Cell-Wall Recycling of the Gram-Negative Bacteria and the Nexus to Antibiotic Resistance

Abstract

The importance of the cell wall to the viability of the bacterium is underscored by the breadth of antibiotic structures that act by blocking key enzymes that are tasked with cell-wall creation, preservation, and regulation. The interplay between cell-wall integrity, and the summoning forth of resistance mechanisms to deactivate cell-wall-targeting antibiotics, involves exquisite orchestration among cell-wall synthesis and remodeling and the detection of and response to the antibiotics through modulation of gene regulation by specific effectors. Given the profound importance of antibiotics to the practice of medicine, the assertion that understanding this interplay is among the most fundamentally important questions in bacterial physiology is credible. The enigmatic regulation of the expression of the AmpC β-lactamase, a clinically significant and highly regulated resistance response of certain Gram-negative bacteria to the β-lactam antibiotics, is the exemplar of this challenge. This review gives a current perspective to this compelling, and still not fully solved, 35-year enigma.

Corrosion Motivated ROS Generation Helps Endow Titanium with Broad‐Spectrum Antibacterial Abilities

“…The OM is made up of a unique asymmetrical lipid bilayer, with the inner leaflet consisting of phospholipids and the outer leaflet composed by lipopolysaccharide. The OM can act as a barrier to prevent drugs from reaching intracellular targets, rendering the Gram‐ E. coli presents a relatively high resistance to minocycline . Nevertheless, it is reported that the OM is sensitive to ROS .…”

“…Unlike Gram+ species, Gram‐ bacteria lack the thick peptidoglycan cell wall; instead, they possess an additional outer membrane (OM). Most antibiotics can hardly pass through the hydrophobic OM, resulting in their little inhibition effect to Gram‐ bacteria . Therefore, destroying the OM is an effective way to help antibiotics kill Gram‐ bacteria and acquire broad‐spectrum antibacterial abilities .…”

Constructing and deconstructing the bacterial cell wall

“…This scheme is a simplification. Ligand regulation of AmpR is more complex (and indeed, is not general from one bacterial genus to another) as is discussed elsewhere…”

“…The clinical importance of this connection cannot be overstated . The breadth of study of this β‐lactamase‐resistance response—from the molecular (antibiotic structure) to the macromolecular (protein‐ligand interaction, biochemical pathways) to the microbiological and the clinical—requires the medium of the comprehensive review . Here, we focus on the involvement of a family of important enzymes—the lytic transglycosylases—in peptidoglycan recycling and β‐lactamase induction …”

“…[218][219][220] The breadth of study of this β-lactamase-resistance response-from the molecular (antibiotic structure) to the macromolecular (protein-ligand interaction, biochemical pathways) to the microbiological and the clinical-requires the medium of the comprehensive review. [221][222][223][224][225][226][227][228] Here, we focus on the involvement of a family of important enzymes-the lytic transglycosylases-in peptidoglycan recycling and β-lactamase induction. 229,230 The lytic transglycosylases (LTs) are periplasmic enzymes (many, but not all, lipoproteins) that catalyze the deconstruction (hence "lytic") of the polymeric peptidoglycan through the nonhydrolytic cleavage of the glycan strand of the peptidoglycan (hence, the awkward "transglycosylase").…”