TY - JOUR
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 -