ANTIMICROBIAL AGENTS AGAINST SALMONELLA BACTERIA

Abstract

The present invention relates to the field of antimicrobial agents active against Salmonella bacteria. In particular, the present invention relates to polypeptides comprising a first and a second amino acid sequence, wherein the first amino acid sequence is an endolysin, and wherein the second amino acid sequence is an antimicrobial peptide, cationic peptide, hydrophobic peptide, amphipathic peptide or sushi peptide, and wherein the polypeptide comprises at least one sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4 and derivatives thereof. In addition, the present invention relates to nucleic acids encoding such polypeptides, vectors comprising such nucleic acids, and corresponding host cells. Finally, the present invention relates to applications of the inventive polypeptides, nucleic acids, vectors, and/or host cells, in particular in the pharmaceutical field and in the field of food and feed.

Claims

1. A polypeptide comprising a first and a second amino acid sequence, wherein the first amino acid sequence is an endolysin, and wherein the second amino acid sequence is an antimicrobial peptide, cationic peptide, hydrophobic peptide, amphiphatic peptide or sushi peptide, and wherein the polypeptide comprises at least one sequence selected from the following group of sequences: i) an amino acid sequence according to SEQ ID NO: 1; ii) a derivative of SEQ ID NO: 1 exhibiting at least 80% sequence identity with SEQ ID NO: 1, with the proviso that the polypeptide may not comprise the sequence of SEQ ID NO:5, if the polypeptide comprises ii), but none of iii), iv), v) or vi), iii) an amino acid sequence according to SEQ ID NO:3; iv) a derivative of SEQ ID NO:3 exhibiting at least 77% sequence identity with SEQ ID NO:3; v) an amino acid sequence according to SEQ ID NO:4; with the proviso that the polypeptide may in this case not comprise the sequence of SEQ ID NO:6 in parallel; and vi) a derivative of SEQ ID NO:4 exhibiting at least 80% sequence identity with SEQ ID NO:4.

2. The polypeptide according to claim 1, wherein the first amino acid sequence is selected from the group consisting of: i) an amino acid sequence according to SEQ ID NO: 1; ii) a derivative of SEQ ID NO: 1 exhibiting at least 80% sequence identity with SEQ ID NO:1, iii) an amino acid sequence according to SEQ ID NO:2; and iv) a derivative of SEQ ID NO:2 exhibiting at least 80% sequence identity with SEQ ID NO:2.

3. The polypeptide according to claim 2, wherein the derivative of SEQ ID NO:2 exhibits at least 85%, at least 87.5%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or more than 99% sequence identity with SEQ ID NO:2.

4. The polypeptide according to claim 2, wherein said derivative of SEQ ID NO:2 comprises a sequence according to SEQ ID NO:8, in particular wherein said derivative comprises a sequence according to SEQ ID NO: 13.

5. The polypeptide according to claim 1, wherein the derivative of SEQ ID NO:1 exhibits at least 85%, at least 87.5%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or more than 99% sequence identity with SEQ ID NO: 1.

6. The polypeptide according to claim 1, wherein the derivative of SEQ ID NO:1 exhibits at least 98%, at least 99%, or more than 99% sequence identity with SEQ ID NO: 1.

7. The polypeptide according to claim 1, wherein the derivative of SEQ ID NO: 1 is an amino acid sequence according to SEQ ID NO:7.

8. The polypeptide according to claim 1, wherein the second amino acid sequence is selected from the group consisting of: i) an amino acid sequence according to SEQ ID NO:3; ii) a derivative of SEQ ID NO:3 exhibiting at least 77% sequence identity with SEQ ID NO:3; iii) an amino acid sequence according to SEQ ID NO:4; and iv) a derivative of SEQ ID NO:4 exhibiting at least 80% sequence identity with SEQ ID NO:4.

9. The polypeptide according to claim 8, wherein the derivative of SEQ ID NO:3 exhibits at least 81%, at least 86%, at least 90%, or at least 95% sequence identity with SEQ ID NO:3, or wherein the derivative of SEQ ID NO:4 exhibits at least 83%, at least 86%, at least 90%, at least 93%, or at least 96% sequence identity with SEQ ID NO:4.

