Mechanisms conferring bacterial cell wall variability and adaptivity

Abstract

The bacterial cell wall, a sophisticated and dynamic structure predominantly composed of peptidoglycan (PG), plays a pivotal role in bacterial survival and adaptation. Bacteria actively modify their cell walls by editing PG components in response to environmental challenges. Diverse variations in peptide composition, cross-linking patterns, and glycan strand structures empower bacteria to resist antibiotics, evade host immune detection, and adapt to dynamic environments. This review comprehensively summarizes the most common modifications reported to date and their associated adaptive role and further highlights how regulation of PG synthesis and turnover provides resilience to cell lysis.

Keywords: adaptation; antibiotic resistance; host-pathogen interaction; peptidoglycan.

Figure 1.. Chemical structure of peptidoglycan with enzymatic cleavage sites.

Schematic representation of the archetypal structure of muropeptides consisting of NAG-NAM disaccharides attached to a peptide chain containing 2–5 typical amino acid residues. In this model, a DD-cross-linking (product of DD-transpeptidation by PBPs) is shown (blue dashed line). The main enzymatic degradative activities involved in PG adaptation are shown with their respective cleavage sites. NAG, N-acetyl-glucosamine; NAM, N-acetyl muramic acid; L-Ala, L-Alanine; D-Glu-(γ), D-glutamic acid; mesoDap or DAP, meso-diaminopimelic acid (Gram-negatives); L-Lys, L-lysine (Gram-positives); D-Ala, D-Alanine.

Figure 2.. Structural substitutions and modifications in the peptide stem.

Possible structural substitutions (in green) and modifications/links (in red) to the α-carboxylate of D-Glu are described at the peptide moiety in peptidoglycan. NAG, N-acetyl-glucosamine; NAM, N-acetyl muramic acid; L-Ala, L-Alanine; D-Glu-(γ), D-glutamic acid; DAB, 2,4-diaminobutyric acid; DAHP, 2,6-diamino-3-hydroxypimelic acid; Hyl, hydroxylysine; Lan, lanthionine; Orn, ornithine; DAP, meso-diaminopimelic acid; L-Lys, L-lysine; D-Ala, D-Alanine; D-Ser, D-Serine; Gly, glycine; NCDAA, non-canonical D-amino acids.

Figure 3.. Bacterial adaptation to environmental stress.

Schematic diagram explaining how bacteria adapt to environmental stresses: In the presence of environmental stress, bacteria have several adaptive strategies such as programmed cell death (PCD) in certain cells of the population to provide nutrients and recyclable metabolic remnants for the survivors. They also provide genetic material and post-lysis signals capable of modifying the expression of resistance determinants. Another option is the overexpression of autolysins to produce protoplasts or unwalled cells, which are unable to proliferate due to oxidative damage brought on by the buildup of reactive oxygen species (ROS), from aerobic respiration products. L-forms are created when mutations that lower ROS levels work in conjunction with enhanced membrane production to allow development without the cell wall. L-forms can multiply without ftsZ (key gene in bacterial cell division) and give rise to asymmetric progeny with different numbers of chromosomes. It should be noted that a monoderm bacteria is depicted in this design. PG, peptidoglycan; IM, inner membrane.