46(5):275-277
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The adaptive immune system is orchestrated by CD4+ T cells. These cells detect peptides presented on Major Histocompatibility Complex (MHC) class II molecules, which are loaded in late endosomes with products of lysosomal proteolysis. One pathway by which proteins gain access to degradation in lysosomes is macroautophagy. We recently showed that constitutive macroautophagy can be detected in cells relevant for the immune system, including dendritic cells. In these antigen presenting cells, autophagosomes frequently fused with MHC class II antigen loading compartments and targeting of Influenza matrix protein 1 (MP1) for macroautophagy enhanced MHC class II presentation to MP1-specific CD4+ T cell clones up to 20 fold. Our findings indicate that macroautophagy is a constitutive and efficient pathway of antigen delivery for MHC class II presentation. We suggest that this pathway samples intracellular proteins for immune surveillance and induction of tolerance in CD4+ T cells, and could be targeted for improved MHC class II presentation of vaccine antigens. 相似文献