Intracellular activity of the peptide antibiotic NZ2114: studies with Staphylococcus aureus and human THP-1 monocytes, and comparison with daptomycin and vancomycin

Karoline Sidelmann Brinch; Paul M Tulkens; Francoise Van Bambeke; Niels Frimodt-Møller; Niels Høiby; Hans-Henrik Kristensen

doi:10.1093/jac/dkq159

Intracellular activity of the peptide antibiotic NZ2114: studies with Staphylococcus aureus and human THP-1 monocytes, and comparison with daptomycin and vancomycin

Karoline Sidelmann Brinch, Paul M Tulkens, Francoise Van Bambeke, Niels Frimodt-Møller, Niels Høiby, Hans-Henrik Kristensen

Department of Immunology and Microbiology

31 Citations (Scopus)

Abstract

Objectives: Staphylococcus aureus survives inside eukaryotic cells. Our objective was to assess the activity of NZ2114, a novel peptidic antibiotic, against intracellular S. aureus in comparison with established antistaphylococcal agents acting on the bacterial envelope with a distinct mechanism. Methods: The extracellular (broth) and intracellular (THP-1 monocytes) activities of NZ2114 were compared with those of vancomycin and daptomycin against methicillin-susceptible S. aureus (MSSA), methicillin-resistant S. aureus (MRSA) and vancomycin-resistant S. aureus (VRSA). Results: All three compounds showed an extracellular bactericidal effect (>3 log₁₀ kill) against MSSA and MRSA. Daptomycin and NZ2114 also exhibited bactericidal activity against VRSA. The extracellular killing was concentration dependent for all three compounds within the range of drug concentrations tested. The intracellular experiments demonstrated a maximal intracellular effect of NZ2114 after 24 h as a 5 log₁₀ cfu reduction against MSSA (ATCC 25923), while the activity was a 0.9 log₁₀ cfu reduction against MRSA and a 0.2 log₁₀ cfu reduction against VRSA. For comparison, the intracellular activity of daptomycin was a 1.0 log₁₀ cfu reduction against MSSA, a 0.8 log₁₀ cfu reduction against MRSA and a 0.3 log₁₀ cfu reduction against VRSA. Vancomycin showed activity against both MSSA and MRSA (0.6 log₁₀ cfu reduction), whereas VRSA was resistant to vancomycin. Conclusions: NZ2114 displayed similar extracellular and intracellular activities as daptomycin, and was more effective than vancomycin against the intracellular forms of susceptible bacteria. However, the study also showed that the intracellular activities of NZ2114 and daptomycin are weaker than their extracellular activities.

Original language	English
Journal	Journal of Antimicrobial Chemotherapy
Volume	65
Issue number	8
Pages (from-to)	1720-4
Number of pages	5
ISSN	0305-7453
DOIs	https://doi.org/10.1093/jac/dkq159 https://doi.org/10.1093/jac/dkq159
Publication status	Published - 9 Jun 2010

Keywords

Anti-Bacterial Agents
Cell Line
Colony Count, Microbial
Daptomycin
Humans
Microbial Sensitivity Tests
Microbial Viability
Monocytes
Peptides
Staphylococcus aureus
Vancomycin

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Brinch, K. S., Tulkens, P. M., Van Bambeke, F., Frimodt-Møller, N., Høiby, N., & Kristensen, H-H. (2010). Intracellular activity of the peptide antibiotic NZ2114: studies with Staphylococcus aureus and human THP-1 monocytes, and comparison with daptomycin and vancomycin. Journal of Antimicrobial Chemotherapy, 65(8), 1720-4. https://doi.org/10.1093/jac/dkq159, https://doi.org/10.1093/jac/dkq159

Intracellular activity of the peptide antibiotic NZ2114: studies with Staphylococcus aureus and human THP-1 monocytes, and comparison with daptomycin and vancomycin. / Brinch, Karoline Sidelmann; Tulkens, Paul M; Van Bambeke, Francoise et al.

In: Journal of Antimicrobial Chemotherapy, Vol. 65, No. 8, 09.06.2010, p. 1720-4.

