So, assuming I'm parsing you correctly, would you say that at this time, the benefit is that we can avoid the bacteria becoming resistant by creating a large range of things that it would have to become resistant to, and the down-side is that since these polypeptides are larger, they will not be as able to be administered where needed? Could this also mean that we end up treating an infection in a specific spot, but allowing it to continue to colonize a different part of the body? For instance, say, in the case of a UTI, where the infection could have moved further up the GI tract, and treatment with polypeptides would work for the urethra, but possibly not further up?
If a particular bacterial strain were to become resistant to a particular bacteriocin, we could use directed evolution methods to modify the bacteriocin.
For example, say the pathogen develops a mutation so that the bacteriocin's binding domain no longer recognizes its bacterial target. Because the bacteriocin is a class of peptide, and not a small molecule, its (theoretically) rather simple to run a directed evolution program in order to discover a variant of the original bacteriocin that will bind the mutant strain. It would be far more difficult to do the same thing with some small molecule antibiotic, and you'd never be able to generate the number of derivatives of the small molecule that you could with a peptide.
Similarly, if the bacteria develops a mutation so that the active domain of the bacteriocin no longer works properly, you can run the same sort of directed evolution experiment.
Or, you could conceivably use a different binding domain altogether as was suggested in the article and in this thread.
As for the delivery of the antibiotic, it needs some way to come in contact with the pathogen. A topical wound that is infected with some form of staphylococcus, for example, could be treated with some sort of ointment. But relying on the body's circulatory system to deliver the drug, well that would seemingly be more difficult than just taking a pill.