10. The polypeptide according to claim 1, wherein the polypeptide comprises an amino acid sequence according to SEQ ID NO:4; but does not comprise the amino acid sequence according to SEQ ID NO:2.

11. The polypeptide according to claim 1, wherein the first amino acid sequence is SEQ ID NO:1 or said derivative thereof, and wherein the second amino acid sequence is SEQ ID NO:3 or said derivative thereof, or wherein the first amino acid sequence is SEQ ID NO:1 or said derivative thereof, and wherein the second amino acid sequence is SEQ ID NO:4 or said derivative thereof, or wherein the first amino acid sequence is SEQ ID NO:2 or said derivative thereof, and wherein the second amino acid sequence is SEQ ID NO:3 or said derivative thereof or wherein the first amino acid sequence is SEQ ID NO:2, and wherein the second amino acid sequence is said derivative of SEQ ID NO:4, or wherein the first amino acid sequence is said derivative of SEQ ID NO:2, and wherein the second amino acid sequence is SEQ ID NO:4 or said derivative thereof.

12. The polypeptide according to claim 1, wherein said derivative of SEQ ID NO:3 is a fragment of SEQ ID NO:3, in particular a fragment according to SEQ ID NO:37.

13. The polypeptide according to claim 1, wherein i) the first amino acid sequence is SEQ ID NO: 1 and the second amino acid sequence is SEQ ID NO:3, ii) the first amino acid sequence is SEQ ID NO: 1 and the second amino acid sequence is SEQ ID NO:4, iii) the first amino acid sequence is SEQ ID NO: 13 and the second amino acid sequence is SEQ ID NO:3, or iii) wherein the first amino acid sequence is SEQ ID NO:13 and the second amino acid sequence is SEQ ID NO:4.

14. The polypeptide according to claim 13, wherein the polypeptide comprises an amino acid sequence according to SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 135 or SEQ ID NO: 136.

15. The polypeptide according to claim 1, wherein the polypeptide comprises an amino acid sequence as encoded by a nucleic acid sequence according to SEQ ID NO:153 or according to SEQ ID NO:154.

16. The polypeptide according to claim 1, wherein the polypeptide degrades the peptidoglycan of Salmonella bacteria.

17. A nucleic acid encoding a polypeptide according to claim 1.

18. A vector comprising a nucleic acid according to claim 17.

19. A host cell comprising a nucleic acid according to claim 17.

20. A composition comprising a polypeptide according to claim 1.

21. The composition according to claim 20, wherein the composition is a pharmaceutical composition comprising a pharmaceutical acceptable diluent, excipient or carrier.

22. (canceled)

23. A method of treating or preventing infections caused by bacteria of the genus Salmonella comprising administering to a subject in need thereof a polypeptide, a nucleic acid encoding said polypeptide, or a vector comprising said nucleic acid encoding said polypeptide, wherein the polypeptide comprises a first and a second amino acid sequence, wherein the first amino acid sequence is an endolysin, and wherein the second amino acid sequence is an antimicrobial peptide, amphiphatic peptide, cationic peptide, hydrophobic peptide, sushi peptide or defensin, and wherein the polypeptide comprises at least one sequence selected from the following group of sequences: i) an amino acid sequence according to SEQ ID NO: 1; ii) a derivative of SEQ ID NO:1 exhibiting at least 80% sequence identity with SEQ ID NO:1, iii) an amino acid sequence according to SEQ ID NO:2; iv) a derivative of SEQ ID NO:2 exhibiting at least 80% sequence identity with SEQ ID NO:2, v) an amino acid sequence according to SEQ ID NO:3; vi) a derivative of SEQ ID NO:3 exhibiting at least 77% sequence identity with SEQ ID NO:3; vii) an amino acid sequence according to SEQ ID NO:4; and viii) a derivative of SEQ ID NO:4 exhibiting at least 80% sequence identity with SEQ ID NO:4.