Research output: Contribution to journal › Journal article › Research › peer-review

Brinch, KS, Tulkens, PM, Van Bambeke, F, Frimodt-Møller, N, Høiby, N & Kristensen, H-H 2010, 'Intracellular activity of the peptide antibiotic NZ2114: studies with Staphylococcus aureus and human THP-1 monocytes, and comparison with daptomycin and vancomycin', Journal of Antimicrobial Chemotherapy, vol. 65, no. 8, pp. 1720-4. https://doi.org/10.1093/jac/dkq159, https://doi.org/10.1093/jac/dkq159

Brinch KS, Tulkens PM, Van Bambeke F, Frimodt-Møller N, Høiby N, Kristensen H-H. Intracellular activity of the peptide antibiotic NZ2114: studies with Staphylococcus aureus and human THP-1 monocytes, and comparison with daptomycin and vancomycin. Journal of Antimicrobial Chemotherapy. 2010 Jun 9;65(8):1720-4. doi: 10.1093/jac/dkq159, http://dx.doi.org/10.1093/jac/dkq159

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title = "Intracellular activity of the peptide antibiotic NZ2114: studies with Staphylococcus aureus and human THP-1 monocytes, and comparison with daptomycin and vancomycin",

abstract = "Objectives: Staphylococcus aureus survives inside eukaryotic cells. Our objective was to assess the activity of NZ2114, a novel peptidic antibiotic, against intracellular S. aureus in comparison with established antistaphylococcal agents acting on the bacterial envelope with a distinct mechanism. Methods: The extracellular (broth) and intracellular (THP-1 monocytes) activities of NZ2114 were compared with those of vancomycin and daptomycin against methicillin-susceptible S. aureus (MSSA), methicillin-resistant S. aureus (MRSA) and vancomycin-resistant S. aureus (VRSA). Results: All three compounds showed an extracellular bactericidal effect (>3 log10 kill) against MSSA and MRSA. Daptomycin and NZ2114 also exhibited bactericidal activity against VRSA. The extracellular killing was concentration dependent for all three compounds within the range of drug concentrations tested. The intracellular experiments demonstrated a maximal intracellular effect of NZ2114 after 24 h as a 5 log10 cfu reduction against MSSA (ATCC 25923), while the activity was a 0.9 log10 cfu reduction against MRSA and a 0.2 log10 cfu reduction against VRSA. For comparison, the intracellular activity of daptomycin was a 1.0 log10 cfu reduction against MSSA, a 0.8 log10 cfu reduction against MRSA and a 0.3 log10 cfu reduction against VRSA. Vancomycin showed activity against both MSSA and MRSA (0.6 log10 cfu reduction), whereas VRSA was resistant to vancomycin. Conclusions: NZ2114 displayed similar extracellular and intracellular activities as daptomycin, and was more effective than vancomycin against the intracellular forms of susceptible bacteria. However, the study also showed that the intracellular activities of NZ2114 and daptomycin are weaker than their extracellular activities.",

keywords = "Anti-Bacterial Agents, Cell Line, Colony Count, Microbial, Daptomycin, Humans, Microbial Sensitivity Tests, Microbial Viability, Monocytes, Peptides, Staphylococcus aureus, Vancomycin",

author = "Brinch, {Karoline Sidelmann} and Tulkens, {Paul M} and {Van Bambeke}, Francoise and Niels Frimodt-M{\o}ller and Niels H{\o}iby and Hans-Henrik Kristensen",

year = "2010",

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doi = "10.1093/jac/dkq159",

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journal = "Journal of Antimicrobial Chemotherapy",

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T1 - Intracellular activity of the peptide antibiotic NZ2114: studies with Staphylococcus aureus and human THP-1 monocytes, and comparison with daptomycin and vancomycin

