Donnan Potential across the Outer Membrane of Gram-Negative Bacteria and Its Effect on the Permeability of Antibiotics

Abstract

The cell envelope structure of Gram-negative bacteria is unique, composed of two lipid bilayer membranes and an aqueous periplasmic space sandwiched in between. The outer membrane constitutes an extra barrier to limit the exchange of molecules between the cells and the exterior environment. Donnan potential is a membrane potential across the outer membrane, resulted from the selective permeability of the membrane, which plays a pivotal role in the permeability of many antibiotics. In this review, we discussed factors that affect the intensity of the Donnan potential, including the osmotic strength and pH of the external media, the osmoregulated periplasmic glucans trapped in the periplasmic space, and the displacement of cell surface charges. The focus of our discussion is the impact of Donnan potential on the cellular permeability of selected antibiotics including fluoroquinolones, tetracyclines, β-lactams, and trimethoprim.

Lipidomics Characterization of the Microbiome in People with Diabetic Foot Infection Using MALDI-TOF MS

“…The balance in the lipid composition of the cell membrane also affects the proper distribution of membrane proteins and, consequently, membrane transport, DNA replication and cell division . Changes in the permeability of the cell membrane resulting from the modification of its structure may be related to the reduced penetration of antibiotics into the cell. …”

“…35 Changes in the permeability of the cell membrane resulting from the modification of its structure may be related to the reduced penetration of antibiotics into the cell. 36 The study used 39 bacterial isolates, which were obtained from superficial swab from 15 patients; 8 species were Grampositive and 7 were Gram-negative bacteria. Figure 1 shows relative amounts of all of the identified obtained lipids from Gram-positive and Gram-negative bacteria.…”

Siderophore‐Linked Ruthenium Catalysts for Targeted Allyl Ester Prodrug Activation within Bacterial Cells

“…Moreover, such prodrugs still possess their secondary amines, which would remain protonated under physiological conditions and thus, might favour passage across the negatively charged outer‐membrane of Gram‐negative bacteria by passive diffusion. In contrast, modification of the C terminus might reduce uptake by porins as coordination to divalent metals such as magnesium is prevented, which have been suggested to improve drug permeability [21] …”

EstG is a novel esterase required for cell envelope integrity

“…The accumulation of charged OPGs attracts counterions to the periplasm, and maintains a Donnan membrane potential across the outer membrane, allowing for isosmolarity of the periplasm and cytoplasm even in low osmolarity environments (Kennedy et al, 1982; Stock et al, 1977). The Donnan potential has also been suggested to play a role in permeability of the envelope to antibiotics (Alegun et al, 2021). These mechanisms, however, presume that OPGs are always highly charged, which is not the case in all bacteria, and may or may not be the case in Caulobacter (Bontemps-Gallo et al, 2017).…”