Many bacterial pathogens have developed methods to overcome the defences of the host innate immune system. One such defence is the release of antimicrobial peptides (AMPs). Histones have been found to function as AMPs, in addition to their main biological function of packaging and organising DNA into nucleosomes. In this study, the Gram-positive anaerobic coccus Finegoldia magna was found to bind histones by Western blot and immunoprecipitation analysis. F. magna, which is normally a commensal of the skin and mucous membranes, is also known to act as an opportunistic pathogen and has been isolated from various clinical infection sites. It was found to bind to histones extracted from human skin epidermis through its surface and extracellular adhesion protein FAF. Through FAF binding, F. magna was protected from histone bactericidal activity. Furthermore, the histones were found to be degraded by SufA, a subtilisin-like extracellular serine protease of F. magna. Hence, the results of the present study will give more insight into how F. magna persists both as a commensal organism at the basement membrane of the skin and as an opportunistic pathogen during infection.

Keywords:
Finegoldia magna, Gram-positive anaerobic cocci, Histones, Innate immunity, SufA
1.
Murdoch DA: Gram-positive anaerobic cocci. Clin Microbiol Rev 1998;11:81-120.
2.
Murphy EC, Frick IM: Gram-positive anaerobic cocci - commensals and opportunistic pathogens. FEMS Microbiol Rev 2013;37:520-553.
3.
Hansson C, Hoborn J, Moller A, Swanbeck G: The microbial flora in venous leg ulcers without clinical signs of infection. Repeated culture using a validated standardised microbiological technique. Acta Derm Venereol 1995;75:24-30.
4.
Stephens P, Wall IB, Wilson MJ, Hill KE, Davies CE, Hill CM, Harding KG, Thomas DW: Anaerobic cocci populating the deep tissues of chronic wounds impair cellular wound healing responses in vitro. Br J Dermatol 2003;148:456-466.
5.
Bowler PG, Davies BJ: The microbiology of infected and noninfected leg ulcers. Int J Dermatol 1999;38:573-578.
6.
Levy PY, Fenollar F, Stein A, Borrione F, Raoult D: Finegoldia magna: a forgotten pathogen in prosthetic joint infection rediscovered by molecular biology. Clin Infect Dis 2009;49:1244-1247.
7.
Aldridge KE, Ashcraft D, Cambre K, Pierson CL, Jenkins SG, Rosenblatt JE: Multicenter survey of the changing in vitro antimicrobial susceptibilities of clinical isolates of Bacteroides fragilis group, Prevotella, Fusobacterium, Porphyromonas, and Peptostreptococcus species. Antimicrob Agents Chemother 2001;45:1238-1243.
8.
Brazier J, Chmelar D, Dubreuil L, Feierl G, Hedberg M, Kalenic S, Könönen E, Lundgren B, Malamou-Ladas H, Nagy E, Sullivan A, Nord CE: European surveillance study on antimicrobial susceptibility of gram-positive anaerobic cocci. Int J Antimicrob Agents 2008;31:316-320.
9.
Brazier JS, Hall V, Morris TE, Gal M, Duerden BI: Antibiotic susceptibilities of Gram-positive anaerobic cocci: results of a sentinel study in England and Wales. J Antimicrob Chemother 2003;52:224-228.
10.
Krepel CJ, Gohr CM, Walker AP, Farmer SG, Edmiston CE: Enzymatically active Peptostreptococcus magnus: association with site of infection. J Clin Microbiol 1992;30:2330-2334.
11.
Brook I: Encapsulated anaerobic bacteria in synergistic infections. Microbiol Rev 1986;50:452-457.
12.
Karlsson C, Andersson ML, Collin M, Schmidtchen A, Björck L, Frick IM: SufA - a novel subtilisin-like serine proteinase of Finegoldia magna. Microbiology 2007;153:4208-4218.
13.
Karlsson C, Mörgelin M, Collin M, Lood R, Andersson ML, Schmidtchen A, Björck L, Frick IM: SufA - a bacterial enzyme that cleaves fibrinogen and blocks fibrin network formation. Microbiology 2009;155:238-248.
14.
Karlsson C, Eliasson M, Olin AI, Mörgelin M, Karlsson A, Malmsten M, Egesten A, Frick IM: SufA of the opportunistic pathogen Finegoldia magna modulates actions of the antibacterial chemokine MIG/CXCL9, promoting bacterial survival during epithelial inflammation. J Biol Chem 2009;284:29499- 29508.
15.
Björck L: Protein l. A novel bacterial cell wall protein with affinity for Ig L chains. J Immunol 1988;140:1194-1197.
16.
