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Identification and Characterization of IgdE, a Novel IgG-degrading Protease of Streptococcus suis with Unique Specificity for Porcine IgG.
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
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2016 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 291, no 15, 7915-7925 p.Article in journal (Refereed) Published
Abstract [en]

Streptococcus suis is a major endemic pathogen of pigs causing meningitis, arthritis, and other diseases. Zoonotic S. suis infections are emerging in humans causing similar pathologies as well as severe conditions such as toxic shock-like syndrome. Recently, we discovered an IdeS family protease of S. suis that exclusively cleaves porcine IgM and represents the first virulence factor described, linking S. suis to pigs as their natural host. Here we report the identification and characterization of a novel, unrelated protease of S. suis that exclusively targets porcine IgG. This enzyme, designated IgdE for immunoglobulin G-degrading enzyme of S. suis, is a cysteine protease distinct from previous characterized streptococcal immunoglobulin degrading proteases of the IdeS family and mediates efficient cleavage of the hinge region of porcine IgG with a high degree of specificity. The findings that all S. suis strains investigated possess the IgG proteolytic activity and that piglet serum samples contain specific antibodies against IgdE strongly indicate that the protease is expressed in vivo during infection and represents a novel and putative important bacterial virulence/colonization determinant, and a thus potential therapeutic target.

Place, publisher, year, edition, pages
2016. Vol. 291, no 15, 7915-7925 p.
Keyword [en]
antibody, cysteine protease, immunoglobulin G (IgG), proteolytic enzyme, Streptococcus, substrate specificity
National Category
Other Natural Sciences Other Veterinary Science Microbiology in the medical area
Identifiers
URN: urn:nbn:se:umu:diva-118732DOI: 10.1074/jbc.M115.711440ISI: 000374056700014PubMedID: 26861873OAI: oai:DiVA.org:umu-118732DiVA: diva2:915828
Available from: 2016-03-31 Created: 2016-03-31 Last updated: 2017-05-08Bibliographically approved
In thesis
1. Streptococcal immunoglobulin degrading enzymes of the IdeS and IgdE family
Open this publication in new window or tab >>Streptococcal immunoglobulin degrading enzymes of the IdeS and IgdE family
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Bacteria of the genus Streptococcus are common asymptomatic colonisers of humans and animals. As opportunistic pathogens they can however, depending on their host’s immune status and other circumstances, cause mild to very severe infections. Streptococci are highly intertwined with specific host species, but can also cause zoonosis or anthroponosis in more uncommon hosts. Prolonged and reoccurring infections require immune evasion strategies to circumvent detection and eradication by the host’s immune defence. A substantial part of the immune defence against bacterial pathogens is mediated by immunoglobulins. This thesis is based on work to identify and characterise immunoglobulin degrading enzymes secreted by different Streptococcus species as a means to sabotage and evade antibody-mediated immune responses.

Stoichiometric and kinetic analysis of the IgG degrading enzyme IdeS from the important human pathogen S. pyogenes revealed that IdeS cleaves IgG, opposed to previous publications, as a monomer following classical Michaelis-Menten kinetics.

The IdeS homologue of S. suis, IdeSsuis, did however not cleave IgG, but was highly specific fo rporcine IgM. S. suis was found to possess yet another protease, IgdE, capable of cleaving porcine IgG. Both of these proteases were shown to promote increased bacterial survival in porcine blood during certain conditions.

IgdE is the founding member of a novel cysteine protease family (C113). Novel streptococcal members of this protease family were shown to specifically degrade certain IgG subtypes of the respective Streptococcus species’ main host. The observed substrate specificity of IgdE family proteases reflects the host tropism of these Streptococcus species, thereby giving insights into host-pathogen co-evolution.

The abundance of immunoglobulin degrading enzymes among Streptococcus species indicates the importance of evasion from the antibody mediated immune responses for streptococci. These novel identified immunoglobulin degrading enzymes of the IdeS and IgdE protease families are potential valid vaccine targets and could also be of biotechnological use.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2017. 61 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1892
Keyword
Streptococcus, S. pyogenes, S. agalactiae, S. suis, S. porcinus, S. pseudoporcinus, S. equi subsp. zooepidemicus, protease, immunoglobulin, immune evasion, IdeS, IgdE
National Category
Cell and Molecular Biology Biochemistry and Molecular Biology
Research subject
Molecular Biology
Identifiers
urn:nbn:se:umu:diva-134552 (URN)9789176016985 (ISBN)
Public defence
2017-06-01, Major Groove, Byggnad 6L, Norrlands Universitetssjukhus, Umeå, 13:00 (English)
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Available from: 2017-05-11 Created: 2017-05-08 Last updated: 2017-05-15Bibliographically approved

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Spoerry, Christianvon Pawel-Rammingen, Ulrich
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