Surface proteins of Finegoldia magna interacting with the human host

Christofer Karlsson

Surface proteins of Finegoldia magna interacting with the human host

Christofer Karlsson

Infektionsmedicin

Forskningsoutput: Avhandling › Doktorsavhandling (sammanläggning)

319 Nedladdningar (Pure)

Sammanfattning

Finegoldia magna is a Gram-positive anaerobe and a member of the normal human microflora. This bacterium is also an opportunistic pathogen and isolated from ~10% of all anaerobic infections. Reoccurring taxonomical changes and the anaerobic growth have contributed to the neglect of F. magna. The present thesis describes the identification and characterization of two novel surface proteins of F. magna.

One of the identified proteins, SufA, is a protease belonging to the subtilase family. This protease cleaves and inactivates the antimicrobial peptide LL-37 and the antibacterial chemokine MIG/CXCL9. Furthermore, the protease cleaves fibrinogen and thereby inhibits fibrin network formation. To our knowledge, the first example of directed mutagenesis of F. magna is presented with the disruption of the sufA gene.

The other identified protein is FAF. This is a cell wall attached α-helical protein that forms hair-like projections on the bacterial surface. FAF is self-associating and contributes to bacterial clumping. FAF also mediates adhesion of the bacterium to basement membranes of human skin by interacting with BM-40. A further function of FAF is blocking of the activity of antimicrobial peptides. The genes encoding faf and sufA are present in a majority of investigated isolates indicating that the proteins have important functions.

In conclusion, the findings presented in this thesis may help explain how F. magna colonizes the human host and causes opportunistic infections.

Originalspråk	engelska
Kvalifikation	Doktor
Tilldelande institution	Infektionsmedicin
Handledare	Frick, Inga-Maria, handledare Björck, Lars, handledare Collin, Mattias, handledare
Tilldelningsdatum	2008 dec. 19
Förlag	Department of Clinical Sciences, Lund University
ISBN (tryckt)	978-91-86059-87-3
Status	Published - 2008

Bibliografisk information

Defence details

Date: 2008-12-19
Time: 09:15
Place: Rune Grubb-salen, Biomedicinskt Centrum, Sölvegatan 18, 22184 Lund

External reviewer(s)

Name: O'Toole, Paul W.
Title: Dr
Affiliation: Department of Microbiology & Alimentary Pharmabiotic Centre, University College Cork, Ireland

---

This thesis is based on the following papers (I-IV).

I. SufA -a novel subtilisin-like serine proteinase of Finegoldia magna
Karlsson, C., Andersson, M-L., Collin, M., Schmidtchen, A., Björck, L.,
Frick, I-M.
Microbiology, 2007, 153: 4208-18

II. SufA – a bacterial enzyme that cleaves fibrinogen and blocks fibrin network formation
Karlsson, C., Mörgelin, M., Collin, M., Lood, R., Andersson, M-L.,
Schmidtchen, A., Björck, L,. Frick, I-M.
Microbiology Accepted

III. Identification of a novel protein promoting the colonization and survival of Finegoldia magna, a bacterial commensal and opportunistic pathogen
Frick, I-M., Karlsson, C., Mörgelin, M., Olin, A., Janjusevic, R.,
Hammarström, C., Holst, E., de Château, M., Björck, L.
Mol Microbiol, 2008, 70: 695 – 708

IV. SufA, a serine-protease of Finegoldia magna, enhances bacterial survival by modulating activities of the antibacterial chemokine MIG/CXCL9.
Karlsson, C.*, Eliasson, E.*, Olin, A, Mörgelin, M., Karlsson, A., Egesten,
A., Frick, I-M.
Manuscript

*indicates these authors as equally contributing

Ämnesklassifikation (UKÄ)

Infektionsmedicin

Tillgång till dokument

Christofer_K_Kappa

2 Artikel i vetenskaplig tidskrift

Identification of a novel protein promoting the colonization and survival of Finegoldia magna, a bacterial commensal and opportunistic pathogen.
Frick, I-M., Karlsson, C., Mörgelin, M., Olin, A. I., Janjusevic, R., Hammarström, C., Holst, E., de Château, M. & Björck, L., 2008, I: Molecular Microbiology. 70, s. 695-708
Forskningsoutput: Tidskriftsbidrag › Artikel i vetenskaplig tidskrift › Peer review
SufA--a novel subtilisin-like serine proteinase of Finegoldia magna.
Karlsson, C., Andersson, M-L., Collin, M., Schmidtchen, A., Björck, L. & Frick, I-M., 2007, I: Microbiology. 153, Pt 12, s. 4208-4218
Forskningsoutput: Tidskriftsbidrag › Artikel i vetenskaplig tidskrift › Peer review

