The present invention relates to chimeric polypeptides comprising a first portion, which comprises a bacteriocin cell wall-binding domain (CBD) and a second portion, which comprises an enzymatic active domain (EAD) selected from the lytic domain of a bacteriophage lysin, a bacteriocin and a bacterial autolysin. Provided are such chimeric polypeptides and variants and fragments thereof, nucleic acids encoding the same, vectors carrying such nucleic acids and host cells transformed or transfected with such vectors. The chimeric polypeptides of the present invention are useful for the reduction of certain bacterial populations, including methods and compositions for the treatment of various bacterial infections. For example, chimeric polypeptides of the present invention have been shown to effectively kill various bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), as well as other human pathogens. Thus, provided are compositions comprising chimeric polypeptides according to the present invention, variants or fragments thereof, and the use of such compositions in prophylaxis or therapy of bacterial diseases, bacterial infections or bacterial colonizations.