Polypeptide variant comprising the sequence as depicted in SEQ ID NO:1, wherein the polypeptide variant comprising the sequence as depicted in SEQ ID NO:1 comprises an endolysin cell binding domain selected from the endolysin CBD of ply_USA as depicted in SEQ ID NO:3 or of ply_pitti20 as depicted in SEQ ID NO:5; or wherein the polypeptide variant comprising the sequence as depicted in SEQ ID NO: 20 or 22; the polypeptide variant further optionally comprising: a) a polypeptide variant comprising the sequence of SEQ ID NO:1 with one or more point mutations or amino acid substitutions in said sequence, (i) wherein the substituted residues are selected from the following amino acid residues of SEQ ID NO:1: F19, W22, W36, F42, Y44, L55, L56, F67, L74, Y78, W107, Y115, I116, Y119, W123, W128, W137, W139, W154, E163, R167, E179, E189, Y200, Y275, Y276, C282, F300 and C303, or (ii) wherein with regard to the sequence of SEQ ID NO:1 the one or more substitutions are selected from the group consisting of: W22R, F42A, F44A F67T, Y115S, W123M, W137A, W139A, W154H, E163A, E179Q, E179A, E187Q, Y200A, Y200H, Y275A, Y275M, Y276A, C282A, F300A, C303S, W310A and W310M, or (iii) wherein one of the following substitutions with regard to SEQ ID NO:1 are selected from the group consisting of: F67T + Y115S, F67T + W137A, F67T + W139A, F67T + W154H, Y115S + W137A, Y115S + W139A, E163Q + R169A, E163A + R169A, E163Q + R167A + E189Q, E163A + R167A + E189Q, E163Q + R167A + E179Q + E189Q, E163Q + R167A + E179A + E189Q, E163A + R167A + E179Q + E189Q, E163A + R167A + E179A + E189Q, Y200A + Y275A, Y200A + Y276A, Y200A + C282A, Y200A + F300A, Y275A + Y276A, L55H + L56T + E163A + R167A + Y200H, E163A + R167A + E179A + E189Q + Y200H, L55H + L56T + E163A + R167A + E179A + E189Q + Y200H, S237L + R354Q + A367V, and L55H + L56T + E163A + R167A + Y200H + S237L + R354Q + A367V, or b) a polypeptide variant comprising in addition to the sequence of SEQ ID NO: 1 sequences representing marker moieties, tags or other functional polypeptide sequences, or c) a polypeptide variant comprising one or more additional amino acid residues inserted into the amino acid sequence according to SEQ ID NO:1 selected from the group consisting of SEQ ID NO: 15, 18, and 28, or d) a polypeptide variant comprising a polypeptide sequence representing any combination of variants a), b), and c). a) a polypeptide variant comprising the sequence of SEQ ID NO:1 with one or more point mutations or amino acid substitutions in said sequence, (i) wherein the substituted residues are selected from the following amino acid residues of SEQ ID NO:1: F19, W22, W36, F42, Y44, L55, L56, F67, L74, Y78, W107, Y115, I116, Y119, W123, W128, W137, W139, W154, E163, R167, E179, E189, Y200, Y275, Y276, C282, F300 and C303, or (ii) wherein with regard to the sequence of SEQ ID NO:1 the one or more substitutions are selected from the group consisting of: W22R, F42A, F44A F67T, Y115S, W123M, W137A, W139A, W154H, E163A, E179Q, E179A, E187Q, Y200A, Y200H, Y275A, Y275M, Y276A, C282A, F300A, C303S, W310A and W310M, or (iii) wherein one of the following substitutions with regard to SEQ ID NO:1 are selected from the group consisting of: F67T + Y115S, F67T + W137A, F67T + W139A, F67T + W154H, Y115S + W137A, Y115S + W139A, E163Q + R169A, E163A + R169A, E163Q + R167A + E189Q, E163A + R167A + E189Q, E163Q + R167A + E179Q + E189Q, E163Q + R167A + E179A + E189Q, E163A + R167A + E179Q + E189Q, E163A + R167A + E179A + E189Q, Y200A + Y275A, Y200A + Y276A, Y200A + C282A, Y200A + F300A, Y275A + Y276A, L55H + L56T + E163A + R167A + Y200H, E163A + R167A + E179A + E189Q + Y200H, L55H + L56T + E163A + R167A + E179A + E189Q + Y200H, S237L + R354Q + A367V, and L55H + L56T + E163A + R167A + Y200H + S237L + R354Q + A367V, or (i) wherein the substituted residues are selected from the following amino acid residues of SEQ ID NO:1: F19, W22, W36, F42, Y44, L55, L56, F67, L74, Y78, W107, Y115, I116, Y119, W123, W128, W137, W139, W154, E163, R167, E179, E189, Y200, Y275, Y276, C282, F300 and C303, or (ii) wherein with regard to the sequence of SEQ ID NO:1 the one or more substitutions are selected from the group consisting of: W22R, F42A, F44A F67T, Y115S, W123M, W137A, W139A, W154H, E163A, E179Q, E179A, E187Q, Y200A, Y200H, Y275A, Y275M, Y276A, C282A, F300A, C303S, W310A and W310M, or (iii) wherein one of the following substitutions with regard to SEQ ID NO:1 are selected from the group consisting of: F67T + Y115S, F67T + W137A, F67T + W139A, F67T + W154H, Y115S + W137A, Y115S + W139A, E163Q + R169A, E163A + R169A, E163Q + R167A + E189Q, E163A + R167A + E189Q, E163Q + R167A + E179Q + E189Q, E163Q + R167A + E179A + E189Q, E163A + R167A + E179Q + E189Q, E163A + R167A + E179A + E189Q, Y200A + Y275A, Y200A + Y276A, Y200A + C282A, Y200A + F300A, Y275A + Y276A, L55H + L56T + E163A + R167A + Y200H, E163A + R167A + E179A + E189Q + Y200H, L55H + L56T + E163A + R167A + E179A + E189Q + Y200H, S237L + R354Q + A367V, and L55H + L56T + E163A + R167A + Y200H + S237L + R354Q + A367V, or b) a polypeptide variant comprising in addition to the sequence of SEQ ID NO: 1 sequences representing marker moieties, tags or other functional polypeptide sequences, or c) a polypeptide variant comprising one or more additional amino acid residues inserted into the amino acid sequence according to SEQ ID NO:1 selected from the group consisting of SEQ ID NO: 15, 18, and 28, or d) a polypeptide variant comprising a polypeptide sequence representing any combination of variants a), b), and c).