Citera det här

@phdthesis{557f4036af5c4a53b670706720bd508c,

title = "Surface proteins of Finegoldia magna interacting with the human host",

abstract = "Finegoldia magna is a Gram-positive anaerobe and a member of the normal human microflora. This bacterium is also an opportunistic pathogen and isolated from ~10% of all anaerobic infections. Reoccurring taxonomical changes and the anaerobic growth have contributed to the neglect of F. magna. The present thesis describes the identification and characterization of two novel surface proteins of F. magna. One of the identified proteins, SufA, is a protease belonging to the subtilase family. This protease cleaves and inactivates the antimicrobial peptide LL-37 and the antibacterial chemokine MIG/CXCL9. Furthermore, the protease cleaves fibrinogen and thereby inhibits fibrin network formation. To our knowledge, the first example of directed mutagenesis of F. magna is presented with the disruption of the sufA gene. The other identified protein is FAF. This is a cell wall attached α-helical protein that forms hair-like projections on the bacterial surface. FAF is self-associating and contributes to bacterial clumping. FAF also mediates adhesion of the bacterium to basement membranes of human skin by interacting with BM-40. A further function of FAF is blocking of the activity of antimicrobial peptides. The genes encoding faf and sufA are present in a majority of investigated isolates indicating that the proteins have important functions. In conclusion, the findings presented in this thesis may help explain how F. magna colonizes the human host and causes opportunistic infections.",

keywords = "Finegoldia magna, Gram-positive anaerobic cocci, surface proteins, protease, LL-37, MIG/CXCL9, Fibrinogen, adhesion, gene disruption, bacterial aggregation, basement membranes",

author = "Christofer Karlsson",

note = "Defence details Date: 2008-12-19 Time: 09:15 Place: Rune Grubb-salen, Biomedicinskt Centrum, S{\"o}lvegatan 18, 22184 Lund External reviewer(s) Name: O'Toole, Paul W. Title: Dr Affiliation: Department of Microbiology & Alimentary Pharmabiotic Centre, University College Cork, Ireland --- This thesis is based on the following papers (I-IV). I. SufA -a novel subtilisin-like serine proteinase of Finegoldia magna Karlsson, C., Andersson, M-L., Collin, M., Schmidtchen, A., Bj{\"o}rck, L., Frick, I-M. Microbiology, 2007, 153: 4208-18 II. SufA – a bacterial enzyme that cleaves fibrinogen and blocks fibrin network formation Karlsson, C., M{\"o}rgelin, M., Collin, M., Lood, R., Andersson, M-L., Schmidtchen, A., Bj{\"o}rck, L,. Frick, I-M. Microbiology Accepted III. Identification of a novel protein promoting the colonization and survival of Finegoldia magna, a bacterial commensal and opportunistic pathogen Frick, I-M., Karlsson, C., M{\"o}rgelin, M., Olin, A., Janjusevic, R., Hammarstr{\"o}m, C., Holst, E., de Ch{\^a}teau, M., Bj{\"o}rck, L. Mol Microbiol, 2008, 70: 695 – 708 IV. SufA, a serine-protease of Finegoldia magna, enhances bacterial survival by modulating activities of the antibacterial chemokine MIG/CXCL9. Karlsson, C.*, Eliasson, E.*, Olin, A, M{\"o}rgelin, M., Karlsson, A., Egesten, A., Frick, I-M. Manuscript *indicates these authors as equally contributing",

