Arming the enemy: the evolution of resistance to self-proteins

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Abstract
A remarkable range of novel antibiotics is attracting increasing interest as a major new weapon in the campaign against bacterial infection. They are based on the toxic peptides that provide the innate immune system of animals, and it is claimed that bacteria will be unable to evolve resistance to them because they attack the ‘Achilles' heel’ of bacterial membrane structure. Both experimental evidence and theoretical arguments suggest that this claim is doubtful. If so, the introduction of these substances into general use may provoke the evolution of resistance to our own defence proteins and thus compromise our natural defences against infection.