YdfD, a Lysis Protein of the Qin Prophage, Is a Specific Inhibitor of the IspG-Catalyzed Step in the MEP Pathway of <i>Escherichia coli</i>
Bacterial cryptic prophage (defective prophage) genes are known to drastically influence host physiology, such as causing cell growth arrest or lysis, upon expression. Many phages encode lytic proteins to destroy the cell envelope. As natural antibiotics, only a few lysis target proteins were identi...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-01-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/3/1560 |
| _version_ | 1797487301828280320 |
|---|---|
| author | Zhifang Lu Biying Wang Zhiyu Qiu Ruiling Zhang Jimin Zheng Zongchao Jia |
| author_facet | Zhifang Lu Biying Wang Zhiyu Qiu Ruiling Zhang Jimin Zheng Zongchao Jia |
| author_sort | Zhifang Lu |
| collection | DOAJ |
| description | Bacterial cryptic prophage (defective prophage) genes are known to drastically influence host physiology, such as causing cell growth arrest or lysis, upon expression. Many phages encode lytic proteins to destroy the cell envelope. As natural antibiotics, only a few lysis target proteins were identified. <i>ydfD</i> is a lytic gene from the Qin cryptic prophage that encodes a 63-amino-acid protein, the ectopic expression of which in <i>Escherichia coli</i> can cause nearly complete cell lysis rapidly. The bacterial 2-<i>C</i>-methyl-D-erythritol 4-phosphate (MEP) pathway is responsible for synthesizing the isoprenoids uniquely required for sustaining bacterial growth. In this study, we provide evidence that YdfD can interact with IspG, a key enzyme involved in the MEP pathway, both in vivo and in vitro. We show that intact YdfD is required for the interaction with IspG to perform its lysis function and that the mRNA levels of <i>ydfD</i> increase significantly under certain stress conditions. Crucially, the cell lysis induced by YdfD can be abolished by the overexpression of <i>ispG</i> or the complementation of the IspG enzyme catalysis product methylerythritol 2,4-cyclodiphosphate. We propose that YdfD from the Qin cryptic prophage inhibits IspG to block the MEP pathway, leading to a compromised cell membrane and cell wall biosynthesis and eventual cell lysis. |
| first_indexed | 2024-03-09T23:46:39Z |
| format | Article |
| id | doaj.art-4b3fd5f5d43d4435a9b3ecfc78858e27 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:46:39Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-4b3fd5f5d43d4435a9b3ecfc78858e272023-11-23T16:42:32ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-01-01233156010.3390/ijms23031560YdfD, a Lysis Protein of the Qin Prophage, Is a Specific Inhibitor of the IspG-Catalyzed Step in the MEP Pathway of <i>Escherichia coli</i>Zhifang Lu0Biying Wang1Zhiyu Qiu2Ruiling Zhang3Jimin Zheng4Zongchao Jia5College of Chemistry, Beijing Normal University, Beijing 100875, ChinaCollege of Chemistry, Beijing Normal University, Beijing 100875, ChinaCollege of Chemistry, Beijing Normal University, Beijing 100875, ChinaCollege of Chemistry, Beijing Normal University, Beijing 100875, ChinaCollege of Chemistry, Beijing Normal University, Beijing 100875, ChinaDepartment of Biomedical and Molecular Sciences, Queen’s University, Kingston, ON K7L 3N6, CanadaBacterial cryptic prophage (defective prophage) genes are known to drastically influence host physiology, such as causing cell growth arrest or lysis, upon expression. Many phages encode lytic proteins to destroy the cell envelope. As natural antibiotics, only a few lysis target proteins were identified. <i>ydfD</i> is a lytic gene from the Qin cryptic prophage that encodes a 63-amino-acid protein, the ectopic expression of which in <i>Escherichia coli</i> can cause nearly complete cell lysis rapidly. The bacterial 2-<i>C</i>-methyl-D-erythritol 4-phosphate (MEP) pathway is responsible for synthesizing the isoprenoids uniquely required for sustaining bacterial growth. In this study, we provide evidence that YdfD can interact with IspG, a key enzyme involved in the MEP pathway, both in vivo and in vitro. We show that intact YdfD is required for the interaction with IspG to perform its lysis function and that the mRNA levels of <i>ydfD</i> increase significantly under certain stress conditions. Crucially, the cell lysis induced by YdfD can be abolished by the overexpression of <i>ispG</i> or the complementation of the IspG enzyme catalysis product methylerythritol 2,4-cyclodiphosphate. We propose that YdfD from the Qin cryptic prophage inhibits IspG to block the MEP pathway, leading to a compromised cell membrane and cell wall biosynthesis and eventual cell lysis.https://www.mdpi.com/1422-0067/23/3/1560lysisMEP pathwayprophageIspGYdfD |
| spellingShingle | Zhifang Lu Biying Wang Zhiyu Qiu Ruiling Zhang Jimin Zheng Zongchao Jia YdfD, a Lysis Protein of the Qin Prophage, Is a Specific Inhibitor of the IspG-Catalyzed Step in the MEP Pathway of <i>Escherichia coli</i> International Journal of Molecular Sciences lysis MEP pathway prophage IspG YdfD |
| title | YdfD, a Lysis Protein of the Qin Prophage, Is a Specific Inhibitor of the IspG-Catalyzed Step in the MEP Pathway of <i>Escherichia coli</i> |
| title_full | YdfD, a Lysis Protein of the Qin Prophage, Is a Specific Inhibitor of the IspG-Catalyzed Step in the MEP Pathway of <i>Escherichia coli</i> |
| title_fullStr | YdfD, a Lysis Protein of the Qin Prophage, Is a Specific Inhibitor of the IspG-Catalyzed Step in the MEP Pathway of <i>Escherichia coli</i> |
| title_full_unstemmed | YdfD, a Lysis Protein of the Qin Prophage, Is a Specific Inhibitor of the IspG-Catalyzed Step in the MEP Pathway of <i>Escherichia coli</i> |
| title_short | YdfD, a Lysis Protein of the Qin Prophage, Is a Specific Inhibitor of the IspG-Catalyzed Step in the MEP Pathway of <i>Escherichia coli</i> |
| title_sort | ydfd a lysis protein of the qin prophage is a specific inhibitor of the ispg catalyzed step in the mep pathway of i escherichia coli i |
| topic | lysis MEP pathway prophage IspG YdfD |
| url | https://www.mdpi.com/1422-0067/23/3/1560 |
| work_keys_str_mv | AT zhifanglu ydfdalysisproteinoftheqinprophageisaspecificinhibitoroftheispgcatalyzedstepinthemeppathwayofiescherichiacolii AT biyingwang ydfdalysisproteinoftheqinprophageisaspecificinhibitoroftheispgcatalyzedstepinthemeppathwayofiescherichiacolii AT zhiyuqiu ydfdalysisproteinoftheqinprophageisaspecificinhibitoroftheispgcatalyzedstepinthemeppathwayofiescherichiacolii AT ruilingzhang ydfdalysisproteinoftheqinprophageisaspecificinhibitoroftheispgcatalyzedstepinthemeppathwayofiescherichiacolii AT jiminzheng ydfdalysisproteinoftheqinprophageisaspecificinhibitoroftheispgcatalyzedstepinthemeppathwayofiescherichiacolii AT zongchaojia ydfdalysisproteinoftheqinprophageisaspecificinhibitoroftheispgcatalyzedstepinthemeppathwayofiescherichiacolii |