Membrane, Gram-negative

Gram-positive bacteria contain a rigid peptidoglycan cell wall surrounding the cytoplasmic membrane. Gram-negative bacteria contain an additional third, outer layer. This wall is a complex structure with lipoproteins and lipopolysaccharides. Synthesis of two outer walls from different bacterial cells is described in this concept screen ... 

Because of their extra external membrane. Gram-negative bacteria are accessible to fewer anti-bacterials than Gram-positive organisms. A new attempt to remedy this situation has produced alafosfalin (3.50) which makes use of a peptide permease in this outer membrane to transport the drug into the cell where it is hydrolysed to L-aminoethylphosphonic acid, a potent inhibitor of L-alanine racemase. The normal product of this enzyme, D-alanine, is an... 

Gram-negative organisms produce ced-bound P-lactamases which reside in the periplasmic space. Thus, for gram-negative bacteria, the antibiotic must penetrate the outer ced membrane/wad before coming in contact with a P-lactamase (80,139,140). 

Some polymyxins are sold for second-line systemic therapy. Polymyxin B sulfate and colistimethate sodium can be used for intravenous, intramuscular, or intrathecal administration, especially for Pseudomonas aerupinosa mP QXiosis, but also for most other gram-negative organisms, such as those resistant to first-line antibiotics. Nephrotoxicity and various neurotoxicities are common in parenteral, but not in topical, use. Resistance to polymyxins develops slowly, involves mutation and, at least in some bacteria, adaptation, a poorly understood type of resistance that is rapidly lost on transfer to a medium free of polymyxin. Resistance can involve changes in the proteins, the lipopolysaccharides, and lipids of the outer membrane of the cell (52). Polymyxin and colistin show complete cross-resistance. 

Gram-negative bacteria are surrounded by two membranes, an inner plasma membrane and an outer membrane. These are separated by a periplasmic space. Most plasma membrane proteins contain long, continuous sequences of about 20 hydrophobic residues that are typical of transmembrane a helices such as those found in bacteriorhodopsin. In contrast, most outer membrane proteins do not show such sequence patterns. 

As shown in Figure 9.24, the outer membrane of Gram-negative bacteria is coated with a highly complex lipopolysaccharide, which consists of a lipid group (anchored in the outer membrane) joined to a polysaccharide made up of long chains with many different and characteristic repeating structures... 

Source Adapted, from Benz, R., 1984. Sti ucture and selecdvity of porin channels. Current Topics in Membrane TrawsjiJorf 21 199-219 and Benz, R., 1988. Sti ucture and function of porins from Gram-negative bacteria. Annual Review of Microbiology 42 359-393. 

Polymyxin B Bacillus polymyxa Gram-negative bacteria Cell membrane... 

Currently, five different molecular classes of mdr efflux pumps are known [5], While pumps of the the ATP-binding cassette (ABC) transporter superfamily are driven by ATP hydrolysis, the other four superfamilies called resistance-nodulation-division (RND), major facilitator superfamily (MFS), multidrug and toxic compound extrusion (MATE), and small multidrag resistance transporter (SMR) are driven by the proton-motive force across the cytoplasmic membrane. Usually a single pump protein is located within the cytoplasmic membrane. However, the RND-type pumps which are restricted to Gram-negative bacteria consist of two additional components, a periplasmic membrane fusion protein (MFP) which connects the efflux pump to an outer... 

Endotoxins are the lipopolysaccharides (LPS) of the outer membrane of Gram-negative bacteria. They trigger inflammatory reactions in the infected organism, activate complement and cause fever or even a septic shock. They act on toll-like receptors. 

In Gram-negative bacteria, diffusion of (3-lactam antibiotics into the periplasm (where the activity of PBPs takes place) occurs via the channels that porins create in the outer membrane. The number and properties of the porin molecules are such that diffusion is relatively rapid in E. coli but much slower in Enterobacter and Pseudomonas. Mutants can be selected after the permeability of porin channels or their number has been decreased. A slow diffusion into... 

The outer membrane of gram-negative bacteria is a permeability barrier that allows the passive diffusion of small hydrophilic antibiotics only through aqueous channels, the porins. Drugs larger than 800 Da are... 

The complex outer layers beyond the peptidoglycan in the Gram-negative species, the outer membrane, protect the organism to a certain extent from the action of toxic chemicals (see Chapter 13). Thus, disinfectants are often effective only at concentrations higher than those affecting Gram-positive cells and these layers provide unique protection to the cells from the action of benzylpenicillin and lysozyme. 

---