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      Protein Antibiotics - How they work - BBSRC - Wellcome Trust

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          Abstract

          Gram-negative bacteria are surrounded by two membranes, the outer most of which (usually referred to as the 'outer membrane') is a highly effective barrier against toxic molecules; for example, bile salts which exist within the gut of a mammal. The effectiveness of the outer membrane is a double-edged sword for the organism since it is also very effective at keeping out essential nutrients such as sugars, which the organism needs to grow and divide. Hence all organisms that have an outer membrane also have specialised proteins within this membrane whose job it is to allow the exchange of nutrients and metabolites with the environment. These proteins are known as porins, which are barrel-like membrane proteins that have a hole or pore running through them which traverses the membrane. There are many barrel proteins in the outer membrane of Gram-negative bacteria (it is estimated that 2-3% of the E. coli genome encode such proteins) which serve a variety of functions. Those that allow the exchange of nutrients are usually referred to as general or classical porins, the best understood of which are the proteins OmpF and OmpC. These porins are also the major routes by which commonly used antibiotics (e.g. ampicillin) diffuse into the cell. Indeed, the channels of these porins are frequently found to be mutated in multidrug resistant bacteria. Moreover, porin channels are increasingly understood to be the route by which antibacterial peptides and possibly even proteins penetrate and kill Gram-negative bacteria. Antibacterial proteins known as bacteriocins allow bacteria to engage in 'bacterial warfare' whereby they kill their immediate neighbours when faced with competition for nutrients and other resources. The Kleanthous group has demonstrated how bacteriocins exploit porins to help them get across the outer membrane and, in association with laboratories around the UK, is leading efforts to help develop these toxins as antibiotics of the future.

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          Journal
          Impact
          impact
          Science Impact, Ltd.
          2398-7073
          August 08 2017
          August 08 2017
          : 2017
          : 6
          : 45-47
          Article
          10.21820/23987073.2017.6.45
          © 2017

          This work is licensed under a Creative Commons Attribution 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

          Earth & Environmental sciences, Medicine, Computer science, Agriculture, Engineering

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