Loss of YhcB results in dysregulation of coordinated peptidoglycan, LPS and phospholipid synthesis during Escherichia coli cell growth.
The cell envelope is essential for viability in all domains of life. It retains enzymes and substrates within a confined space while providing a protective barrier to the external environment. Destabilising the envelope of bacterial pathogens is a common strategy employed by antimicrobial treatment....
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2021-12-01
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| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1009586 |
| _version_ | 1818975011327705088 |
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| author | Emily C A Goodall Georgia L Isom Jessica L Rooke Karthik Pullela Christopher Icke Zihao Yang Gabriela Boelter Alun Jones Isabel Warner Rochelle Da Costa Bing Zhang James Rae Wee Boon Tan Matthias Winkle Antoine Delhaye Eva Heinz Jean-Francois Collet Adam F Cunningham Mark A Blaskovich Robert G Parton Jeff A Cole Manuel Banzhaf Shu-Sin Chng Waldemar Vollmer Jack A Bryant Ian R Henderson |
| author_facet | Emily C A Goodall Georgia L Isom Jessica L Rooke Karthik Pullela Christopher Icke Zihao Yang Gabriela Boelter Alun Jones Isabel Warner Rochelle Da Costa Bing Zhang James Rae Wee Boon Tan Matthias Winkle Antoine Delhaye Eva Heinz Jean-Francois Collet Adam F Cunningham Mark A Blaskovich Robert G Parton Jeff A Cole Manuel Banzhaf Shu-Sin Chng Waldemar Vollmer Jack A Bryant Ian R Henderson |
| author_sort | Emily C A Goodall |
| collection | DOAJ |
| description | The cell envelope is essential for viability in all domains of life. It retains enzymes and substrates within a confined space while providing a protective barrier to the external environment. Destabilising the envelope of bacterial pathogens is a common strategy employed by antimicrobial treatment. However, even in one of the best studied organisms, Escherichia coli, there remain gaps in our understanding of how the synthesis of the successive layers of the cell envelope are coordinated during growth and cell division. Here, we used a whole-genome phenotypic screen to identify mutants with a defective cell envelope. We report that loss of yhcB, a conserved gene of unknown function, results in loss of envelope stability, increased cell permeability and dysregulated control of cell size. Using whole genome transposon mutagenesis strategies, we report the comprehensive genetic interaction network of yhcB, revealing all genes with a synthetic negative and a synthetic positive relationship. These genes include those previously reported to have a role in cell envelope biogenesis. Surprisingly, we identified genes previously annotated as essential that became non-essential in a ΔyhcB background. Subsequent analyses suggest that YhcB functions at the junction of several envelope biosynthetic pathways coordinating the spatiotemporal growth of the cell, highlighting YhcB as an as yet unexplored antimicrobial target. |
| first_indexed | 2024-12-20T15:49:10Z |
| format | Article |
| id | doaj.art-ec2a22d24ae74fa89c1da995d1848199 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-20T15:49:10Z |
| publishDate | 2021-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-ec2a22d24ae74fa89c1da995d18481992022-12-21T19:34:46ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042021-12-011712e100958610.1371/journal.pgen.1009586Loss of YhcB results in dysregulation of coordinated peptidoglycan, LPS and phospholipid synthesis during Escherichia coli cell growth.Emily C A GoodallGeorgia L IsomJessica L RookeKarthik PullelaChristopher IckeZihao YangGabriela BoelterAlun JonesIsabel WarnerRochelle Da CostaBing ZhangJames RaeWee Boon TanMatthias WinkleAntoine DelhayeEva HeinzJean-Francois ColletAdam F CunninghamMark A BlaskovichRobert G PartonJeff A ColeManuel BanzhafShu-Sin ChngWaldemar VollmerJack A BryantIan R HendersonThe cell envelope is essential for viability in all domains of life. It retains enzymes and substrates within a confined space while providing a protective barrier to the external environment. Destabilising the envelope of bacterial pathogens is a common strategy employed by antimicrobial treatment. However, even in one of the best studied organisms, Escherichia coli, there remain gaps in our understanding of how the synthesis of the successive layers of the cell envelope are coordinated during growth and cell division. Here, we used a whole-genome phenotypic screen to identify mutants with a defective cell envelope. We report that loss of yhcB, a conserved gene of unknown function, results in loss of envelope stability, increased cell permeability and dysregulated control of cell size. Using whole genome transposon mutagenesis strategies, we report the comprehensive genetic interaction network of yhcB, revealing all genes with a synthetic negative and a synthetic positive relationship. These genes include those previously reported to have a role in cell envelope biogenesis. Surprisingly, we identified genes previously annotated as essential that became non-essential in a ΔyhcB background. Subsequent analyses suggest that YhcB functions at the junction of several envelope biosynthetic pathways coordinating the spatiotemporal growth of the cell, highlighting YhcB as an as yet unexplored antimicrobial target.https://doi.org/10.1371/journal.pgen.1009586 |
| spellingShingle | Emily C A Goodall Georgia L Isom Jessica L Rooke Karthik Pullela Christopher Icke Zihao Yang Gabriela Boelter Alun Jones Isabel Warner Rochelle Da Costa Bing Zhang James Rae Wee Boon Tan Matthias Winkle Antoine Delhaye Eva Heinz Jean-Francois Collet Adam F Cunningham Mark A Blaskovich Robert G Parton Jeff A Cole Manuel Banzhaf Shu-Sin Chng Waldemar Vollmer Jack A Bryant Ian R Henderson Loss of YhcB results in dysregulation of coordinated peptidoglycan, LPS and phospholipid synthesis during Escherichia coli cell growth. PLoS Genetics |
| title | Loss of YhcB results in dysregulation of coordinated peptidoglycan, LPS and phospholipid synthesis during Escherichia coli cell growth. |
| title_full | Loss of YhcB results in dysregulation of coordinated peptidoglycan, LPS and phospholipid synthesis during Escherichia coli cell growth. |
| title_fullStr | Loss of YhcB results in dysregulation of coordinated peptidoglycan, LPS and phospholipid synthesis during Escherichia coli cell growth. |
| title_full_unstemmed | Loss of YhcB results in dysregulation of coordinated peptidoglycan, LPS and phospholipid synthesis during Escherichia coli cell growth. |
| title_short | Loss of YhcB results in dysregulation of coordinated peptidoglycan, LPS and phospholipid synthesis during Escherichia coli cell growth. |
| title_sort | loss of yhcb results in dysregulation of coordinated peptidoglycan lps and phospholipid synthesis during escherichia coli cell growth |
| url | https://doi.org/10.1371/journal.pgen.1009586 |
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