24-25. (canceled)

26. A method of controlling the growth of bacteria of the genus Salmonella in animals, in particular in livestock, companion animal and/or aquaculture, the method comprising contacting said animal, in particular the livestock, companion animal and/or aquaculture, with a polypeptide, a nucleic acid encoding such polypeptide, a vector comprising such nucleic acid, a host cell comprising such polypeptide, nucleic acid and/or vector, or a composition comprising such polypeptide, nucleic acid, vector, and/or host cell, wherein the polypeptide comprises a first and a second amino acid sequence, wherein the first amino acid sequence is an endolysin, and wherein the second amino acid sequence is an antimicrobial peptide, amphiphatic peptide, cationic peptide, hydrophobic peptide, sushi peptide or defensin, and wherein the polypeptide comprises at least one sequence selected from the following group of sequences: i) an amino acid sequence according to SEQ ID NO: 1; ii) a derivative of SEQ ID NO: 1 exhibiting at least 80% sequence identity with SEQ ID NO:1, iii) an amino acid sequence according to SEQ ID NO:2; iv) a derivative of SEQ ID NO:2 exhibiting at least 80% sequence identity with SEQ ID NO:2, v) an amino acid sequence according to SEQ ID NO:3; vi) a derivative of SEQ ID NO:3 exhibiting at least 77% sequence identity with SEQ ID NO:3; vii) an amino acid sequence according to SEQ ID NO:4; and viii) a derivative of SEQ ID NO:4 exhibiting at least 80% sequence identity with SEQ ID NO:4.

27. The method according to claim 26, wherein the polypeptide is a polypeptide according to claim 1.

Description

EXAMPLES

[0147] In the following, specific examples illustrating various embodiments and aspects of the invention are presented. However, the present invention shall not to be limited in scope by the specific embodiments described herein. Indeed, various modifications of the invention in addition to those described herein will become readily apparent to those skilled in the art from the foregoing description, accompanying figures and the examples below. All such modifications fall within the scope of the appended claims.

Example 1: Data on Antibacterial Activity on S. Typhimurium LT2 from Prior Art Polypeptides Published in Briers et al, MBio. 2014 Jul. 1:5(4):e01379-14

[0148] Briers et al. published antibacterial activity of various fusion proteins for S. Typhimurium LT2 (see supplemental table 5). The data are summarized in table 3 (fusion variants of endolysin OBPgp279) and in table 4 (fusion variants of endolysin PVP-SE1gp146).

TABLE-US-00003 TABLE 3 Fusion variants of endolysin OBPgp279 Fusion Polypeptide w/o EDTA 0.5 mM EDTA 0.05 0.05 PCNP LoGT-001 0.23 0.03 0.91 0.04 MW1 LoGT-002 0.15 0.07 0.41 0.08 HPP LoGT-003 0.09 0.01 0.52 0.04 MW2 LoGT-004 0.12 0.06 0.36 0.07 .sub.4 LoGT-005 0.17 0.08 0.43 0.09 Parasin1 LoGT-006 0.20 0.14 0.60 0.05 Lycotoxin1 LoGT-007 0.01 0.11 0.51 0.04

TABLE-US-00004 TABLE 4 Fusion variants of endolysin PVP-SE1gp146 S. Typhimurium Fusion Polypeptide LT2 0.5 mM EDTA 0.05 0.05 PCNP LoGT-008 0.30 0.10 0.73 0.30 MW1 LoGT-009 0.10 0.07 0.27 0.15 HPP LoGT-010 0.24 0.16 0.47 0.07 MW2 LoGT-011 0.12 0.12 0.41 0.25 .sub.4 LoGT-012 0.14 0.12 0.47 0.24 Parasin1 LoGT-013 0.04 0.03 0.59 0.38 Lycotoxin1 LoGT-014 0.20 0.22 0.87 0.28

Example 2: Data on Antibacterial Activity of Selected Inventive Polypeptides on S. Typhimurium LT2

[0149] The inventors of the present invention have tested antibacterial activity of polypeptides comprising SEQ ID NO: 126 or SEQ ID NO: 129 (and further comprising a His-tag for purification reasons) on S. Typhimurium LT2. A first set of experiments was conducted in PBS buffer.

