Abstract: Disclosed are novel lysin polypeptides active against Gram-negative bacteria, particularly P. aeruginosa, pharmaceutical compositions containing them and methods for their use to treat Gram-negative bacterial infections and more generally to inhibit the growth, or reduce the population, or kill Gram-negative bacteria, including without limitation disrupting biofilms formed by such bacteria. Certain of the disclosed lysins have been modified in amino acid sequence compared to that of lysins by replacement of certain charged amino acids with noncharged amino acids and/or by fusion at the N- or C-terminus with antibacterial peptide sequences with or without an intervening linker.

Abstract: Disclosed herein are modified lysin polypeptides thereof comprising at least one amino acid substitution as compared to a wild-type PlySs2 lysin polypeptide having an amino acid sequence of SEQ ID NO: 1, wherein the at least one amino acid substitution is in the CHAP domain and/or the SH3b domain, and wherein the modified lysin polypeptide or fragment thereof inhibits the growth, tin reduces the population, or kills at least one species of Gram-positive bacteria. Further disclosed herein are compositions comprising the modified lysin polypeptides, as well as vectors comprising a nucleic acid molecule that encodes the modified lysin polypeptide. Also disclosed herein are methods of inhibiting the growth, reducing the population, or killing at least one species of Gram-positive bacteria, methods of treating a bacterial infection, and methods of augmenting the efficacy of an antibiotic or reducing the development of antibiotic resistance.