The Experts below are selected from a list of 159 Experts worldwide ranked by ideXlab platform
Jan Potempa - One of the best experts on this subject based on the ideXlab platform.
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intracellular staphylococcus aureus employs the cysteine protease Staphopain a to induce host cell death in epithelial cells
PLOS Pathogens, 2021Co-Authors: Kathrin Stelzner, Jan Potempa, Aziza Boyny, Tobias Hertlein, Aneta Sroka, Adriana Moldovan, Kerstin Paprotka, David Kessie, Helene MehlingAbstract:Staphylococcus aureus is a major human pathogen, which can invade and survive in non-professional and professional phagocytes. Uptake by host cells is thought to contribute to pathogenicity and persistence of the bacterium. Upon internalization by epithelial cells, cytotoxic S. aureus strains can escape from the phagosome, replicate in the cytosol and induce host cell death. Here, we identified a staphylococcal cysteine protease to induce cell death after translocation of intracellular S. aureus into the host cell cytoplasm. We demonstrated that loss of Staphopain A function leads to delayed onset of host cell death and prolonged intracellular replication of S. aureus in epithelial cells. Overexpression of Staphopain A in a non-cytotoxic strain facilitated intracellular killing of the host cell even in the absence of detectable intracellular replication. Moreover, Staphopain A contributed to efficient colonization of the lung in a mouse pneumonia model. In phagocytic cells, where intracellular S. aureus is exclusively localized in the phagosome, Staphopain A did not contribute to cytotoxicity. Our study suggests that Staphopain A is utilized by S. aureus to exit the epithelial host cell and thus contributes to tissue destruction and dissemination of infection.
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intracellular staphylococcus aureus employs the cysteine protease Staphopain a to induce host cell death in epithelial cells
bioRxiv, 2020Co-Authors: Kathrin Stelzner, Jan Potempa, Tobias Hertlein, Aneta Sroka, Adriana Moldovan, Kerstin Paprotka, David Kessie, Helene Mehling, Knut OhlsenAbstract:Abstract Staphylococcus aureus is a major human pathogen, which can invade and survive in non-professional and professional phagocytes. Intracellularity is thought to contribute to pathogenicity and persistence of the bacterium. Upon internalization by epithelial cells, cytotoxic S. aureus strains can escape from the phagosome, replicate in the cytosol and induce host cell death. Here, we identified a staphylococcal cysteine protease to induce cell death by intracellular S. aureus after translocation into the host cell cytoplasm. We demonstrated that loss of Staphopain A function leads to delayed onset of host cell death and prolonged intracellular replication of S. aureus in epithelial cells. Overexpression of Staphopain A in a non-cytotoxic strain facilitated intracellular killing of the host cell even in the absence of detectable intracellular replication. Moreover, Staphopain A contributed to efficient colonization of the lung in a mouse pneumonia model. Our study suggests that Staphopain A is utilized by S. aureus to mediate escape from the host cell and thus contributes to tissue destruction and dissemination of infection. Author Summary Staphylococcus aureus is a well-known antibiotic-resistant pathogen that emerges in hospital and community settings and can cause a variety of diseases ranging from skin abscesses to lung inflammation and blood poisoning. The bacterium asymptomatically colonizes the upper respiratory tract and skin of about one third of the human population and takes advantage of opportune conditions, like immunodeficiency or breached barriers, to cause infection. Although S. aureus is not regarded as a professional intracellular bacterium, it can be internalized by human cells and subsequently exit the host cells by induction of cell death, which is considered to cause tissue destruction and spread of infection. The bacterial virulence factors and underlying molecular mechanisms involved in the intracellular lifestyle of S. aureus remain largely unknown. We identified a bacterial cysteine protease to contribute to host cell death mediated by intracellular S. aureus. Staphopain A induced killing of the host cell after translocation of the pathogen into the cell cytosol, while bacterial proliferation was not required. Further, the protease enhanced survival of the pathogen during lung infection. These findings reveal a novel, intracellular role for the bacterial protease Staphopain A.
