Loss of YhcB results in dysregulation of coordinated peptidoglycan, LPS and phospholipid synthesis during Escherichia coli cell growth

Goodall, Emily C.A. and Isom, Georgia L. and Rooke, Jessica L. and Pullela, Karthik and Icke, Christopher and Yang, Zihao and Boelter, Gabriela and Jones, Alun and Warner, Isabel and da Costa, Rochelle and Zhang, Bing and Rae, James and Tan, Wee Boon and Winkle, Matthias and Delhaye, Antoine and Heinz, Eva and Collet, Jean Francois and Cunningham, Adam F. and Blaskovich, Mark A. and Parton, Robert G. and Cole, Jeff A. and Banzhaf, Manuel and Chng, Shu Sin and Vollmer, Waldemar and Bryant, Jack A. and Henderson, Ian R. (2021) Loss of YhcB results in dysregulation of coordinated peptidoglycan, LPS and phospholipid synthesis during Escherichia coli cell growth. PLOS Genetics, 17 (12). e1009586. ISSN 1553-7390 (https://doi.org/10.1371/journal.pgen.1009586)

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Abstract

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.

ORCID iDs

Goodall, Emily C.A., Isom, Georgia L., Rooke, Jessica L., Pullela, Karthik, Icke, Christopher, Yang, Zihao, Boelter, Gabriela, Jones, Alun, Warner, Isabel, da Costa, Rochelle, Zhang, Bing, Rae, James, Tan, Wee Boon, Winkle, Matthias, Delhaye, Antoine, Heinz, Eva ORCID logoORCID: https://orcid.org/0000-0003-4413-3756, Collet, Jean Francois, Cunningham, Adam F., Blaskovich, Mark A., Parton, Robert G., Cole, Jeff A., Banzhaf, Manuel, Chng, Shu Sin, Vollmer, Waldemar, Bryant, Jack A. and Henderson, Ian R.;
  • Item type:Article
    ID code:90655
    Dates:
    Date
    Event
    23 December 2021
    Published
    24 November 2021
    Accepted
    Subjects:Science > Microbiology
    Department:UNSPECIFIED
    Depositing user: Pure Administrator
    Date deposited:23 Sep 2024 14:02
    Last modified:23 Sep 2024 14:02
    Related URLs:
    URI:https://strathprints.strath.ac.uk/id/eprint/90655
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