15 results on '"Schlatterer, Katja"'
Search Results
2. Acetate sensing by GPR43 alarms neutrophils and protects from severe sepsis
- Author
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Schlatterer, Katja, Beck, Christian, Schoppmeier, Ulrich, Peschel, Andreas, and Kretschmer, Dorothee
- Published
- 2021
- Full Text
- View/download PDF
3. Methicillin-resistant Staphylococcus aureus alters cell wall glycosylation to evade immunity
- Author
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Gerlach, David, Guo, Yinglan, De Castro, Cristina, Kim, Sun-Hwa, Schlatterer, Katja, Xu, Fei-Fei, and Pereira, Claney
- Subjects
Staphylococcus aureus -- Health aspects ,Cell walls -- Health aspects ,Glycosylation -- Health aspects ,Vaccines ,Antigens ,Staphylococcal infections ,Phosphates ,Hydroxides ,Antibodies ,Organic acids ,Immunoglobulins ,Medical schools ,Immunoglobulin G ,Enzymes ,Animal genetic engineering ,Staphylococcus aureus infections ,Microbial drug resistance ,Immune response ,Polymers ,Antigenic determinants ,Infection ,Polymer industry ,Livestock ,Environmental issues ,Science and technology ,Zoology and wildlife conservation - Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) is a frequent cause of difficult-to-treat, often fatal infections in humans.sup.1,2. Most humans have antibodies against S. aureus, but these are highly variable and often not protective in immunocompromised patients.sup.3. Previous vaccine development programs have not been successful.sup.4. A large percentage of human antibodies against S. aureus target wall teichoic acid (WTA), a ribitol-phosphate (RboP) surface polymer modified with N-acetylglucosamine (GlcNAc).sup.5,6. It is currently unknown whether the immune evasion capacities of MRSA are due to variation of dominant surface epitopes such as those associated with WTA. Here we show that a considerable proportion of the prominent healthcare-associated and livestock-associated MRSA clones CC5 and CC398, respectively, contain prophages that encode an alternative WTA glycosyltransferase. This enzyme, TarP, transfers GlcNAc to a different hydroxyl group of the WTA RboP than the standard enzyme TarS.sup.7, with important consequences for immune recognition. TarP-glycosylated WTA elicits 7.5-40-fold lower levels of immunoglobulin G in mice than TarS-modified WTA. Consistent with this, human sera contained only low levels of antibodies against TarP-modified WTA. Notably, mice immunized with TarS-modified WTA were not protected against infection with tarP-expressing MRSA, indicating that TarP is crucial for the capacity of S. aureus to evade host defences. High-resolution structural analyses of TarP bound to WTA components and uridine diphosphate GlcNAc (UDP-GlcNAc) explain the mechanism of altered RboP glycosylation and form a template for targeted inhibition of TarP. Our study reveals an immune evasion strategy of S. aureus based on averting the immunogenicity of its dominant glycoantigen WTA. These results will help with the identification of invariant S. aureus vaccine antigens and may enable the development of TarP inhibitors as a new strategy for rendering MRSA susceptible to human host defences.Strains of methicillin-resistant Staphylococcus aureus use a prophage-encoded glycosyltransferase to alter the glycosylation of their wall teichoic acid and thereby evade antibody-mediated immune responses., Author(s): David Gerlach [sup.1] [sup.2] , Yinglan Guo [sup.3] , Cristina De Castro [sup.4] , Sun-Hwa Kim [sup.5] , Katja Schlatterer [sup.1] [sup.2] , Fei-Fei Xu [sup.6] , Claney Pereira [...]
