Download Artur Schmidtchen Work Package I. Skin and wound infections

Identification of drug targets in infectious diseases
Main applicant:
Co-applicants:
Heiko Herwald
Arne Egesten, Matthias Mörgelin, and Artur Schmidtchen
Lund University
Synergy Grant in Infection Biology
from
The Swedish Foundation for Strategic Research
Identification of drug targets in infectious diseases
Work Packages
Identification of drug targets in infectious diseases
Work Packages
Work Package I
Skin and wound infections
Identification of drug targets in infectious diseases
Work Packages
Work Package I
Skin and wound infections
Work Package II
Pulmonary Infections
Identification of drug targets in infectious diseases
Work Packages
Work Package I
Skin and wound infections
Work Package III
Deep Tissue Infections
Work Package II
Pulmonary Infections
Identification of drug targets in infectious diseases
Work Packages
Work Package I
Skin and wound infections
Work Package III
Deep Tissue Infections
Work Package II
Pulmonary Infections
Work Package IV
Systemic Infections
Identification of drug targets in infectious diseases
Work Packages
Work Package I. Skin and wound infections (Artur Schmidtchen)
a. Discoveries of novel host defense systems of skin and wounds
b. Bacterial proteolysis and interactions with host defense
c. New therapies for wounds as well as invasive infections
Work Package II. Pulmonary Infections (Arne Egesten)
a. Antibacterial responses executed by epithelial cells – the importance of presentation
b. Bacterial corruption of innate host defense
c. Anti-inflammatory host responses and resolution of inflammation with a focus on osteopontin and
citrullination
Work Package III. Deep Tissue Infections (Matthias Mörgelin)
a. Extracellular matrix components as adhesive substrates for bacteria
b. Extracellular matrix components harbor antibacterial properties
c. Do extracellular matrix molecules modulate inflammatory host responses?
Work Package IV. Systemic Infections (Heiko Herwald)
a. Identification of novel diagnostic markers in severe infectious diseases
b. Treatment of invasive infections by targeting coagulation factor X
c. Treatment of infectious diseases with Fibrogammin®P
Publications (2013 – 2017)
Artur Schmidtchen
Work Package I. Skin and wound infections
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Discoveries of novel host defense systems of skin and wounds
Bacterial proteolysis and interactions with host defense
New therapies for wounds as well as invasive infections
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9.
Saleh, K., Sonesson, A., Persson, K., Riesbeck, K. and, Schmidtchen, A. (2016) J Am Acad Dermatol. 75, 1221-1228 (Impact Factor
(IF) 5.621)
van der Plas, M. J., Bhongir, R. K., Kjellström, S., Siller, H., Kasetty, G., Mörgelin, M., and Schmidtchen, A. (2016) Nat Commun 16,
11567 (IF 11.329)
Papareddy, P., Kasetty, G., Kalle, M., Bhongir, R. K., Mörgelin, M. , Schmidtchen, A., and Malmsten, M. (2016) J Antimicrob
Chemother 71, 170-180 (IF 4.919)
Hansen, F. C., Kalle-Brune, M., van der Plas, M. J., Strömdahl, A. C., Malmsten, M., Mörgelin, M., and Schmidtchen, A. (2015) J
Immunol 194, 5397-5406 (IF 4.985)
Kasetty, G., Kalle, M., Mörgelin, M., Brune, J. C., and Schmidtchen, A. (2015) Biomaterials 53, 415-425 (IF 8.387)
Papareddy, P., Kalle, M., Bhongir, R. K., Mörgelin, M., Malmsten, M., and Schmidtchen, A. (2014) J Biol Chem 289, 29790-29800
(IF 4.258)
Kalle, M., Papareddy, P., Kasetty, G., van der Plas, M. J., Mörgelin, M., Malmsten, M., and Schmidtchen, A. (2014) PLoS One 9,
e102577 (IF 3.057)
Singh, S., Papareddy, P., Mörgelin, M., Schmidtchen, A., and Malmsten, M. (2014) Biomacromolecules 15, 1337-1345 (IF 5.583)
Papareddy, P., Kalle, M., Singh, S., Mörgelin, M., Schmidtchen, A., and Malmsten, M. (2014) Biochim Biophys Acta 1838, 12251234 (IF 3.687)
Arne Egesten
Work Package II. Pulmonary Infections
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Antibacterial responses executed by epithelial cells – the importance of presentation
Bacterial corruption of innate host defense
Anti-inflammatory host responses and resolution of inflammation with a focus on osteopontin and
citrullination
1.