[0150] Briefly, exponentially growing cells of Salmonella Typhimurium LT2 were diluted 1:100 in 5 mM HEPES pH 7.4. Subsequently, 100 l of cells were incubated for 30 min at room temperature with 50 l protein solution dissolved in 1PBS (170 mM NaCl, 3 mM KCl, 12.7 mM Na.sub.2HPO.sub.4, 2.2 mM KH.sub.2PO.sub.4, pH 7.4) and 50 l of 5 mM HEPES pH 7.4 or 50 L of EDTA (final concentration 0.5 mM) yielding a final protein concentration of 1.313 M. Cells were serially diluted in 1PBS after incubation and plated on LB agar. As a negative control, cells were incubated in the same buffer without any protein and additionally plated. Cell colonies were counted after incubation over night at 37 C. and the antibacterial activity was calculated in logarithmic units (=log 10No/Ni with N0=number of untreated colonies and Ni=number of treated colonies).

[0151] The results are shown in table 5 below.

TABLE-US-00005 TABLE 5 Antibacterial activity of inventive polypeptides in PBS buffer SEQ ID NO w/o EDTA 0.5 mM EDTA SEQ ID NO: 126 2.75 4.00 SEQ ID NO: 129 1.61 2.29

[0152] In a further set of experiments, antibacterial activity in HEPES-buffer on S. Typhimurium LT2 was determined.

[0153] Briefly, exponentially growing cells of Salmonella Typhimurium LT2 were diluted 1:100 in 5 mM HEPES pH 7.4. Subsequently, 100 l of cells were incubated for 30 min at room temperature with 50 l protein solution dissolved in 20 mM HEPES, 500 mM NaCl pH 7.4 and 50 l of 5 mM HEPES pH 7.4 or 50 L of EDTA (final concentration 0.5 mM) yielding a final protein concentration of 1.313 M. Cells were serially diluted in 1PBS after incubation and plated on LB agar. As a negative control, cells were incubated in the same buffer without any protein and additionally plated. Cell colonies were counted after incubation over night at 37 C. and the antibacterial activity was calculated in logarithmic units (=log 10No/Ni with N0=number of untreated colonies and Ni=number of treated colonies).

[0154] The results are shown in table 6 below.

TABLE-US-00006 TABLE 6 Antibacterial activity of inventive polypeptides in HEPES buffer SEQ ID NO w/o EDTA 0.5 mM EDTA SEQ ID NO: 126 0.95 3.62 SEQ ID NO: 129 1.24 1.61

[0155] In summary, antibacterial activity of the inventive polypeptides comprising the amino acids sequence of SEQ ID NO: 126 or SEQ ID NO: 129 on S. Typhimurium LT2 surprisingly exceeded the antibacterial activity achieved with similar compounds in the art significantly.

Example 3: Data on Antibacterial Activity of Further Inventive Polypeptides on S. Typhimurium LT2

[0156] In another set of experiments, the inventors of the present invention have also tested antibacterial activity of further fusion proteins comprising the components of the polypeptides of the present invention. The polypeptides tested did comprise the sequences of SEQ ID NO: 138, SEQ ID NO: 141, SEQ ID NO: 132, SEQ ID NO: 144, and SEQ ID NO: 147 (and further comprising a His-tag for purification reasons) and were tested on S. Typhimurium LT2. The tested compounds all comprise at least one component which can be advantageously used according to the present invention (SEQ ID NO:1, SEQ ID NO:3 and (SEQ ID NO:4) for treating in particular Salmonella bacteria.

[0157] The experiment was done as set out in Example 2.

[0158] The results are shown in table 7 below.

TABLE-US-00007 TABLE 7 Antibacterial activity of inventive polypeptides in HEPES buffer SEQ ID NO w/o EDTA 0.5 mM EDTA SEQ ID NO: 138 0.76 0.88 SEQ ID NO: 141 1.71 1.47 SEQ ID NO: 132 2.74 >5 SEQ ID NO: 144 0.15 3.24 SEQ ID NO: 147 0.33 0.98

[0159] In summary, antibacterial activity of the inventive polypeptides comprising the amino acids sequence of SEQ ID NO: 138, SEQ ID NO: 141, SEQ ID NO: 132, SEQ ID NO: 144, and SEQ ID NO: 147 on S. Typhimurium LT2 reliably exceeded the antibacterial activity achieved with similar compounds in the art, indicating that the components used (SEQ ID NO:1, SEQ ID NO:3 and SEQ ID NO:4) all can provide for superior activity against Salmonella bacteria in comparison to the compounds of the prior art. Noteworthy, the polypeptide comprising two components of the invention (SEQ ID NO: 132) yielded again by far the best results.

