EndoSd: An IgG Glycan Hydrolyzing Enzyme in
            <i>Streptococcus Dysgalactiae</i>
            Subspecies
            <i>Dysgalactiae</i>

Shadnezhad, Azadeh; Naegeli, Andreas; Sjögren, Jonathan; Adamczyk, B; Leo, Fredrik; Maria, Andrea De; Karlsson, Niclas G.; Jensen, A. S.; Collin, Mattias

doi:10.2217/fmb.16.14

Cited by 17 publications

(17 citation statements)

References 54 publications

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“…6). This glycoform selectivity closely resembles that of the EndoS homolog EndoSd from S. dysgalactiae [33]. Ovine IgG contains bisecting GlcNAc and high mannose structures compared to human IgG; it also has terminal NGNA instead of N- acetylneuraminic acid (NANA) that is found in human IgG [40].…”

Section: Discussionmentioning

confidence: 90%

“…We have recently established that the related enzyme EndoS and its homolog EndoSd are not general endochitinases [33]. Therefore EndoSd was used as a negative control, while a verified chitinase from Streptomyces griseus was used as a positive control.…”

Section: Resultsmentioning

confidence: 99%

“…However, since glycobiology of the immune system, or glycoimmunology, is getting more attention, bacterial modification of glycoproteins beyond mere nutrient acquisition is indeed relevant to study in detail [9]. The activity of GH18 enzymes ranges from chitinase activity that hydrolyzes basically any polymer of GlcNAc, to more specific enzymes that hydrolyses the chitobiose core in certain glycoforms on any glycoprotein, and enzymes that are both glycoform and protein specific as exemplified by EndoS, EndoS2, EndoE, and EndoSd [12, 30, 33, 39]. Based on the similarities to the verified IgG glycan hydrolases EndoE and EndoS, we first analyzed if CP40 could hydrolyze glycans in IgG from different sources, and in the case of human IgG, also of different subclasses (Fig.…”

Section: Discussionmentioning

confidence: 99%

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CP40 from Corynebacterium pseudotuberculosis is an endo-β-N-acetylglucosaminidase

2016

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Background C. pseudotuberculosis is an important animal pathogen that causes substantial economical loss in sheep and goat farming. Zoonotic infections in humans are rare, but when they occur they are often severe and difficult to treat. One of the most studied proteins from this bacterium, the secreted protein CP40 is being developed as a promising vaccine candidate and has been characterized as a serine protease. In this study we have investigated if CP40 is an endoglycosidase rather than a protease.ResultsCP40 does not show any protease activity and contains an EndoS-like family 18 of glycoside hydrolase (chitinase) motif. It hydrolyzes biantennary glycans on both human and ovine IgGs. CP40 is not a general chitinase and cannot hydrolyze bisecting GlcNAc.ConclusionTaken together we present solid evidence for re-annotating CP40 as an EndoS-like endoglycosidase. Redefining the activity of this enzyme will facilitate subsequent studies that could give further insight into immune evasion mechanisms underlying corynebacterial infections in animals and humans.

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Section: Discussionmentioning

confidence: 90%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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CP40 from Corynebacterium pseudotuberculosis is an endo-β-N-acetylglucosaminidase

2016

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“…This makes GAS a very proficient evader of IgG-mediated immunity, a fact that has implications for the treatment of severe GAS infections and has to be taken into account in future research into the immune response to GAS as well as in the continuing efforts at development of an effective vaccine against the pathogen. Finally, immune evasion through modification of IgG glycosylation might not be restricted to GAS and enzymes similar to EndoS can be found in many other pathogenic species such as Enterococcus faecali s 60 , Streptococcus pneumoniae 61 as well as other non-group A streptococci 62,63 . Indeed, an EndoS homolog from Streptococcus equi 63 proved a protective antigen in a vaccination trial in mice, pointing towards its importance for the infection process.…”

Section: Discussionmentioning

confidence: 99%

Sweet revenge -Streptococcus pyogenesshowcases first example of immune evasion through specific IgG glycan hydrolysis