Genovese A, Borgia G, Björck L, Petraroli A, de Paulis A, Piazza M, Marone G: Immunoglobulin superantigen protein L induces IL-4 and IL-13 secretion from human Fc epsilon RI+ cells through interaction with the kappa light chains of IgE. J Immunol 2003;170:1854-1861.
17.
de Château M, Björck L: Protein PAB, a mosaic albumin-binding bacterial protein representing the first contemporary example of module shuffling. J Biol Chem 1994;269:12147-12151.
18.
de Château M, Holst E, Björck L: Protein PAB, an albumin-binding bacterial surface protein promoting growth and virulence. J Biol Chem 1996;271:26609-26615.
19.
Frick IM, Karlsson C, Mörgelin M, Olin AI, Janjusevic R, Hammarstrom C, Holst E, de Château M, Björck L: Identification of a novel protein promoting the colonization and survival of Finegoldia magna, a bacterial commensal and opportunistic pathogen. Mol Microbiol 2008;70:695-708.
20.
Frick IM, Nordin SL, Baumgarten M, Mörgelin M, Sørensen OE, Olin AI, Egesten A: Constitutive and inflammation-dependent antimicrobial peptides produced by epithelium are differentially processed and inactivated by the commensal Finegoldia magna and the pathogen Streptococcus pyogenes. J Immunol 2011;187:4300-4309.
21.
Jenuwein T, Allis CD: Translating the histone code. Science 2001;293:1074-1080.
22.
Strahl BD, Allis CD: The language of covalent histone modifications. Nature 2000;403:41-45.
23.
Kim HS, Park CB, Kim MS, Kim SC: cDNA cloning and characterization of buforin I, an antimicrobial peptide: a cleavage product of histone H2A. Biochem Biophys Res Commun 1996;229:381-387.
24.
Kawasaki H, Iwamuro S: Potential roles of histones in host defense as antimicrobial agents. Infect Disord Drug Targets 2008;8:195-205.
25.
Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, Weinrauch Y, Zychlinsky A: Neutrophil extracellular traps kill bacteria. Science 2004;303:1532-1535.
26.
Lee DY, Huang CM, Nakatsuji T, Thiboutot D, Kang SA, Monestier M, Gallo RL: Histone H4 is a major component of the antimicrobial action of human sebocytes. J Invest Dermatol 2009;129:2489-2496.
27.
Neville DM Jr: Molecular weight determination of protein-dodecyl sulfate complexes by gel electrophoresis in a discontinuous buffer system. J Biol Chem 1971;246:6328-6334.
28.
Nesbitt SA, Horton MA: A nonradioactive biochemical characterization of membrane proteins using enhanced chemiluminescence. Anal Biochem 1992;206:267-272.
29.
Saussez S, Kiss R: Galectin-7. Cell Mol Life Sci 2006;63:686-697.
30.
Luger K, Mader AW, Richmond RK, Sargent DF, Richmond TJ: Crystal structure of the nucleosome core particle at 2.8 A resolution. Nature 1997;389:251-260.
31.
Cole C, Barber JD, Barton GJ: The Jpred 3 secondary structure prediction server. Nucleic Acids Res 2008;36:W197-W201.
32.
Egesten A, Eliasson M, Johansson HM, Olin AI, Mörgelin M, Mueller A, Pease JE, Frick IM, Björck L: The CXC chemokine MIG/CXCL9 is important in innate immunity against Streptococcus pyogenes. J Infect Dis 2007;195:684-693.
33.
Bourgault AM, Rosenblatt JE, Fitzgerald RH: Peptococcus magnus: a significant human pathogen. Ann Intern Med 1980;93:244-248.
34.
Kawasaki H, Isaacson T, Iwamuro S, Conlon JM: A protein with antimicrobial activity in the skin of Schlegel's green tree frog Rhacophorus schlegelii (Rhacophoridae) identified as histone H2B. Biochem Biophys Res Commun 2003;312:1082-1086.
35.
Brekken RA, Sage EH: SPARC, a matricellular protein: at the crossroads of cell-matrix. Matrix Biol 2000;19:569-580.
36.
Wu D, Ingram A, Lahti JH, Mazza B, Grenet J, Kapoor A, Liu L, Kidd VJ, Tang D: Apoptotic release of histones from nucleosomes. J Biol Chem 2002;277:12001-12008.
37.
Inazumi T, Tajima S, Nishikawa T, Kadomatsu K, Muramatsu H, Muramatsu T: Expression of the retinoid-inducible polypeptide, midkine, in human epidermal keratinocytes. Arch Dermatol Res 1997;289:471-475.
© 2013 S. Karger AG, Basel
2013
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.