How the assembly and protection of the bacterial cell envelope depend on cysteine residues

Abstract

The cell envelope of Gram-negative bacteria is a multilayered structure essential for bacterial viability; the peptidoglycan cell wall provides shape and osmotic protection to the cell, and the outer membrane serves as a permeability barrier against noxious compounds in the external environment. Assembling the envelope properly and maintaining its integrity is a matter of life and death for bacteria. Our understanding of the mechanisms of envelope assembly and maintenance has increased tremendously over the last two decades. Here, we review the major achievements during this time, giving central stage to the amino acid cysteine, one of the least abundant amino acid residues in proteins, whose unique chemical and physical properties often critically support biological processes. First, we review how cysteines contribute to envelope homeostasis by forming stabilizing disulfides in crucial bacterial assembly factors (LptD, BamA, and FtsN) and stress sensors (RcsF and NlpE). Second, we highlight the emerging role of enzymes that use cysteine residues to catalyze reactions that are necessary for proper envelope assembly, and we also explain how these enzymes are protected from oxidative inactivation. Finally, we suggest future areas of investigation, including a discussion of how cysteine residues could contribute to envelope homeostasis by functioning as redox switches. By highlighting the redox pathways that are active in the envelope of Escherichia coli, we provide a timely overview on the assembly of a cellular compartment that is the hallmark of Gram-negative bacteria.

Bacteriocins to Thwart Bacterial Resistance in Gram Negative Bacteria

“…The first obstacle to be overcome by an antimicrobial compound to reach its final target is the bacterial cell envelope (Collet et al, 2020). The extent of this barrier varies according to the target to be reached, the chemical structure of the antimicrobial compound and the bacterial species.…”

“…The cell envelope of Gram-negative bacteria consists of a phospholipid bilayer inner membrane that wraps the cytoplasm, and an asymetric outer membrane essentially composed of phospholipids at the inner leaflet and LPS at the outer leaflet, which protects the cell from the environment. In between is the periplasm that shelters a thin peptidoglycan layer (Collet et al, 2020). This double-membrane complex system and in particular the peptidoglycan, often called the cell wall, is a main target for antibiotics and antimicrobials.…”

Redox Active Antimicrobial Peptides in Controlling Growth of Microorganisms at Body Barriers

“…In Gram-negative bacteria there is an additional oxidizing system localized in the periplasm that can regulate redox-active thiols in AMPs. The envelope of Gram-negative bacteria is composed of an inner and outer membrane separated by the periplasm, which is absent in Gram-positive bacteria [ 80 , 89 ]. The periplasmic space is rich in soluble proteins that carry out important and diverse functions in bacteria such as protein folding, envelope assembly, ROS scavenging and nutrient import [ 80 , 89 , 90 ].…”

“…This is in line with a more highly oxidizing redox potential in the periplasm compared with cytoplasm [ 90 , 91 ]. In E. coli , disulfide bond formation in periplasmic proteins is catalyzed by two oxidoreductases: DsbA and DsbB [ 80 , 89 , 90 , 91 ]. Proteins that translocate to the periplasmic space react with highly oxidizing DsbA that acts as a donor of disulfide bonds.…”

Mapping the complex transcriptional landscape of the phytopathogenic bacteriumDickeya dadantii

“…Each of them contributes to the activation of the suf promoter by oxidative stress occurring during plant penetration and colonisation ( 25): the repressor Fur is inactivated by reactive oxygen species (ROS); the activator OxyR becomes active through the oxidation of two cysteine residues and the formation of a disulfide bond; IscR becomes an activator of suf promoter after destruction of its iron-sulfur cluster by ROS (94). On the other hand, the activity of L,D-transpeptidases involves a catalytic cysteine residue that must be reduced (95), which is challenging under oxidative stress. The expression of ldtC from the suf promoter, which is strongly activated in the latter condition, is therefore biologically meaningful.…”