Phosphopantetheinyl transferase ClbA contributes to the virulence of avian pathogenic Escherichia coli in meningitis infection of mice.
Avian pathogenic Escherichia coli (APEC), which has potential zoonotic risk, can cause severe systemic infections such as septicemia and meningitis in poultry. Colibactin is a hybrid non-ribosomal peptide/polyketide secondary metabolite produced by bacteria, which induces double-strand DNA breaks an...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0269102 |
| _version_ | 1811214601663021056 |
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| author | Xia Meng Yanfei Chen Peili Wang Pengpeng Xia Jinqiu Wang Mengping He Chunhong Zhu Heng Wang Guoqiang Zhu |
| author_facet | Xia Meng Yanfei Chen Peili Wang Pengpeng Xia Jinqiu Wang Mengping He Chunhong Zhu Heng Wang Guoqiang Zhu |
| author_sort | Xia Meng |
| collection | DOAJ |
| description | Avian pathogenic Escherichia coli (APEC), which has potential zoonotic risk, can cause severe systemic infections such as septicemia and meningitis in poultry. Colibactin is a hybrid non-ribosomal peptide/polyketide secondary metabolite produced by bacteria, which induces double-strand DNA breaks and chromosome instability in eukaryotic cells. ClbA is a 4'-phosphopantetheinyl transferase (PPTase) that is essential for colibactin and plays a role in siderophore synthesis. However, whether ClbA is associated with meningitis development in APEC is unclear. In this study, we abolished the clbA gene in the APEC XM strain, investigated the effect of clbA on colibactin synthesis and evaluated the pathogenic capacity of colibactin on meningitis development. Deletion of clbA reduced DNA damage to cells and hindered the normal synthesis of colibactin. Compared with the mice infected by wild-type APEC XM, the clbA deletion mutant infected mice had significant reduction in a series of characteristics associated with meningitis including clinical symptoms, bacterial loads of blood and brain, disruption of the blood brain barrier and the expression of inflammatory factors in the brain tissue. Complementation of ClbA recovered some APEC XM virulence. We conclude that ClbA is obligatory for the synthesis of colibactin and is responsible for the development of meningitis in mice infected by APEC. |
| first_indexed | 2024-04-12T06:07:20Z |
| format | Article |
| id | doaj.art-82ecf98f861a46399984c1f3a518e983 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T06:07:20Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-82ecf98f861a46399984c1f3a518e9832022-12-22T03:44:50ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01177e026910210.1371/journal.pone.0269102Phosphopantetheinyl transferase ClbA contributes to the virulence of avian pathogenic Escherichia coli in meningitis infection of mice.Xia MengYanfei ChenPeili WangPengpeng XiaJinqiu WangMengping HeChunhong ZhuHeng WangGuoqiang ZhuAvian pathogenic Escherichia coli (APEC), which has potential zoonotic risk, can cause severe systemic infections such as septicemia and meningitis in poultry. Colibactin is a hybrid non-ribosomal peptide/polyketide secondary metabolite produced by bacteria, which induces double-strand DNA breaks and chromosome instability in eukaryotic cells. ClbA is a 4'-phosphopantetheinyl transferase (PPTase) that is essential for colibactin and plays a role in siderophore synthesis. However, whether ClbA is associated with meningitis development in APEC is unclear. In this study, we abolished the clbA gene in the APEC XM strain, investigated the effect of clbA on colibactin synthesis and evaluated the pathogenic capacity of colibactin on meningitis development. Deletion of clbA reduced DNA damage to cells and hindered the normal synthesis of colibactin. Compared with the mice infected by wild-type APEC XM, the clbA deletion mutant infected mice had significant reduction in a series of characteristics associated with meningitis including clinical symptoms, bacterial loads of blood and brain, disruption of the blood brain barrier and the expression of inflammatory factors in the brain tissue. Complementation of ClbA recovered some APEC XM virulence. We conclude that ClbA is obligatory for the synthesis of colibactin and is responsible for the development of meningitis in mice infected by APEC.https://doi.org/10.1371/journal.pone.0269102 |
| spellingShingle | Xia Meng Yanfei Chen Peili Wang Pengpeng Xia Jinqiu Wang Mengping He Chunhong Zhu Heng Wang Guoqiang Zhu Phosphopantetheinyl transferase ClbA contributes to the virulence of avian pathogenic Escherichia coli in meningitis infection of mice. PLoS ONE |
| title | Phosphopantetheinyl transferase ClbA contributes to the virulence of avian pathogenic Escherichia coli in meningitis infection of mice. |
| title_full | Phosphopantetheinyl transferase ClbA contributes to the virulence of avian pathogenic Escherichia coli in meningitis infection of mice. |
| title_fullStr | Phosphopantetheinyl transferase ClbA contributes to the virulence of avian pathogenic Escherichia coli in meningitis infection of mice. |
| title_full_unstemmed | Phosphopantetheinyl transferase ClbA contributes to the virulence of avian pathogenic Escherichia coli in meningitis infection of mice. |
| title_short | Phosphopantetheinyl transferase ClbA contributes to the virulence of avian pathogenic Escherichia coli in meningitis infection of mice. |
| title_sort | phosphopantetheinyl transferase clba contributes to the virulence of avian pathogenic escherichia coli in meningitis infection of mice |
| url | https://doi.org/10.1371/journal.pone.0269102 |
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