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

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: 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. (2021) 'Loss of YhcB results in dysregulation of coordinated peptidoglycan, LPS and phospholipid synthesis during Escherichia coli cell growth'. PLoS Genetics, Vol 17, Issue 12, e1009586.

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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.

Item Type:	Article
Subjects:	QU Biochemistry > Genetics > QU 450 General Works QW Microbiology and Immunology > Bacteria > QW 138 Enterobacteriaceae
Faculty: Department:	Biological Sciences > Vector Biology Department
Digital Object Identifer (DOI):	https://doi.org/10.1371/journal.pgen.1009586
SWORD Depositor:	JISC Pubrouter
Depositing User:	Stacy Murtagh
Date Deposited:	04 Jan 2022 10:01
Last Modified:	04 Jan 2022 10:01
URI:	https://archive.lstmed.ac.uk/id/eprint/19744

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