Outer membrane factor

The RND family of efflux pumps are restricted to gram-negative organisms and consists of three major components the RND pump, a periplasmic membrane fusion protein (MFP), and an outer-membrane factor (OMF). Together these three proteins are able to effectively pump a variety of antibiotics, dyes, and ions depending on the type of RND pump associated with the system (Figure 3.2). The... 

Figure 3.2. A representative RND efflux pump system. This system is comprised of three essential components The RND pump (e.g., AcrD and MexX) is located on the cytoplasmic membrane and is responsible for the recognition of substrates in the cytosol, including aminoglycosides, and moving them into the periplasmic space. The membrane fusion protein (MFP) (e.g., AcrA and MexY) is responsible for moving the substrate across the periplasm the final component is the outer membrane factor (OMF) (e.g., TolC and OprM) that provides a conduit for the substrate to the extracellular region of the cell.

Resistance. Resistance to the cephalosporins may result from the alteration of target pencillin-binding sites (PBPs), decreased permeabdity of the bacterial ced wad and outer membrane, or by inactivation via enzyme mediated hydrolysis of the lactam ring (80,81,138—140). This resistance can be either natural or acquired. Although resistance is often attributed speciftcady to one of these factors, in reaUty it reflects the interplay of several factors. In most instances, however, resistance results from the production of a P-lactamase enzyme, which opens the P-lactam ring as depicted in Figure 2. 

The current functional model of o control is depicted in Fig. 2. In the absence of non-native proteins in the periplasm or outer membrane, o is sequestered by RseA acting as an anti-sigma factor. Tight binding of o requires the participation of RseB which might act as an co-anti-sigma factor. Upon accumulation of non-native proteins outside the cytoplasm, RseB is released from... 

Burkholderia (formeriy Pseudomonas) cepacia is intrinsically resistant to a number of biocides, notably benzalkonium chloride and chlorhexidine. Again, the outer membrane is likely to act as a permeability barrier. By contrasL Ps. stutzeri (an organism implicated in eye infections caused by some cosmetic products) is invariably intrinsically sensitive to a range of biocides, including QACs and chlorhexidine. This organism contains less wall muramic acid than other pseudomonads but it is imclear as to whether this could be a contributory factor in its enhanced biocide susceptibility. 

LPS, the immunoactive component of endotoxin, is a constituent of the outer membrane of Gram-negative bacterial cell walls. LPS is found in the environment and has been extensively studied, both as a mediator of inflammation and as a major contributing factor to bacterial pathogenesis.60 LPS exerts many of its effects through induction of pro-inflammatory cytokines, including IL-ip, TNF-a and IL-6.61 An important feature... 

It appears that qualitative correlations between antibacterial activity and rate constants of HO ion catalyzed hydrolysis are fortuitous since many factors other than transpeptidase acylation contribute to antimicrobial activity. These other contributing factors include permeation of the outer membrane of the bacterial cell wall, resistance to /3-lactamase, the fit in the active site of the enzyme, stability of the acylated enzyme, and, last but not least, in vivo pharmacokinetic behavior. 

U. Hechler, M. Van Den Weghe, H. H. Martin, J. M. Frere, Overproduced /3-Lactamase and the Outer Membrane Barrier as Resistance Factors in Serratia marcesens Highly Resistant to /3-Lactamase Stable /3-Lactam Antibiotics , J. Gen. Microbiol. 1989, 135, 1275-1290. 

Figure 5.1 Growth factor receptors are illustrated here. Docking proteins—receptors for protein growth factors—are embedded in the outer membranes of cells. Binding of the specific growth factor triggers a cascade of biochemical signals that cause the cell to divide and express the proteins that give the cell specialized properties.

A major factor controlling the oxidation of fatty acids is the rate of entry into the mitochondria. While some long-chain fatty acids (perhaps 30% of the total) enter mitochondria as such and are converted to CoA derivatives in the matrix, the majority are "activated" to acyl-CoA derivatives on the inner surface of the outer membranes of the mitochondria. Penetration of these acyl-CoA derivatives through the mitochondrial inner membrane is facilitated by L-camitine 41 44... 

Cytochrome c (Cyt c), the peripheral protein loosely associated with the inner membrane of mitochondria, is one of the most well-known factors involved in apoptosis (Green 2005). In healthy cells, Cyt c functions as an electron shuttle in the respiratory chain and its activity is necessary for life. Cyt c is released by the mitochondria as the consequence of elevated permeability of the outer membrane in responses to proapoptotic stimuli (Li et al. 1997). In the cytosol, Cyt c binds to the apoptosis-protease activating factor 1 (Apaf-1), which then recruits caspase-9 to form the apoptosome (Li et al. 1997). Caspase-9 in turn cleaves and activates executioner caspase-3, resulting in apoptotic cell death as described above. The whole process requires energy and relatively intact cell machinery. 

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