- Published
- 2018
- Full Text
- View/download PDF
4. Short-Chain Fatty Acid and FFAR2 Activation – A New Option for Treating Infections?
- Author
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Schlatterer, Katja, primary, Peschel, Andreas, additional, and Kretschmer, Dorothee, additional
- Published
- 2021
- Full Text
- View/download PDF
5. Staphylococcus aureus Depends on Eap Proteins for Preventing Degradation of Its Phenol-Soluble Modulin Toxins by Neutrophil Serine Proteases
- Author
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Kretschmer, Dorothee, Breitmeyer, Ricarda, Gekeler, Cordula, Lebtig, Marco, Schlatterer, Katja, Nega, Mulugeta, Stahl, Mark, Stapels, D.A.C., Rooijakkers, S.H.M, Peschel, Andreas, and Infectiebiologie
- Subjects
Staphylococcus aureus ,neutrophil serine proteases ,phenol-soluble modulins ,neutrophil serine proteaseinhibitors ,Staphylococci ,formyl-peptide receptor 2 - Abstract
Neutrophil granulocytes act as a first line of defense against pathogenic staphylococci. However, Staphylococcus aureus has a remarkable capacity to survive neutrophil killing, which distinguishes it from the less-pathogenic Staphylococcus epidermidis. Both species release phenol-soluble modulin (PSM) toxins, which activate the neutrophil formyl-peptide receptor 2 (FPR2) to promote neutrophil influx and phagocytosis, and which disrupt neutrophils or their phagosomal membranes at high concentrations. We show here that the neutrophil serine proteases (NSPs) neutrophil elastase, cathepsin G and proteinase 3, which are released into the extracellular space or the phagosome upon neutrophil FPR2 stimulation, effectively degrade PSMs thereby preventing their capacity to activate and destroy neutrophils. Notably, S. aureus, but not S. epidermidis, secretes potent NSP-inhibitory proteins, Eap, EapH1, EapH2, which prevented the degradation of PSMs by NSPs. Accordingly, a S. aureus mutant lacking all three NSP inhibitory proteins was less effective in activating and destroying neutrophils and it survived less well in the presence of neutrophils than the parental strain. We show that Eap proteins promote pathology via PSM-mediated FPR2 activation since murine intraperitoneal infection with the S. aureus parental but not with the NSP inhibitors mutant strain, led to a significantly higher bacterial load in the peritoneum and kidneys of mFpr2-/- compared to wild-type mice. These data demonstrate that NSPs can very effectively detoxify some of the most potent staphylococcal toxins and that the prominent human pathogen S. aureus has developed efficient inhibitors to preserve PSM functions. Preventing PSM degradation during infection represents an important survival strategy to ensure FPR2 activation.
- Published
- 2021
6. Bacterial membrane vesicles shape Staphylococcus aureus skin colonization and induction of innate immune responses
- Author
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Staudenmaier, Lena, primary, Focken, Jule, additional, Schlatterer, Katja, additional, Kretschmer, Dorothee, additional, and Schittek, Birgit, additional
- Published
- 2021
- Full Text
- View/download PDF
7. Staphylococcus aureus Depends on Eap Proteins for Preventing Degradation of Its Phenol-Soluble Modulin Toxins by Neutrophil Serine Proteases
- Author
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Infectiebiologie, Kretschmer, Dorothee, Breitmeyer, Ricarda, Gekeler, Cordula, Lebtig, Marco, Schlatterer, Katja, Nega, Mulugeta, Stahl, Mark, Stapels, D.A.C., Rooijakkers, S.H.M, Peschel, Andreas, Infectiebiologie, Kretschmer, Dorothee, Breitmeyer, Ricarda, Gekeler, Cordula, Lebtig, Marco, Schlatterer, Katja, Nega, Mulugeta, Stahl, Mark, Stapels, D.A.C., Rooijakkers, S.H.M, and Peschel, Andreas
- Published
- 2021
8. Immune modulation by molecules of Staphylococcus aureus
- Author
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Schlatterer, Katja and Peschel, Andreas (Prof. Dr.)