Bhongir, R. K., Kasetty, G., Papareddy, P., Mörgelin, M., Herwald, H., and Egesten, A. (2017) Biochem J , [Epub ahead of print] (IF 3.562)
2.
Kasetty, G., Papareddy, P., Bhongir, R. K., and Egesten, A. (2016) J Pharmacol Exp Ther 357, 66-72 (IF 3.760)
3.
Jovic, S., Linge, H. M., Shikhagaie, M. M., Olin, A. I., Lannefors, L., Erjefält, J. S., Mörgelin, M., and Egesten, A. (2016) Mucosal Immunol 9,
112-123 (IF 6.103)
4.
Gela, A., Kasetty, G., Mörgelin, M., Bergqvist, A., Erjefält, J. S., Pease, J. E., and Egesten, A. (2016) Allergy 71, 58-67 (IF 6.335)
5.
Gela, A., Bhongir, R. K., Mori, M., Keenan, P., Mörgelin, M., Erjefält, J. S., Herwald, H., Egesten, A., and Kasetty, G. (2016) PLoS One 11,
e0146192 (IF 3.057)
6.
Påhlman, L. I., Jogi, A., Gram, M., Mori, M., and Egesten, A. (2015) BMC Pulm Med 15, 19 (IF 2.329)
7.
Jovic, S., Shikhagaie, M., Mörgelin, M., Erjefält, J. S., Kjellström, S., and Egesten, A. (2015) J Cyst Fibros 14, 453-463(IF 3.853)
8.
Gela, A., Kasetty, G., Jovic, S., Ekoff, M., Nilsson, G., Mörgelin, M., Kjellström, S., Pease, J. E., Schmidtchen, A., and Egesten, A. (2015)
Allergy 70, 161-170 (IF 6.335)
9.
Jovic, S., Shikhagaie, M., Mörgelin, M., Kjellström, S., Erjefält, J., Olin, A. I., Frick, I. M., and Egesten, A. (2014) J Innate Immun 6, 846-859
(IF 4.273)
10.
Inghammar, M., Engström, G., Ljungberg, B., Löfdahl, C. G., Roth, A., and Egesten, A. (2014) BMC Infect Dis 14, 163 (IF 2.690)
Matthias Mörgelin
Work Package III. Deep Tissue Infections
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Extracellular matrix components as adhesive substrates for bacteria
Extracellular matrix components harbor antibacterial properties
Do extracellular matrix molecules modulate inflammatory host responses?
1.
Abdillahi, S. M., Tati, R., Nordin, S. L., Baumgarten, M., Hallgren, O., Bjermer, L., Erjefält, J.,
Westergren-Thorsson, Singh, B. G., Riesbeck, K., and Mörgelin, M. (2016) PLoS Pathogens (under
revision) (IF 7.003)
2.