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Identification of bacterial biofilm and the Staphylococcus aureus derived protease, Staphopain, on the skin surface of patients with atopic dermatitis
Scientific Reports, 2017Co-Authors: Andreas Sonesson, Jan Potempa, Kornelia Przybyszewska, Sigrid Eriksson, Matthias Mörgelin, Sven Kjellström, Julia Davies, Artur SchmidtchenAbstract:Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by an impaired epidermal barrier, dysregulation of innate and adaptive immunity, and a high susceptibility to bacterial colonization and infection. In the present study, bacterial biofilm was visualized by electron microscopy at the surface of AD skin. Correspondingly, Staphylococcus aureus ( S . aureus ) isolates from lesional skin of patients with AD, produced a substantial amount of biofilm in vitro . S . aureus biofilms showed less susceptibility to killing by the antimicrobial peptide LL-37 when compared with results obtained using planktonic cells. Confocal microscopy analysis showed that LL-37 binds to the S . aureus biofilms. Immuno-gold staining of S . aureus biofilm of AD skin detected the S . aureus derived protease Staphopain adjacent to the bacteria. In vitro , Staphopain B degraded LL-37 into shorter peptide fragments. Further, LL-37 significantly inhibited S . aureus biofilm formation, but no such effects were observed for the degradation products. The data presented here provide novel information on Staphopains present in S . aureus biofilms in vivo , and illustrate the complex interplay between biofilm and LL-37 in skin of AD patients, possibly leading to a disturbed host defense, which facilitates bacterial persistence.
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bacterial biofilm and the s aureus derived protease Staphopain are present on the skin surface of patients with atopic dermatitis
Experimental Dermatology, 2016Co-Authors: Andreas Sonesson, Jan Potempa, Kornelia Przybyszewska, Matthias Mörgelin, Sven Kjellström, Julia R Davies, Artur SchmidtchenAbstract:Bacterial biofilm and the S. aureus derived protease, Staphopain, are present on the skin surface of patients with atopic dermatitis
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staphylococcal cysteine protease Staphopain b sspb induces rapid engulfment of human neutrophils and monocytes by macrophages
Biological Chemistry, 2009Co-Authors: Jan Smagur, Krzysztof Guzik, Malgorzata Bzowska, Mateusz Kuzak, Miroslaw Zarebski, Tomasz Kantyka, Michal Walski, Barbara Gajkowska, Jan PotempaAbstract:Abstract Circulating neutrophils and monocytes constitute the first line of antibacterial defence, which is responsible for the phagocytosis and killing of microorganisms. Previously, we have described that the staphylococcal cysteine proteinase Staphopain B (SspB) cleaves CD11b on peripheral blood phagocytes, inducing the rapid development of features of atypical cell death in protease-treated cells. Here, we report that exposure of phagocytes to SspB critically impairs their antibacterial functions. Specifically, SspB blocks phagocytosis of Staphylococcus aureus by both neutrophils and monocytes, represses their chemotactic activity and induces extensive, nonphlogistic clearance of SspB-treated cells by macrophages. The proteinase also cleaves CD31, a major repulsion ('do not-eat-me') signal, on the surface of neutrophils. We suggest that both proteolytic degradation of repulsion signals and induction of 'eat-me' signals on the surface of leukocytes are responsible for the observed intensive phagocytosis of SspB-treated neutrophils by human monocyte-derived macrophages. Collectively, this may lead to the depletion of functional neutrophils at the site of infection, thus facilitating staphylococcal colonisation and spreading.
Artur Schmidtchen - One of the best experts on this subject based on the ideXlab platform.