AU - Brinch, Karoline Sidelmann

AU - Tulkens, Paul M

AU - Van Bambeke, Francoise

AU - Frimodt-Møller, Niels

AU - Høiby, Niels

AU - Kristensen, Hans-Henrik

PY - 2010/6/9

Y1 - 2010/6/9

N2 - Objectives: Staphylococcus aureus survives inside eukaryotic cells. Our objective was to assess the activity of NZ2114, a novel peptidic antibiotic, against intracellular S. aureus in comparison with established antistaphylococcal agents acting on the bacterial envelope with a distinct mechanism. Methods: The extracellular (broth) and intracellular (THP-1 monocytes) activities of NZ2114 were compared with those of vancomycin and daptomycin against methicillin-susceptible S. aureus (MSSA), methicillin-resistant S. aureus (MRSA) and vancomycin-resistant S. aureus (VRSA). Results: All three compounds showed an extracellular bactericidal effect (>3 log10 kill) against MSSA and MRSA. Daptomycin and NZ2114 also exhibited bactericidal activity against VRSA. The extracellular killing was concentration dependent for all three compounds within the range of drug concentrations tested. The intracellular experiments demonstrated a maximal intracellular effect of NZ2114 after 24 h as a 5 log10 cfu reduction against MSSA (ATCC 25923), while the activity was a 0.9 log10 cfu reduction against MRSA and a 0.2 log10 cfu reduction against VRSA. For comparison, the intracellular activity of daptomycin was a 1.0 log10 cfu reduction against MSSA, a 0.8 log10 cfu reduction against MRSA and a 0.3 log10 cfu reduction against VRSA. Vancomycin showed activity against both MSSA and MRSA (0.6 log10 cfu reduction), whereas VRSA was resistant to vancomycin. Conclusions: NZ2114 displayed similar extracellular and intracellular activities as daptomycin, and was more effective than vancomycin against the intracellular forms of susceptible bacteria. However, the study also showed that the intracellular activities of NZ2114 and daptomycin are weaker than their extracellular activities.

AB - Objectives: Staphylococcus aureus survives inside eukaryotic cells. Our objective was to assess the activity of NZ2114, a novel peptidic antibiotic, against intracellular S. aureus in comparison with established antistaphylococcal agents acting on the bacterial envelope with a distinct mechanism. Methods: The extracellular (broth) and intracellular (THP-1 monocytes) activities of NZ2114 were compared with those of vancomycin and daptomycin against methicillin-susceptible S. aureus (MSSA), methicillin-resistant S. aureus (MRSA) and vancomycin-resistant S. aureus (VRSA). Results: All three compounds showed an extracellular bactericidal effect (>3 log10 kill) against MSSA and MRSA. Daptomycin and NZ2114 also exhibited bactericidal activity against VRSA. The extracellular killing was concentration dependent for all three compounds within the range of drug concentrations tested. The intracellular experiments demonstrated a maximal intracellular effect of NZ2114 after 24 h as a 5 log10 cfu reduction against MSSA (ATCC 25923), while the activity was a 0.9 log10 cfu reduction against MRSA and a 0.2 log10 cfu reduction against VRSA. For comparison, the intracellular activity of daptomycin was a 1.0 log10 cfu reduction against MSSA, a 0.8 log10 cfu reduction against MRSA and a 0.3 log10 cfu reduction against VRSA. Vancomycin showed activity against both MSSA and MRSA (0.6 log10 cfu reduction), whereas VRSA was resistant to vancomycin. Conclusions: NZ2114 displayed similar extracellular and intracellular activities as daptomycin, and was more effective than vancomycin against the intracellular forms of susceptible bacteria. However, the study also showed that the intracellular activities of NZ2114 and daptomycin are weaker than their extracellular activities.

KW - Anti-Bacterial Agents

KW - Cell Line

KW - Colony Count, Microbial

KW - Daptomycin

KW - Humans

KW - Microbial Sensitivity Tests

KW - Microbial Viability

KW - Monocytes

KW - Peptides

KW - Staphylococcus aureus

KW - Vancomycin

U2 - 10.1093/jac/dkq159

DO - 10.1093/jac/dkq159

M3 - Journal article

C2 - 20534628

SN - 0305-7453

VL - 65

SP - 1720

EP - 1724

JO - Journal of Antimicrobial Chemotherapy

JF - Journal of Antimicrobial Chemotherapy

IS - 8

ER -

Intracellular activity of the peptide antibiotic NZ2114: studies with Staphylococcus aureus and human THP-1 monocytes, and comparison with daptomycin and vancomycin

Abstract

Keywords

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