A synergistic role for two predicted inner membrane proteins of Escherichia coli in cell envelope integrity. Issue 2 (22nd November 2018)

• Record Type: Journal Article
• Authors: Mychack, Aaron; Amrutha, R. N.; Chung, Charlie; Cardenas Arevalo, Karla; Reddy, Manjula; Janakiraman, Anuradha
• Is Part Of: Molecular microbiology. Volume 111:Issue 2(2019)
• Page Start: 317
• Page End: 337
• Publication Date: 2018-11-22
• Subjects: Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.14157
• Languages: English
• ISSNs: 0950-382X

Abstract

Summary: The bacterial cytoplasmic membrane is a principal site of protein translocation, lipid and peptidoglycan biogenesis, signal transduction, transporters and energy generating components of the respiratory chain. Although 25–30% of bacterial proteomes consist of membrane proteins, a comprehensive understanding of their influence on fundamental cellular processes is incomplete. Here, we show that YciB and DcrB, two small cytoplasmic membrane proteins of previously unknown functions, play an essential synergistic role in maintaining cell envelope integrity of Escherichia coli . Lack of both YciB and DcrB results in pleiotropic cell defects including increased levels of lipopolysaccharide, membrane vesiculation, dynamic shrinking and extension of the cytoplasmic membrane accompanied by lysis and cell death. The stalling of an abundant outer membrane lipoprotein, Lpp, at the periplasmic face of the inner membrane leads to lethal inner membrane–peptidoglycan linkages. Additionally, the periplasmic chaperone Skp contributes to yciB dcrB mutant cell death by possibly mistargeting stalled porins into the inner membrane. Consistent with the idea of a compromised envelope in the yciB dcrB mutant, multiple envelope stress response systems are induced, with Cpx signal transduction being required for growth. Taken together, our results suggest a fundamental role for YciB and DcrB in cell envelope biogenesis. Abstract : Bacterial cytoplasmic membrane serves as the primary site of critical membrane‐related functions such as protein secretion, lipid biogenesis and energy production that are generally performed by intracellular organelles in eukaryotes. Here, we show that two small cytoplasmic membrane proteins, YciB and DcrB, play a synergistic role in maintaining the integrity of the bacterial cell envelope. Broadly, our study identifies a previously unknown essential pathway which is a potential target for development of novel antibacterial compounds.