- Subjects
Staphylococcus aureus , Immunsystem - Abstract
Staphylococcus aureus, a major human pathogen, is the source or various infections ranging from mild skin abscesses to severe endocarditis and sepsis. The pathogenesis of S. aureus is based on the production of a wide variety of toxins and immune modulators, which can support bacterial immune evasion but also immune activation. For example, S. aureus releases the cytolytic phenol-soluble modulins (PSMs), which impair leukocyte membrane integrity, activate the human formyl-peptide receptor 2 (FPR2) and influence the release of immune-stimulatory lipoproteins (Lpps). Lpps are membrane-anchored proteins that are abundant in the S. aureus secretome although they lack a specific release system. We observed here that S. aureus membrane vesicles (MVs) contain Lpps and represent a vehicle for Lpp release. MV formation was strongly enhanced by an external turgor pressure as well as the presence of the surfactant-like PSMs, which enhanced membrane fluidity. The immune stimulatory component of Lpps is the lipid-anchor, by which Lpps are anchored in MVs. For an effective Toll-like receptor 2 (TLR2) activation, this lipid anchor has to be liberated. We could demonstrate that increasing PSM concentrations induces MV disruption and thus the release of Lpps, PSMs and other MV-associated proteins, which induce TLR2 and FPR2 activation, respectively. However, also bacterial metabolites can interact with the human immune system. Short carboxylic acids with less than six carbon atoms are the major products of bacterial fermentation or the phosphotransacetylase-acetate kinase (Pta-AckA) pathway. This group of molecules is referred to as short chain fatty acids (SCFAs) and have been described to activate the neutrophilic free-fatty acid receptor GPR43 (FFAR2). Here we could show that GPR43 activation by the SCFA member acetate transferred neutrophils into a primed state, which is characterized by an increased immune reaction towards subsequent bacterial stimulation. GPR43-dependent priming led, after restimulation with activating ligands, to increased chemotaxis and cytokine / ROS release. Furthermore, priming via GPR43 resulted in enhanced expression of Fc- and complement receptors and in improved bacterial elimination. This acetate-dependent priming was also observed in an in vivo murine sepsis model, where a GPR43-mediated priming resulted in drastically reduced bacterial loads and disease severity. In summary, in the first part we could show that S. aureus releases TLR2-activating Lpps through PSM- and turgor-driven MV-release. And in the second part we demonstrated that acetate activates neutrophils in a GPR43-dependent manner and thereby enhances the immune reaction against S. aureus.
- Published
- 2020
9. Bacterial membrane vesicles shape Staphylococcus aureus skin colonization and induction of innate immune responses.
- Author
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Staudenmaier, Lena, Focken, Jule, Schlatterer, Katja, Kretschmer, Dorothee, and Schittek, Birgit
- Subjects
BACTERIAL cell walls ,BACTERIAL colonies ,STAPHYLOCOCCUS aureus ,MEMBRANE lipids ,IMMUNE response - Abstract
Staphylococcus aureus colonization is abundant on the skin of atopic dermatitis (AD) patients where it contributes to skin inflammation. S. aureus produces virulence factors that distinguish it from commensal skin bacteria such as S. epidermidis and S. lugdunensis. However, it has remained unclear, which of these virulence factors have the strongest impact on AD. Membrane vesicles (MVs) are released by pathogenic bacteria and might play an essential role in the long‐distance delivery of bacterial effectors such as virulence factors. We show that MVs are also released by skin commensals in a similar quantity and membrane lipid amount as those from pathogenic S. aureus. Interestingly, MVs from skin commensals can protect against S. aureus skin colonization by conditioning human skin for enhanced defence. In contrast, MVs released by S. aureus are able to induce CXCL8 and TNF‐α in primary human keratinocytes, recruit neutrophils and induce neutrophil extracellular traps, which enhance S. aureus skin colonization. CXCL8 induction is TLR2‐ and NFkB‐dependent and the induction level correlates with the membrane lipid and protein A content of the MVs. Interestingly, MVs of S. aureus strains from the lesional skin of AD patients show an enhanced membrane lipid and protein A content compared to the strains from the non‐lesional sites and have an enhanced proinflammatory potential. Our data underline the complex interplay in host‐ and bacterial derived factors in S. aureus skin colonization and the important role of bacterial derived MVs and their membrane lipid and protein A content in skin inflammatory disorders. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