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Identification of bacterial biofilm and the Staphylococcus aureus derived protease, Staphopain, on the skin surface of patients with atopic dermatitis
Scientific Reports, 2017Co-Authors: Andreas Sonesson, Jan Potempa, Kornelia Przybyszewska, Sigrid Eriksson, Matthias Mörgelin, Sven Kjellström, Julia Davies, Artur SchmidtchenAbstract:Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by an impaired epidermal barrier, dysregulation of innate and adaptive immunity, and a high susceptibility to bacterial colonization and infection. In the present study, bacterial biofilm was visualized by electron microscopy at the surface of AD skin. Correspondingly, Staphylococcus aureus ( S . aureus ) isolates from lesional skin of patients with AD, produced a substantial amount of biofilm in vitro . S . aureus biofilms showed less susceptibility to killing by the antimicrobial peptide LL-37 when compared with results obtained using planktonic cells. Confocal microscopy analysis showed that LL-37 binds to the S . aureus biofilms. Immuno-gold staining of S . aureus biofilm of AD skin detected the S . aureus derived protease Staphopain adjacent to the bacteria. In vitro , Staphopain B degraded LL-37 into shorter peptide fragments. Further, LL-37 significantly inhibited S . aureus biofilm formation, but no such effects were observed for the degradation products. The data presented here provide novel information on Staphopains present in S . aureus biofilms in vivo , and illustrate the complex interplay between biofilm and LL-37 in skin of AD patients, possibly leading to a disturbed host defense, which facilitates bacterial persistence.
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bacterial biofilm and the s aureus derived protease Staphopain are present on the skin surface of patients with atopic dermatitis
Experimental Dermatology, 2016Co-Authors: Andreas Sonesson, Jan Potempa, Kornelia Przybyszewska, Matthias Mörgelin, Sven Kjellström, Julia R Davies, Artur SchmidtchenAbstract:Bacterial biofilm and the S. aureus derived protease, Staphopain, are present on the skin surface of patients with atopic dermatitis
Andreas Sonesson - One of the best experts on this subject based on the ideXlab platform.
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Identification of bacterial biofilm and the Staphylococcus aureus derived protease, Staphopain, on the skin surface of patients with atopic dermatitis
Scientific Reports, 2017Co-Authors: Andreas Sonesson, Jan Potempa, Kornelia Przybyszewska, Sigrid Eriksson, Matthias Mörgelin, Sven Kjellström, Julia Davies, Artur SchmidtchenAbstract:Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by an impaired epidermal barrier, dysregulation of innate and adaptive immunity, and a high susceptibility to bacterial colonization and infection. In the present study, bacterial biofilm was visualized by electron microscopy at the surface of AD skin. Correspondingly, Staphylococcus aureus ( S . aureus ) isolates from lesional skin of patients with AD, produced a substantial amount of biofilm in vitro . S . aureus biofilms showed less susceptibility to killing by the antimicrobial peptide LL-37 when compared with results obtained using planktonic cells. Confocal microscopy analysis showed that LL-37 binds to the S . aureus biofilms. Immuno-gold staining of S . aureus biofilm of AD skin detected the S . aureus derived protease Staphopain adjacent to the bacteria. In vitro , Staphopain B degraded LL-37 into shorter peptide fragments. Further, LL-37 significantly inhibited S . aureus biofilm formation, but no such effects were observed for the degradation products. The data presented here provide novel information on Staphopains present in S . aureus biofilms in vivo , and illustrate the complex interplay between biofilm and LL-37 in skin of AD patients, possibly leading to a disturbed host defense, which facilitates bacterial persistence.
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bacterial biofilm and the s aureus derived protease Staphopain are present on the skin surface of patients with atopic dermatitis
Experimental Dermatology, 2016Co-Authors: Andreas Sonesson, Jan Potempa, Kornelia Przybyszewska, Matthias Mörgelin, Sven Kjellström, Julia R Davies, Artur SchmidtchenAbstract:Bacterial biofilm and the S. aureus derived protease, Staphopain, are present on the skin surface of patients with atopic dermatitis
Kornelia Przybyszewska - One of the best experts on this subject based on the ideXlab platform.
