Surface proteins of Finegoldia magna interacting with the human host

Christofer Karlsson

Surface proteins of Finegoldia magna interacting with the human host

Christofer Karlsson

Infection Medicine (BMC)

Research output: Thesis › Doctoral Thesis (compilation)

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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.

Original language	English
Qualification	Doctor
Awarding Institution	Infection Medicine (BMC)
Supervisors/Advisors	Frick, Inga-Maria, Supervisor Björck, Lars, Supervisor Collin, Mattias, Supervisor
Award date	2008 Dec 19
Publisher	Department of Clinical Sciences, Lund University
ISBN (Print)	978-91-86059-87-3
Publication status	Published - 2008

Bibliographical note

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

Subject classification (UKÄ)

Infectious Medicine

Free keywords

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

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2 Article

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, In: Molecular Microbiology. 70, p. 695-708
Research output: Contribution to journal › Article › 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, In: Microbiology. 153, Pt 12, p. 4208-4218
Research output: Contribution to journal › Article › peer-review

Cite this

@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",

type = "Doctoral Thesis (compilation)",

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

Abstract

Bibliographical note

Subject classification (UKÄ)

Free keywords

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Research output

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.

Cite this