Example 4: Data on Antibacterial Activity of Selected Inventive Polypeptide on S. Typhimurium (DSM 17058)

[0160] The inventors of the present invention have tested antibacterial activity of an inventive polypeptide comprising SEQ ID NO: 135 (and further comprising a His-tag for purification reasons) on S. Typhimurium (DSM 17058).

[0161] The experiment was done as set out in Example 2.

[0162] The results are shown in table 8 below.

TABLE-US-00008 TABLE 8 Antibacterial activity of inventive polypeptides in HEPES buffer SEQ ID NO w/o EDTA 0.5 mM EDTA SEQ ID NO: 135 3.91 3.88

[0163] Hence, antibacterial activity of the inventive polypeptide comprising the amino acid sequence of SEQ ID NO: 135 on S. Typhimurium (DSM 17058) exceeded the antibacterial activity achieved with similar compounds in the art, indicating that the endolysin component used (SEQ ID NO: 13) provides for superior activity against Salmonella bacteria in comparison to the respective components of the prior art polypeptides (i.e. endolysin components OBPgp279 and PVP-SE1gp146).

Example 5: Data on Minimal Inhibitory Concentration of Selected Inventive Polypeptide on S. Typhimurium (DSM 17058)

[0164] The inventors of the present invention have tested antibacterial activity in terms of minimal inhibitory concentration (MIC) of an inventive polypeptide comprising SEQ ID NO: 132 (and further comprising a His-tag for purification reasons) on S. Typhimurium (DSM 17058).

[0165] Briefly, Bacteria were grown in (Luria-Bertani) medium and diluted 1:10 in Mueller-Hinton medium. At optical density OD.sub.600 of about 0.6 bacteria were diluted in the same medium 1:10 followed by a 1:500 dilution in the same medium. Protein solutions were pipetted into a 96 well plate, using different concentrations of proteins and an end volume of 20 l including 500 M EDTA final concentration. 180 l of bacterial cells or a medium (Mueller-Hinton) control were given to the 96 well plate and mixed. The plate was incubated for 18-22 hours at 37 C. and the bacterial growth was determined measuring the OD.sub.600 values of the wells. The MIC which is the protein concentration of the well which showed the same OD.sub.600 value as determined for the no-bacteria control.

[0166] The results in form of minimal inhibitory concentration (MIC) are shown in table 9 below.

TABLE-US-00009 TABLE 9 Antibacterial activity of inventive polypeptides in PBS buffer SEQ ID NO 0.5 mM EDTA SEQ ID NO: 132 5

Example 6: Data on Antibacterial Activity of Selected Inventive Polypeptide on Various Salmonella Enteritidis Serovars in Presence of Salt

[0167] The inventors of the present invention have tested antibacterial activity of the polypeptide comprising SEQ ID NO: 132 (and further comprising a His-tag for purification reasons) on various Salmonella serovars in presence of physiological salt levels.

[0168] Briefly, exponentially growing cells of Salmonella Enteritidis were diluted 1:10 in 20 mM HEPES pH 7.4, 150 mM NaCl. Subsequently, 50 l of cells were incubated for 1 h at 37 C. with 50 l protein solution dissolved in 20 mM HEPES, 150 mM NaCl pH 7.4 yielding a final protein concentration of 100 g/ml. Cells were serially diluted in 1PBS after incubation and plated on LB agar. As a negative control, cells were incubated in the same buffer without any protein and additionally plated. Cell colonies were counted after incubation over night at 37 C. and the antibacterial activity was calculated in logarithmic units (=log 10No/Ni with N0=number of untreated colonies and Ni=number of treated colonies).

[0169] The results in form of minimal inhibitory concentration (MIC) are shown in table 10 below.