10. Formyl-Peptide Receptor Activation Enhances Phagocytosis of Community-Acquired Methicillin-Resistant Staphylococcus aureus
- Author
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Weiß, Elisabeth, primary, Schlatterer, Katja, additional, Beck, Christian, additional, Peschel, Andreas, additional, and Kretschmer, Dorothee, additional
- Published
- 2019
- Full Text
- View/download PDF
11. The Mechanism behind Bacterial Lipoprotein Release: Phenol-Soluble Modulins Mediate Toll-Like Receptor 2 Activation via Extracellular Vesicle Release from Staphylococcus aureus
- Author
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Schlatterer, Katja, primary, Beck, Christian, additional, Hanzelmann, Dennis, additional, Lebtig, Marco, additional, Fehrenbacher, Birgit, additional, Schaller, Martin, additional, Ebner, Patrick, additional, Nega, Mulugeta, additional, Otto, Michael, additional, Kretschmer, Dorothee, additional, and Peschel, Andreas, additional
- Published
- 2018
- Full Text
- View/download PDF
12. Formyl-Peptide Receptor Activation Enhances Phagocytosis of Community-Acquired Methicillin-Resistant Staphylococcus aureus.
- Author
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Weiß, Elisabeth, Schlatterer, Katja, Beck, Christian, Peschel, Andreas, and Kretschmer, Dorothee
- Subjects
- *
METHICILLIN-resistant staphylococcus aureus , *PHAGOCYTOSIS , *COMPLEMENT receptors , *PATTERN perception receptors , *STAPHYLOCOCCUS aureus - Abstract
Background Formyl-peptide receptors (FPRs) are important pattern recognition receptors that sense specific bacterial peptides. Formyl-peptide receptors are highly expressed on neutrophils and monocytes, and their activation promotes the migration of phagocytes to sites of infection. It is currently unknown whether FPRs may also influence subsequent processes such as bacterial phagocytosis and killing. Staphylococcus aureus , especially highly pathogenic community-acquired methicillin-resistant S aureus strains, release high amounts of FPR2 ligands, the phenol-soluble modulins. Methods We demonstrate that FPR activation leads to upregulation of complement receptors 1 and 3 as well as FCγ receptor I on neutrophils and, consequently, increased opsonic phagocytosis of S aureus and other pathogens. Results Increased phagocytosis promotes killing of S aureus and interleukin-8 release by neutrophils. Conclusions We show here for the first time that FPRs govern opsonic phagocytosis. Manipulation of FPR2 activation could open new therapeutic opportunities against bacterial pathogens. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
13. Methicillin-resistant Staphylococcus aureusalters cell wall glycosylation to evade immunity
- Author
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Gerlach, David, Guo, Yinglan, De Castro, Cristina, Kim, Sun-Hwa, Schlatterer, Katja, Xu, Fei-Fei, Pereira, Claney, Seeberger, Peter H., Ali, Sara, Codée, Jeroen, Sirisarn, Wanchat, Schulte, Berit, Wolz, Christiane, Larsen, Jesper, Molinaro, Antonio, Lee, Bok Luel, Xia, Guoqing, Stehle, Thilo, and Peschel, Andreas
- Abstract
Methicillin-resistant Staphylococcus aureus(MRSA) is a frequent cause of difficult-to-treat, often fatal infections in humans1,2. Most humans have antibodies against S. aureus, but these are highly variable and often not protective in immunocompromised patients3. Previous vaccine development programs have not been successful4. A large percentage of human antibodies against S. aureustarget wall teichoic acid (WTA), a ribitol-phosphate (RboP) surface polymer modified with N-acetylglucosamine (GlcNAc)5,6. It is currently unknown whether the immune evasion capacities of MRSA are due to variation of dominant surface epitopes such as those associated with WTA. Here we show that a considerable proportion of the prominent healthcare-associated and livestock-associated MRSA clones CC5 and CC398, respectively, contain prophages that encode an alternative WTA glycosyltransferase. This enzyme, TarP, transfers