Naegeli

Bratanis

Karlsson

et al. 2019

Preprint

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13Streptococcus pyogenes (Group A streptococcus, GAS) is an important human pathogen 14 responsible for a wide variety of diseases from uncomplicated tonsillitis to life-threatening 15 invasive infections. GAS secretes EndoS, an endoglycosidase able to specifically cleave the 16 conserved N-glycan on human IgG antibodies. In vitro, removal of this glycan impairs IgG 17 effector functions but its relevance to GAS infection in vivo is unclear. Using targeted mass 18 spectrometry, we were able to characterize the effects of EndoS on host IgG glycosylation 19 during the course of natural infections in human patients. We found substantial IgG glycan 20 hydrolysis locally at site of infection as well as systemically in the most severe cases. Using 21 these findings we were able to set up appropriate model systems to demonstrate decreased 22 resistance to phagocytic killing of GAS lacking EndoS in vitro, as well as decreased 23 virulence in a mouse model of invasive infection. This study represents the first described 24 example of specific bacterial IgG glycan hydrolysis during infection and highlights the 25 importance of IgG glycan hydrolysis for streptococcal pathogenesis. We thereby offer new 26 insights into the mechanism of immune evasion employed by this pathogen with clear 27 implications for treatment of severe GAS infections and future efforts at vaccine 28 development. 29

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“…(127). EndoSd has also been found in S. equisimilis with IgG hydrolyzing activity (128) and IdeP was identified in the group C S. phocae subsp. phocae that affects marine animals, although its function has not been confirmed (129).…”

Section: Antiphagocytic Factorsmentioning

confidence: 97%

Pathogenicity Factors in Group C and G Streptococci

2019

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This chapter is dedicated to the memory of Professor Singh Chatwal, an inspiring 'streptococcologist' who leaves us with wonderful memories of Lancefield 2002 held in Goa, India. (animal GCS), Streptococcus zooepidemicus (animal and human GCS), Streptococcus canis (animal GGS), the Streptococcus anginosus group and Streptococcus phocae (1). GCS and GGS of human origin are now considered to constitute a single subspecies, Streptococcus dysgalactiae subsp equisimilis. Therefore, the current taxonomy characterises the species as follows; S. dysgalactiae is divided into the subspecies S. dysgalactiae subsp. equisimilis and S. dysgalactiae subsp. dysgalactiae (hereafter referred to in this chapter as S. equisimilis and S. dysgalactiae). Streptococcus equi is divided into the subspecies S. equi subsp. equi and S. equi subsp. zooepidemicus (hereafter referred to as S. equi and S. zooepidemicus). On the basis of genetic evidence, Streptococcus dysgalactiae, Streptococcus equi, Streptococcus canis are more closely related to each other than to the 'S. anginosus group', and constitute species with the 'large-colony' colony phenotype. Recent data now suggests that S. equi may simply be a subclone of S. zooepidemicus (2). S. phocae is a new species expressing the group C antigen thus far only isolated from seals (3, 4). Some of these species may also contain strains which express the Lancefield group A or group F antigens (Table 2). HUMAN DISEASE AND DIAGNOSIS GCS and GGS can cause a wide range of diseases from mild to severe, both among human and animal populations. GCS and GGS generally colonize the human respiratory, gastrointestinal and genitourinary tracts, with an estimated <4% asymptomatic pharyngeal carriage rate in adults (5-7). Human invasive infections caused by GCS and GGS have been associated with underlying conditions, such as diabetes, cardiovascular diseases and chronic skin conditions (8-10). While S. dysgalactiae is considered an animal pathogen, S. equisimilis is almost exclusively a human pathogen, with increasing prevalence and overlaps in clinical manifestations with group A Streptococcus (GAS). S. equisimilis infections include acute pharyngitis, pneumonia, endocarditis, cellulitis, peritonitis, septic arthritis, bacteraemia, and toxic shock syndrome (11-23). Like GAS, S. equisimilis has also been linked to the post streptococcal sequelae rheumatic heart disease, and in high endemic areas of rheumatic fever, carriage rates of GCS/GGS have been found to be higher than GAS (24, 25).

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EndoSd: An IgG Glycan Hydrolyzing Enzyme in Streptococcus Dysgalactiae Subspecies Dysgalactiae

Cited by 17 publications

References 54 publications

CP40 from Corynebacterium pseudotuberculosis is an endo-β-N-acetylglucosaminidase

CP40 from Corynebacterium pseudotuberculosis is an endo-β-N-acetylglucosaminidase

Sweet revenge -Streptococcus pyogenesshowcases first example of immune evasion through specific IgG glycan hydrolysis

Pathogenicity Factors in Group C and G Streptococci

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