TABLE-US-00010 TABLE 10 Antibacterial activity of inventive polypeptides under physiological conditions SEQ ID NO Serovar w/o EDTA SEQ ID NO: 132 Salmonella Enteritidis RKI 3.5 14-00409 SEQ ID NO: 132 Salmonella Enteritidis 4.5-5.5 LGL-246 SEQ ID NO: 132 Salmonella Enteritidis 6 29/2014

[0170] The polypeptide comprising SEQ ID NO: 132 thus shows significant antibacterial activity in presence of physiological salt conditions.

Example 7: Thermostability

[0171] The inventors of the present invention have tested antibacterial activity of the polypeptide comprising SEQ ID NO: 126 on S. Typhimurium (DSM 17058) with increasing temperatures.

[0172] Briefly, prior to the determination of the MIC, the protein solution is heated to given temperatures for 20 min. Subsequently, the protein solution is stored on ice to reach a temperature of 4 C. Bacteria were grown in (Luria-Bertani) medium and diluted 1:10 in Mueller-Hinton medium. At optical density OD.sub.600 of about 0.6 bacteria were diluted in the same medium 1:10 followed by a 1:500 dilution in the same medium. Protein solutions were pipetted into a 96 well plate, using different concentrations of proteins and an end volume of 20 l including 500 M EDTA final concentration. 180 l of bacterial cells or a medium (Mueller-Hinton) control were given to the 96 well plate and mixed. The plate was incubated for 18-22 hours at 37 C. and the bacterial growth was determined measuring the OD.sub.600 values of the wells. The MIC which is the protein concentration of the well which showed the same OD.sub.600 value as determined for the no-bacteria control.

[0173] The results in form of minimal inhibitory concentration (MIC) are shown in table 11 below.

TABLE-US-00011 TABLE 11 Antibacterial activity of inventive polypeptide with increasing temperature MIC [g/ml] SEQ ID NO: Temp. [ C.] 126 RT 6 70 12 74 10 78 10 82 10 86 10 90 8-10 94 8

[0174] The polypeptide comprising SEQ ID NO: 126 thus shows extreme thermostability with significant antibacterial activity even at very high temperatures.

[0175] Similar results were obtained when using the same endolysin with another peptide or when using a variant of the endolysin (e.g. SEQ ID NO:7) with such peptides.

