Application of the C3-binding motif of streptococcal pyrogenic exotoxin B to protect mice from invasive group a streptococcal infection.
Group A streptococcus (GAS) is an important human pathogen that produces several extracellular exotoxins to facilitate invasion and infection. Streptococcal pyrogenic exotoxin B (SPE B) has been demonstrated to be an important virulence factor of GAS. Our previous studies indicate that SPE B cleaves...
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0117268&type=printable |
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| author | Chih-Feng Kuo Nina Tsao Miao-Hui Cheng Hsiu-Chen Yang Yu-Chieh Wang Ying-Pin Chen Kai-Jen Lin |
| author_facet | Chih-Feng Kuo Nina Tsao Miao-Hui Cheng Hsiu-Chen Yang Yu-Chieh Wang Ying-Pin Chen Kai-Jen Lin |
| author_sort | Chih-Feng Kuo |
| collection | DOAJ |
| description | Group A streptococcus (GAS) is an important human pathogen that produces several extracellular exotoxins to facilitate invasion and infection. Streptococcal pyrogenic exotoxin B (SPE B) has been demonstrated to be an important virulence factor of GAS. Our previous studies indicate that SPE B cleaves complement 3 (C3) and inhibits the activation of complement pathways. In this study, we constructed and expressed recombinant fragments of SPE B to examine the C3-binding site of SPE B. Using enzyme-linked immunosorbent assays and pull-down assays, we found that the C-terminal domain, containing amino-acid residues 345-398, of SPE B was the major binding site of human serum C3. We further identified a major, Ala376-Pro398, and a minor C3-binding motif, Gly346-Gly360, that both mediated the binding of C3 complement. Immunization with the C3-binding motifs protected mice against challenge with a lethal dose of non-invasive M49 strain GAS but not invasive M1 strains. To achieve higher efficiency against invasive M1 GAS infection, a combination of synthetic peptides derived from C-terminal epitope of streptolysin S (SLSpp) and from the major C3-binding motif of SPE B (PP6, Ala376-Pro398) was used to elicit specific immune response to those two important streptococcal exotoxins. Death rates and the severity of skin lesions decreased significantly in PP6/SLSpp-immunized mice that were infected with invasive M1 strains of GAS. These results indicate a combination of the C3-binding motif of SPE B and the protective epitope of SLS could be used as a subunit vaccine against invasive M1 strains group A streptococcal infection. |
| format | Article |
| id | doaj-art-bb95efa1c077499d8e9055c1dba0a86f |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-bb95efa1c077499d8e9055c1dba0a86f2025-08-20T03:01:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01101e011726810.1371/journal.pone.0117268Application of the C3-binding motif of streptococcal pyrogenic exotoxin B to protect mice from invasive group a streptococcal infection.Chih-Feng KuoNina TsaoMiao-Hui ChengHsiu-Chen YangYu-Chieh WangYing-Pin ChenKai-Jen LinGroup A streptococcus (GAS) is an important human pathogen that produces several extracellular exotoxins to facilitate invasion and infection. Streptococcal pyrogenic exotoxin B (SPE B) has been demonstrated to be an important virulence factor of GAS. Our previous studies indicate that SPE B cleaves complement 3 (C3) and inhibits the activation of complement pathways. In this study, we constructed and expressed recombinant fragments of SPE B to examine the C3-binding site of SPE B. Using enzyme-linked immunosorbent assays and pull-down assays, we found that the C-terminal domain, containing amino-acid residues 345-398, of SPE B was the major binding site of human serum C3. We further identified a major, Ala376-Pro398, and a minor C3-binding motif, Gly346-Gly360, that both mediated the binding of C3 complement. Immunization with the C3-binding motifs protected mice against challenge with a lethal dose of non-invasive M49 strain GAS but not invasive M1 strains. To achieve higher efficiency against invasive M1 GAS infection, a combination of synthetic peptides derived from C-terminal epitope of streptolysin S (SLSpp) and from the major C3-binding motif of SPE B (PP6, Ala376-Pro398) was used to elicit specific immune response to those two important streptococcal exotoxins. Death rates and the severity of skin lesions decreased significantly in PP6/SLSpp-immunized mice that were infected with invasive M1 strains of GAS. These results indicate a combination of the C3-binding motif of SPE B and the protective epitope of SLS could be used as a subunit vaccine against invasive M1 strains group A streptococcal infection.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0117268&type=printable |
| spellingShingle | Chih-Feng Kuo Nina Tsao Miao-Hui Cheng Hsiu-Chen Yang Yu-Chieh Wang Ying-Pin Chen Kai-Jen Lin Application of the C3-binding motif of streptococcal pyrogenic exotoxin B to protect mice from invasive group a streptococcal infection. PLoS ONE |
| title | Application of the C3-binding motif of streptococcal pyrogenic exotoxin B to protect mice from invasive group a streptococcal infection. |
| title_full | Application of the C3-binding motif of streptococcal pyrogenic exotoxin B to protect mice from invasive group a streptococcal infection. |
| title_fullStr | Application of the C3-binding motif of streptococcal pyrogenic exotoxin B to protect mice from invasive group a streptococcal infection. |
| title_full_unstemmed | Application of the C3-binding motif of streptococcal pyrogenic exotoxin B to protect mice from invasive group a streptococcal infection. |
| title_short | Application of the C3-binding motif of streptococcal pyrogenic exotoxin B to protect mice from invasive group a streptococcal infection. |
| title_sort | application of the c3 binding motif of streptococcal pyrogenic exotoxin b to protect mice from invasive group a streptococcal infection |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0117268&type=printable |
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