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Identification of bacterial biofilm and the Staphylococcus aureus derived protease, Staphopain, on the skin surface of patients with atopic dermatitis
Scientific Reports, 2017Co-Authors: Andreas Sonesson, Jan Potempa, Kornelia Przybyszewska, Sigrid Eriksson, Matthias Mörgelin, Sven Kjellström, Julia Davies, Artur SchmidtchenAbstract:Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by an impaired epidermal barrier, dysregulation of innate and adaptive immunity, and a high susceptibility to bacterial colonization and infection. In the present study, bacterial biofilm was visualized by electron microscopy at the surface of AD skin. Correspondingly, Staphylococcus aureus ( S . aureus ) isolates from lesional skin of patients with AD, produced a substantial amount of biofilm in vitro . S . aureus biofilms showed less susceptibility to killing by the antimicrobial peptide LL-37 when compared with results obtained using planktonic cells. Confocal microscopy analysis showed that LL-37 binds to the S . aureus biofilms. Immuno-gold staining of S . aureus biofilm of AD skin detected the S . aureus derived protease Staphopain adjacent to the bacteria. In vitro , Staphopain B degraded LL-37 into shorter peptide fragments. Further, LL-37 significantly inhibited S . aureus biofilm formation, but no such effects were observed for the degradation products. The data presented here provide novel information on Staphopains present in S . aureus biofilms in vivo , and illustrate the complex interplay between biofilm and LL-37 in skin of AD patients, possibly leading to a disturbed host defense, which facilitates bacterial persistence.
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bacterial biofilm and the s aureus derived protease Staphopain are present on the skin surface of patients with atopic dermatitis
Experimental Dermatology, 2016Co-Authors: Andreas Sonesson, Jan Potempa, Kornelia Przybyszewska, Matthias Mörgelin, Sven Kjellström, Julia R Davies, Artur SchmidtchenAbstract:Bacterial biofilm and the S. aureus derived protease, Staphopain, are present on the skin surface of patients with atopic dermatitis
Matthias Mörgelin - One of the best experts on this subject based on the ideXlab platform.
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Identification of bacterial biofilm and the Staphylococcus aureus derived protease, Staphopain, on the skin surface of patients with atopic dermatitis
Scientific Reports, 2017Co-Authors: Andreas Sonesson, Jan Potempa, Kornelia Przybyszewska, Sigrid Eriksson, Matthias Mörgelin, Sven Kjellström, Julia Davies, Artur SchmidtchenAbstract:Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by an impaired epidermal barrier, dysregulation of innate and adaptive immunity, and a high susceptibility to bacterial colonization and infection. In the present study, bacterial biofilm was visualized by electron microscopy at the surface of AD skin. Correspondingly, Staphylococcus aureus ( S . aureus ) isolates from lesional skin of patients with AD, produced a substantial amount of biofilm in vitro . S . aureus biofilms showed less susceptibility to killing by the antimicrobial peptide LL-37 when compared with results obtained using planktonic cells. Confocal microscopy analysis showed that LL-37 binds to the S . aureus biofilms. Immuno-gold staining of S . aureus biofilm of AD skin detected the S . aureus derived protease Staphopain adjacent to the bacteria. In vitro , Staphopain B degraded LL-37 into shorter peptide fragments. Further, LL-37 significantly inhibited S . aureus biofilm formation, but no such effects were observed for the degradation products. The data presented here provide novel information on Staphopains present in S . aureus biofilms in vivo , and illustrate the complex interplay between biofilm and LL-37 in skin of AD patients, possibly leading to a disturbed host defense, which facilitates bacterial persistence.
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bacterial biofilm and the s aureus derived protease Staphopain are present on the skin surface of patients with atopic dermatitis
Experimental Dermatology, 2016Co-Authors: Andreas Sonesson, Jan Potempa, Kornelia Przybyszewska, Matthias Mörgelin, Sven Kjellström, Julia R Davies, Artur SchmidtchenAbstract:Bacterial biofilm and the S. aureus derived protease, Staphopain, are present on the skin surface of patients with atopic dermatitis