GlcNAc to a different hydroxyl group of the WTA RboP than the standard enzyme TarS7, with important consequences for immune recognition. TarP-glycosylated WTA elicits 7.5–40-fold lower levels of immunoglobulin G in mice than TarS-modified WTA. Consistent with this, human sera contained only low levels of antibodies against TarP-modified WTA. Notably, mice immunized with TarS-modified WTA were not protected against infection with tarP-expressing MRSA, indicating that TarP is crucial for the capacity of S. aureusto evade host defences. High-resolution structural analyses of TarP bound to WTA components and uridine diphosphate GlcNAc (UDP-GlcNAc) explain the mechanism of altered RboP glycosylation and form a template for targeted inhibition of TarP. Our study reveals an immune evasion strategy of S. aureusbased on averting the immunogenicity of its dominant glycoantigen WTA. These results will help with the identification of invariant S. aureusvaccine antigens and may enable the development of TarP inhibitors as a new strategy for rendering MRSA susceptible to human host defences.
- Published
- 2018
- Full Text
- View/download PDF
14. Methicillin-resistant Staphylococcus aureus alters cell wall glycosylation to evade immunity
- Author
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Yinglan Guo, Berit Schulte, Bok Luel Lee, Jeroen D. C. Codée, Christiane Wolz, Cristina De Castro, David Gerlach, Peter H. Seeberger, Sara Ali, Jesper Larsen, Antonio Molinaro, Thilo Stehle, Fei-Fei Xu, Guoqing Xia, Wanchat Sirisarn, Andreas Peschel, Claney L. Pereira, Sun-Hwa Kim, Katja Schlatterer, Gerlach, David, Guo, Yinglan, De Castro, Cristina, Kim, Sun-Hwa, Schlatterer, Katja, Xu, Fei-Fei, Pereira, Claney, Seeberger, Peter H., Ali, Sara, Codée, Jeroen, Sirisarn, Wanchat, Schulte, Berit, Wolz, Christiane, Larsen, Jesper, Molinaro, Antonio, Lee, Bok Luel, Xia, Guoqing, Stehle, Thilo, and Peschel, Andreas
- Subjects
0301 basic medicine ,Multidisciplinary ,Lydia Becker Institute ,Immunogenicity ,Biology ,medicine.disease_cause ,Methicillin-resistant Staphylococcus aureus ,Immunoglobulin G ,Epitope ,Multidisciplinary, structure, teichoic acid, X-ray, immunology ,Microbiology ,03 medical and health sciences ,030104 developmental biology ,Immune system ,Staphylococcus aureus ,Immunity ,ResearchInstitutes_Networks_Beacons/lydia_becker_institute_of_immunology_and_inflammation ,medicine ,biology.protein ,Antibody - Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) is a frequent cause of difficult-to-treat, often fatal infections in humans1,2. Most humans have antibodies against S. aureus, but these are highly variable and often not protective in immunocompromised patients3. Previous vaccine development programs have not been successful4. A large percentage of human antibodies against S. aureus target wall teichoic acid (WTA), a ribitol-phosphate (RboP) surface polymer modified with N-acetylglucosamine (GlcNAc)5,6. It is currently unknown whether the immune evasion capacities of MRSA are due to variation of dominant surface epitopes such as those associated with WTA. Here we show that a considerable proportion of the prominent healthcare-associated and livestock-associated MRSA clones CC5 and CC398, respectively, contain prophages that encode an alternative WTA glycosyltransferase. This enzyme, TarP, transfers GlcNAc to a different hydroxyl group of the WTA RboP than the standard enzyme TarS7, with important consequences for immune recognition. TarP-glycosylated WTA elicits 7.5–40-fold lower levels of immunoglobulin G in mice than TarS-modified WTA. Consistent with this, human sera contained only low levels of antibodies against TarP-modified WTA. Notably, mice immunized with TarS-modified WTA were not protected against infection with tarP-expressing MRSA, indicating that TarP is crucial for the capacity of S. aureus to evade host defences. High-resolution structural analyses of TarP bound to WTA components and uridine diphosphate GlcNAc (UDP-GlcNAc) explain the mechanism of altered RboP glycosylation and form a template for targeted inhibition of TarP. Our study reveals an immune evasion strategy of S. aureus based on averting the immunogenicity of its dominant glycoantigen WTA. These results will help with the identification of invariant S. aureus vaccine antigens and may enable the development of TarP inhibitors as a new strategy for rendering MRSA susceptible to human host defences.
