The present invention relates to novel methods of generating and screening for chimeric polypeptides, which can be used in the treatment and prophylaxis of pathogenic bacterial contamination, colonization and infection. The novel methods are based on random recombination of protein domains, and the chimeric polypeptides obtainable by the methods according to the invention are characterized in that they comprise at least one enzymatic active domain (EAD) and at least one cell binding domain (CBD). The present invention also relates to a library of chimeric polypeptides obtainable by the methods of the present invention.