year = "2008",

language = "English",

isbn = "978-91-86059-87-3",

series = "Lund University Faculty of Medicine Doctoral Dissertation Series ",

publisher = "Department of Clinical Sciences, Lund University",

school = "Infection Medicine (BMC)",

}

TY - THES

T1 - Surface proteins of Finegoldia magna interacting with the human host

AU - Karlsson, Christofer

N1 - Defence details Date: 2008-12-19 Time: 09:15 Place: Rune Grubb-salen, Biomedicinskt Centrum, Sölvegatan 18, 22184 Lund External reviewer(s) Name: O'Toole, Paul W. Title: Dr Affiliation: Department of Microbiology & Alimentary Pharmabiotic Centre, University College Cork, Ireland --- This thesis is based on the following papers (I-IV). I. SufA -a novel subtilisin-like serine proteinase of Finegoldia magna Karlsson, C., Andersson, M-L., Collin, M., Schmidtchen, A., Björck, L., Frick, I-M. Microbiology, 2007, 153: 4208-18 II. SufA – a bacterial enzyme that cleaves fibrinogen and blocks fibrin network formation Karlsson, C., Mörgelin, M., Collin, M., Lood, R., Andersson, M-L., Schmidtchen, A., Björck, L,. Frick, I-M. Microbiology Accepted III. Identification of a novel protein promoting the colonization and survival of Finegoldia magna, a bacterial commensal and opportunistic pathogen Frick, I-M., Karlsson, C., Mörgelin, M., Olin, A., Janjusevic, R., Hammarström, C., Holst, E., de Château, M., Björck, L. Mol Microbiol, 2008, 70: 695 – 708 IV. SufA, a serine-protease of Finegoldia magna, enhances bacterial survival by modulating activities of the antibacterial chemokine MIG/CXCL9. Karlsson, C.*, Eliasson, E.*, Olin, A, Mörgelin, M., Karlsson, A., Egesten, A., Frick, I-M. Manuscript *indicates these authors as equally contributing

PY - 2008

Y1 - 2008

N2 - Finegoldia magna is a Gram-positive anaerobe and a member of the normal human microflora. This bacterium is also an opportunistic pathogen and isolated from ~10% of all anaerobic infections. Reoccurring taxonomical changes and the anaerobic growth have contributed to the neglect of F. magna. The present thesis describes the identification and characterization of two novel surface proteins of F. magna. One of the identified proteins, SufA, is a protease belonging to the subtilase family. This protease cleaves and inactivates the antimicrobial peptide LL-37 and the antibacterial chemokine MIG/CXCL9. Furthermore, the protease cleaves fibrinogen and thereby inhibits fibrin network formation. To our knowledge, the first example of directed mutagenesis of F. magna is presented with the disruption of the sufA gene. The other identified protein is FAF. This is a cell wall attached α-helical protein that forms hair-like projections on the bacterial surface. FAF is self-associating and contributes to bacterial clumping. FAF also mediates adhesion of the bacterium to basement membranes of human skin by interacting with BM-40. A further function of FAF is blocking of the activity of antimicrobial peptides. The genes encoding faf and sufA are present in a majority of investigated isolates indicating that the proteins have important functions. In conclusion, the findings presented in this thesis may help explain how F. magna colonizes the human host and causes opportunistic infections.

AB - Finegoldia magna is a Gram-positive anaerobe and a member of the normal human microflora. This bacterium is also an opportunistic pathogen and isolated from ~10% of all anaerobic infections. Reoccurring taxonomical changes and the anaerobic growth have contributed to the neglect of F. magna. The present thesis describes the identification and characterization of two novel surface proteins of F. magna. One of the identified proteins, SufA, is a protease belonging to the subtilase family. This protease cleaves and inactivates the antimicrobial peptide LL-37 and the antibacterial chemokine MIG/CXCL9. Furthermore, the protease cleaves fibrinogen and thereby inhibits fibrin network formation. To our knowledge, the first example of directed mutagenesis of F. magna is presented with the disruption of the sufA gene. The other identified protein is FAF. This is a cell wall attached α-helical protein that forms hair-like projections on the bacterial surface. FAF is self-associating and contributes to bacterial clumping. FAF also mediates adhesion of the bacterium to basement membranes of human skin by interacting with BM-40. A further function of FAF is blocking of the activity of antimicrobial peptides. The genes encoding faf and sufA are present in a majority of investigated isolates indicating that the proteins have important functions. In conclusion, the findings presented in this thesis may help explain how F. magna colonizes the human host and causes opportunistic infections.

KW - Finegoldia magna

KW - Gram-positive anaerobic cocci

KW - surface proteins

KW - protease

KW - LL-37

KW - MIG/CXCL9

KW - Fibrinogen

KW - adhesion

KW - gene disruption

KW - bacterial aggregation

KW - basement membranes

M3 - Doctoral Thesis (compilation)

SN - 978-91-86059-87-3

T3 - Lund University Faculty of Medicine Doctoral Dissertation Series

PB - Department of Clinical Sciences, Lund University

ER -

Surface proteins of Finegoldia magna interacting with the human host

Sammanfattning

Bibliografisk information

Ämnesklassifikation (UKÄ)

Tillgång till dokument

Fingeravtryck

Forskningsoutput

Identification of a novel protein promoting the colonization and survival of Finegoldia magna, a bacterial commensal and opportunistic pathogen.

SufA--a novel subtilisin-like serine proteinase of Finegoldia magna.

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