- Published
- 2018
15. Staphylococcus aureus Depends on Eap Proteins for Preventing Degradation of Its Phenol-Soluble Modulin Toxins by Neutrophil Serine Proteases.
- Author
-
Kretschmer D, Breitmeyer R, Gekeler C, Lebtig M, Schlatterer K, Nega M, Stahl M, Stapels D, Rooijakkers S, and Peschel A
- Subjects
- Animals, Cells, Cultured, Humans, Mice, Mice, Inbred C57BL, Neutrophils enzymology, Serine Proteases immunology, Serine Proteases metabolism, Staphylococcal Infections immunology, Staphylococcal Infections metabolism, Staphylococcus aureus immunology, Bacterial Proteins metabolism, Bacterial Toxins metabolism, Immune Evasion immunology, Neutrophils immunology, Staphylococcus aureus metabolism
- Abstract
Neutrophil granulocytes act as a first line of defense against pathogenic staphylococci. However, Staphylococcus aureus has a remarkable capacity to survive neutrophil killing, which distinguishes it from the less-pathogenic Staphylococcus epidermidis. Both species release phenol-soluble modulin (PSM) toxins, which activate the neutrophil formyl-peptide receptor 2 (FPR2) to promote neutrophil influx and phagocytosis, and which disrupt neutrophils or their phagosomal membranes at high concentrations. We show here that the neutrophil serine proteases (NSPs) neutrophil elastase, cathepsin G and proteinase 3, which are released into the extracellular space or the phagosome upon neutrophil FPR2 stimulation, effectively degrade PSMs thereby preventing their capacity to activate and destroy neutrophils. Notably, S. aureus , but not S. epidermidis , secretes potent NSP-inhibitory proteins, Eap, EapH1, EapH2, which prevented the degradation of PSMs by NSPs. Accordingly, a S. aureus mutant lacking all three NSP inhibitory proteins was less effective in activating and destroying neutrophils and it survived less well in the presence of neutrophils than the parental strain. We show that Eap proteins promote pathology via PSM-mediated FPR2 activation since murine intraperitoneal infection with the S. aureus parental but not with the NSP inhibitors mutant strain, led to a significantly higher bacterial load in the peritoneum and kidneys of mFpr2
-/- compared to wild-type mice. These data demonstrate that NSPs can very effectively detoxify some of the most potent staphylococcal toxins and that the prominent human pathogen S. aureus has developed efficient inhibitors to preserve PSM functions. Preventing PSM degradation during infection represents an important survival strategy to ensure FPR2 activation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kretschmer, Breitmeyer, Gekeler, Lebtig, Schlatterer, Nega, Stahl, Stapels, Rooijakkers and Peschel.)- Published
- 2021
- Full Text
- View/download PDF
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