[0176] Particularly preferred embodiments of the invention are set forth once more in items 1 to 16 below: [0177] 1. Polypeptide comprising a first and a second amino acid sequence, wherein the first amino acid sequence is an endolysin, and wherein the second amino acid sequence is an antimicrobial peptide, cationic peptide, hydrophobic peptide, amphiphatic peptide or sushi peptide, and wherein the polypeptide comprises at least one sequence selected from the following group of sequences: [0178] i) an amino acid sequence according to SEQ ID NO: 1; [0179] ii) a derivative of SEQ ID NO: 1 exhibiting at least 80% sequence identity with SEQ ID NO:1, [0180] iii) an amino acid sequence according to SEQ ID NO:3; [0181] iv) a derivative of SEQ ID NO:3 exhibiting at least 77% sequence identity with SEQ ID NO:3; [0182] v) an amino acid sequence according to SEQ ID NO:4; and [0183] vi) a derivative of SEQ ID NO:4 exhibiting at least 80% sequence identity with SEQ ID NO:4. [0184] 2. The polypeptide according to item 1, wherein the first amino acid sequence is selected from the group consisting of: [0185] i) an amino acid sequence according to SEQ ID NO: 1; [0186] ii) a derivative of SEQ ID NO: 1 exhibiting at least 80% sequence identity with SEQ ID NO:1, [0187] iii) an amino acid sequence according to SEQ ID NO:2; and [0188] iv) a derivative of SEQ ID NO:2 exhibiting at least 80% sequence identity with SEQ ID NO:2, [0189] 3. The polypeptide according to item 2, wherein the derivative of SEQ ID NO:2 exhibits at least 85%, at least 87.5%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or more than 99% sequence identity with SEQ ID NO:2. [0190] 4. The polypeptide according to item 2 or item 3, wherein said derivative of SEQ ID NO:2 comprises a sequence according to SEQ ID NO:8, in particular wherein said derivative comprises a sequence according to SEQ ID NO: 13. [0191] 5. The polypeptide according any one of items 1 to 4, wherein the derivative of SEQ ID NO:1 exhibits at least 85%, at least 87.5%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or more than 99% sequence identity with SEQ ID NO: 1. [0192] 6. The polypeptide according to anyone of the preceding items, wherein the second amino acid sequence is selected from the group consisting of: [0193] i) an amino acid sequence according to SEQ ID NO:3; [0194] ii) a derivative of SEQ ID NO:3 exhibiting at least 77% sequence identity with SEQ ID NO:3; [0195] iii) an amino acid sequence according to SEQ ID NO:4; and [0196] iv) a derivative of SEQ ID NO:4 exhibiting at least 80% sequence identity with SEQ ID NO:4. [0197] 7. The polypeptide according to item 6, wherein the derivative of SEQ ID NO:3 exhibits at least 81%, at least 86%, at least 90%, or at least 95% sequence identity with SEQ ID NO:3, or wherein the derivative of SEQ ID NO:4 exhibits at least 83%, at least 86%, at least 90%, at least 93%, or at least 96% sequence identity with SEQ ID NO:4. [0198] 8. The polypeptide according to anyone of items 1 to 7, wherein the first amino acid sequence is SEQ ID NO: 1 or said derivative thereof, and wherein the second amino acid sequence is SEQ ID NO:3 or said derivative thereof, or wherein the first amino acid sequence is SEQ ID NO:2 or said derivative thereof, and wherein the second amino acid sequence is SEQ ID NO:4 or said derivative thereof. [0199] 9. The polypeptide according to anyone of items 1 to 8, wherein said derivative of SEQ ID NO:3 is a fragment of SEQ ID NO:3, in particular a fragment according to SEQ ID NO:37. [0200] 10. The polypeptide according to item 1, wherein [0201] i) the first amino acid sequence is SEQ ID NO: 1 and the second amino acid sequence is SEQ ID NO:3, or [0202] ii) wherein the first amino acid sequence is SEQ ID NO: 13 and the second amino acid sequence is SEQ ID NO:4. [0203] 11. The polypeptide according to item 13, wherein the polypeptide comprises an amino acid sequence according to SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 129 or SEQ ID NO: 130. [0204] 12. The polypeptide according to any one of items 1 to 11, wherein the polypeptide comprises an amino acid sequence as encoded by a nucleic acid sequence according to SEQ ID NO:153 or according to SEQ ID NO:154. [0205] 13. The polypeptide according to any one of the preceding items, wherein the polypeptide degrades the peptidoglycan of Salmonella bacteria. [0206] 14. Use of the polypeptide according to any one of items 1 to 13 as an antimicrobial in food, as an antimicrobial in feed, as an antimicrobial in cosmetics, or as disinfecting agent. [0207] 15. Method of controlling the growth of bacteria of the genus Salmonella in animals, in particular in livestock, companion animal and/or aquaculture, the method comprising contacting said animal, in particular the livestock, companion animal and/or aquaculture, with a polypeptide, wherein the polypeptide comprises a first and a second amino acid sequence, wherein the first amino acid sequence is an endolysin, and wherein the second amino acid sequence is an antimicrobial peptide, amphiphatic peptide, cationic peptide, hydrophobic peptide, sushi peptide or defensin, and wherein the polypeptide comprises at least one sequence selected from the following group of sequences: [0208] i) an amino acid sequence according to SEQ ID NO: 1; [0209] ii) a derivative of SEQ ID NO: 1 exhibiting at least 80% sequence identity with SEQ ID NO:1, [0210] iii) an amino acid sequence according to SEQ ID NO:2; [0211] iv) a derivative of SEQ ID NO:2 exhibiting at least 80% sequence identity with SEQ ID NO:2, [0212] v) an amino acid sequence according to SEQ ID NO:3; [0213] vi) a derivative of SEQ ID NO:3 exhibiting at least 77% sequence identity with SEQ ID NO:3; [0214] vii) an amino acid sequence according to SEQ ID NO:4; and [0215] viii) a derivative of SEQ ID NO:4 exhibiting at least 80% sequence identity with SEQ ID NO:4. [0216] 16. The method according to item 15, wherein the polypeptide is a polypeptide according to any one of items 1 to 13.