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.
Highlights
In all living organisms, the membrane envelope defines the boundary of the cells and serves to protect the cellular content from the external environment
Sen et al used quantification of osmoregulated periplasmic glucans (OPGs) as an indirect method to estimate the Donnan potential (DP) across the outer membrane (OM) of E. coli K-12 (HN455 strain) [42]. They observed that OPGs reduced from 6.5% to 0.5% of the dry weight of bacteria cells as the ionic strength of the external medium increased from 2 mM to 300 mM NaCl
The permeation, distribution, and accumulation of charged antibiotics depend on the synergy among the pH of the external medium, DP across the OM, and the pH gradient across the inner membrane (IM)
Summary
The membrane envelope defines the boundary of the cells and serves to protect the cellular content from the external environment. The periplasm is a unique feature of Gram-negative bacteria and houses a rich collection of small molecule ions, proteins, glucans, and the peptidoglycan scaffold. These components play important roles in structural support, cell division, secretion, envelope stress responding, signaling, and mobility [16,17,18,19]. The OPGs possess multiple net negative charges and are trapped in the periplasm [21,22] Another integrated component of the bacterial cellular envelope, which plays an important role in bacterial drug resistance, is the array of efflux transporters [23,24]. This voltage is less than the estimated 150–200 mV MP across the IM of E. coli [56]
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