Abdillahi, S. M., Bober, M., Nordin, S., Hallgren, O., Baumgarten, M., Erjefält, J., Westergren-Thorsson,
G., Bjermer, L., Riesbeck, K., Egesten, A., and Mörgelin, M. (2015) J Innate Immun 7, 506-517 (IF
4.273)
Heiko Herwald
Work Package IV. Systemic Infections
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Identification of novel diagnostic markers in severe infectious diseases
Treatment of invasive infections by targeting coagulation factor X
Treatment of infectious diseases with Fibrogammin®P
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Vieira, M. L., Naudin, C., Mörgelin, M., Romero, E. C., Nascimento, A. L., and Herwald, H. (2016) PLoS Negl Trop Dis 10, e0004713 (IF
3.948)
Malmström, E., Kilsgård, O., Hauri, S., Smeds, E., Herwald, H., Malmström, L., and Malmström, J. (2016) Nat Commun 7, 10261 (IF 11.329)
Westman, J., Papareddy, P., Dahlgren, M. W., Chakrakodi, B., Norrby-Teglund, A., Smeds, E., Linder, A., Mörgelin, M., Johansson-Lindbom,
B., Egesten, A., and Herwald, H. (2015) PLoS Pathog 11, e1005319 (IF 7.003)
Persson, S. T., Wilk, L., Mörgelin, M., and Herwald, H. (2015) Infect Immun 83, 4673-4681 (IF 3.603)
Naudin, C., Hurley, S. M., Malmström, E., Plug, T., Shannon, O., Meijers, J. C., Mörgelin, M., Björck, L., and Herwald, H. (2015) Thromb
Haemost 114, 717-726 (IF 5.255)
Loof, T. G., Goldmann, O., Naudin, C., Mörgelin, M., Neumann, Y., Pils, M. C., Foster, S. J., Medina, E., and Herwald, H. (2015)
Microbiology 161, 621-627 (IF 2.268)
Westman, J., Smeds, E., Johansson, L., Mörgelin, M., Olin, A. I., Malmström, E., Linder, A., and Herwald, H. (2014) J Innate Immun 6, 819830 (IF 4.273)
Malmström, E., Davidova, A., Mörgelin, M., Linder, A., Larsen, M., Qvortrup, K., Nordenfelt, P., Shannon, O., Dzupova, O., Holub, M.,
Malmström, J., and Herwald, H. (2014) Thromb Haemost 112, 1230-1243 (IF 5.255)
Artur Schmidtchen
Work Package I. Skin and wound infections
• P. aeruginosa elastase cleaves the peptide FYT21 from thrombin
• FYT21 binds PAMPs, thereby preventing TLR dimerization and
subsequent cell activation
• A novel concept of pathogen-host interactions, where bacteria
mimic an endogenous peptide-based mechanism (host defense
peptide formation) to suppress host responses
van der Plas, M. J., Bhongir, R. K., Kjellström, S., Siller, H., Kasetty, G., Mörgelin, M., and Schmidtchen, A. (2016) Nat Commun 16, 11567
Arne Egesten
Work Package II. Pulmonary Infections
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fragmented extracellular DNA (eDNA) kills Pseudomonas
aeruginosa
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pulmonary instillation of Dnase I improves the outcome and
decrease bacterial load in a model of P. aeruginosa airway
infection
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the bacteridial activity is likely mediated by chelation of divalent
cations in the outer LPS-containing envelope of Gram-negative
bacteria
Bhongir, R. K., Kasetty, G., Papareddy, P., Mörgelin, M., Herwald, H., and Egesten, A. (2017) Biochem J , [Epub ahead of print]
Matthias Mörgelin
Work Package III. Deep Tissue Infections
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collagen VI is upregulated in the airways of COPD patients
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purified collagen VI microfibrils bind to Moraxella catarrhalis
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bacteria are killed upon exposure to collagen VI
Abdillahi, S. M., Bober, M., Nordin, S., Hallgren, O., Baumgarten, M., Erjefält, J., Westergren-Thorsson, G., Bjermer, L., Riesbeck, K.,
Egesten, A., and Mörgelin, M. (2015) J Innate Immun 7, 506-517
Heiko Herwald
Work Package IV. Systemic Infections
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extracellular histones have toxic effects under sepsis conditions
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extracellular histones can induce the release of chemokines such
as CXCL9 and CXCL10
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this chemotactic activity is TLR4 dependent
Westman, J., Papareddy, P., Dahlgren, M. W., Chakrakodi, B., Norrby-Teglund, A., Smeds, E., Linder, A., Mörgelin, M., Johansson-Lindbom,
B., Egesten, A., and Herwald, H. (2015) PLoS Pathog 11, e1005319
Technology Platform
 Sandra Jovic
 Maria Baumgarten
Companies and Patents
Companies:
In2cure AB
(Artur Schmidtchen)
Colzyx AB
(Matthias Mörgelin)
InnDefense AB
(Arne Egesten and Heiko Herwald)
Patents: 3 filed patents, 1 in preparation
Future Directions
• Need for new diagnostics tools improve
clinical decision making
• Urgent need for new therapeutic strategies in
the light of resistance to conventional
antibiotics