TY - JOUR
T1 - Efficacy of newly generated short antimicrobial cationic lipopeptides against methicillin-resistant Staphylococcus aureus (MRSA)
AU - Greber, Katarzyna E.
AU - Roch, Melanie
AU - Rosato, Mauro A.
AU - Martinez, Maria P.
AU - Rosato, Adriana E.
N1 - Funding Information:
We acknowledge Dr James Gu, Director of the Electron Microscopy Core, for his technical assistance with the Scanning Electron Microscopy experiments. The mass spectrometry service was provided by the Laboratory of Mass Spectrometry at the Intercollegiate Faculty of Biotechnology University of Gdansk and Medical University of Gdansk. We would like to acknowledge the Mobi4Health EU project that allowed us to use high-quality mass spectrometers. Funding: No funding was associated with this study. Competing Interests: None. Ethical Approval: Not required.
Publisher Copyright:
© 2019 Elsevier B.V. and International Society of Chemotherapy
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/3
Y1 - 2020/3
N2 - Introduction: Infection caused by methicillin-resistant Staphylococcus aureus (S. aureus) (MRSA) is a serious clinical challenge and research to develop new antimicrobials is imperative. Methods: This study investigated the in vitro and in vivo efficacy of the short cationic dialkyl lipopeptides (C10)2-KKKK-NH2 and (C12)2-KKKK-NH2. The antibacterial efficacy of (C10)2-KKKK-NH2 and (C12)2-KKKK-NH2 was evaluated in representative clinical methicillin-susceptible S. aureus and MRSA strains by both in vitro (MIC, time-kill curve) and in vivo (wax worms model) approaches. Results: These studies revealed that both (C10)2-KKKK-NH2 and (C12)2-KKKK-NH2 have rapid bactericidal activity, with a decrease of > 3 log10 colony forming units (CFU)/mL achieved in the first 6 hours of treatment. Furthermore, (C10)2-KKKK-NH2 performed similarly to daptomycin, with a sustained bacterial killing after 24 hours. Wax worms infected and treated with these lipopeptides showed a decreased survival rate of 90% to 50% within the first day of treatment. Scanning electron microscopy determined that the effect of the short lipopeptides in S. aureus was associated with important morphological structural changes that may suggest cell membrane perturbation. Conclusion: These findings suggest that the short lipopeptides (C10)2-KKKK-NH2 and (C12)2-KKKK-NH2 may be potential new options for treating MRSA infections.
AB - Introduction: Infection caused by methicillin-resistant Staphylococcus aureus (S. aureus) (MRSA) is a serious clinical challenge and research to develop new antimicrobials is imperative. Methods: This study investigated the in vitro and in vivo efficacy of the short cationic dialkyl lipopeptides (C10)2-KKKK-NH2 and (C12)2-KKKK-NH2. The antibacterial efficacy of (C10)2-KKKK-NH2 and (C12)2-KKKK-NH2 was evaluated in representative clinical methicillin-susceptible S. aureus and MRSA strains by both in vitro (MIC, time-kill curve) and in vivo (wax worms model) approaches. Results: These studies revealed that both (C10)2-KKKK-NH2 and (C12)2-KKKK-NH2 have rapid bactericidal activity, with a decrease of > 3 log10 colony forming units (CFU)/mL achieved in the first 6 hours of treatment. Furthermore, (C10)2-KKKK-NH2 performed similarly to daptomycin, with a sustained bacterial killing after 24 hours. Wax worms infected and treated with these lipopeptides showed a decreased survival rate of 90% to 50% within the first day of treatment. Scanning electron microscopy determined that the effect of the short lipopeptides in S. aureus was associated with important morphological structural changes that may suggest cell membrane perturbation. Conclusion: These findings suggest that the short lipopeptides (C10)2-KKKK-NH2 and (C12)2-KKKK-NH2 may be potential new options for treating MRSA infections.
KW - Antimicrobial lipopeptides
KW - Galleria mellonella
KW - In vivo infection model
KW - Methicillin-resistant Staphylococcus aureus (MRSA)
KW - Staphylococcus aureus
KW - Wax worms
KW - Anti-Bacterial Agents/chemistry
KW - Animals
KW - Daptomycin/pharmacology
KW - Methicillin-Resistant Staphylococcus aureus/drug effects
KW - Lipopeptides/chemistry
KW - Staphylococcal Infections/drug therapy
UR - http://www.scopus.com/inward/record.url?scp=85079534378&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85079534378&partnerID=8YFLogxK
U2 - 10.1016/j.ijantimicag.2019.10.008
DO - 10.1016/j.ijantimicag.2019.10.008
M3 - Article
C2 - 31634552
AN - SCOPUS:85079534378
SN - 0924-8579
VL - 55
SP - 105827
JO - International Journal of Antimicrobial Agents
JF - International Journal of Antimicrobial Agents
IS - 3
M1 - 105827
ER -