Barrier properties of the Gram-negative cell envelope towards high molecular weight polyhexamethylene biguanides

G ilbert , P., P emberton , D. & W ilkinson , D.E. 1990. Barrier properties of the Gram-negative cell envelope towards high molecular weight polyhexamethylene biguanides. Journal of Applied Bacteriology 69 , 585–592.
The antimicrobial activities of four discrete molecular weight fractions of polyhexamethylene biguanides towards a number of Escherichia coli strains have been investigated. Whilst activity of the polymers was observed to increase in proportion to polymerization number, the dependence of activity upon molecular weight was five times greater towards sphaeroplasts than towards whole cells. This suggested that the cell envelope, whilst not conferrring complete resistance to the agents, did provide a significant exclusion barrier. Comparison of the activities towards rough and deep-rough lipopolysaccharide strains showed growth inhibitory activity, but not bactericidal activity nor respiratory inhibition, to be enhanced in the rough strains. Uptake studies showed mixed H- and C-type adsorption with significantly greater numbers of high-affinity binding sites being associated with rough than deep-rough lipopolysaccharide. The binding affinity of polyhexamethylene biguanides towards cells was also enhanced in the rough strains. Binding affinity was, in all cases, significantly reduced in the presence of magnesium and suggested a mechanism of self-promoted uptake for these biocides, facilitated through core lipopolysaccharide.     

Neuronal cell life,death, and axonal degeneration as regulated by the BCL-2 family proteins

Axonal degeneration and neuronal cell death are fundamental processes in development and contribute to the pathology of neurological disease in adults. Both processes are regulated by BCL-2 family proteins which orchestrate the permeabilization of the mitochondrial outer membrane (MOM). MOM permeabilization (MOMP) results in the activation of pro-apoptotic molecules that commit neurons to either die or degenerate. With the success of small-molecule inhibitors targeting anti-apoptotic BCL-2 proteins for the treatment of lymphoma, we can now envision the use of inhibitors of apoptosis with exquisite selectivity for BCL-2 family protein regulation of neuronal apoptosis in the treatment of nervous system disease. Critical to this development is deciphering which subset of proteins is required for neuronal apoptosis and axon degeneration, and how these two different outcomes are separately regulated. Moreover, noncanonical BCL-2 family protein functions unrelated to the regulation of MOMP, including impacting necroptosis and other modes of cell death may reveal additional potential targets and/or confounders. This review highlights our current understanding of BCL-2 family mediated neuronal cell death and axon degeneration, while identifying future research questions to be resolved to enable regulating neuronal survival pharmacologically.Subject terms: Cell biology, Chemical tools, Neuroscience, Neurological disorders