TY - JOUR
T1 - In silico identification of two peptides with antibacterial activity against multidrug-resistant Staphylococcus aureus
AU - Oyama, Linda B.
AU - Olleik, Hamza
AU - Teixeira, Ana Carolina Nery
AU - Guidini, Matheus M.
AU - Pickup, James A.
AU - Hui, Brandon Yeo Pei
AU - Vidal, Nicolas
AU - Cookson, Alan R.
AU - Vallin, Hannah
AU - Wilkinson, Toby
AU - Bazzolli, Denise M. S.
AU - Richards, Jennifer
AU - Wootton, Mandy
AU - Mikut, Ralf
AU - Hilpert, Kai
AU - Maresca, Marc
AU - Perrier, Josette
AU - Hess, Matthias
AU - Mantovani, Hilario C.
AU - Fernandez-Fuentes, Narcis
AU - Creevey, Christopher J.
AU - Huws, Sharon A.
PY - 2022/7/14
Y1 - 2022/7/14
N2 - Here we report two antimicrobial peptides (AMPs), HG2 and HG4 identified from a rumen microbiome metagenomic dataset, with activity against multidrug-resistant (MDR) bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA) strains, a major hospital and community-acquired pathogen. We employed the classifier model design to analyse, visualise, and interpret AMP activities. This approach allowed in silico discrimination of promising lead AMP candidates for experimental evaluation. The lead AMPs, HG2 and HG4, are fast-acting and show anti-biofilm and anti-inflammatory activities in vitro and demonstrated little toxicity to human primary cell lines. The peptides were effective in vivo within a Galleria mellonella model of MRSA USA300 infection. In terms of mechanism of action, HG2 and HG4 appear to interact with the cytoplasmic membrane of target cells and may inhibit other cellular processes, whilst preferentially binding to bacterial lipids over human cell lipids. Therefore, these AMPs may offer additional therapeutic templates for MDR bacterial infections.
AB - Here we report two antimicrobial peptides (AMPs), HG2 and HG4 identified from a rumen microbiome metagenomic dataset, with activity against multidrug-resistant (MDR) bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA) strains, a major hospital and community-acquired pathogen. We employed the classifier model design to analyse, visualise, and interpret AMP activities. This approach allowed in silico discrimination of promising lead AMP candidates for experimental evaluation. The lead AMPs, HG2 and HG4, are fast-acting and show anti-biofilm and anti-inflammatory activities in vitro and demonstrated little toxicity to human primary cell lines. The peptides were effective in vivo within a Galleria mellonella model of MRSA USA300 infection. In terms of mechanism of action, HG2 and HG4 appear to interact with the cytoplasmic membrane of target cells and may inhibit other cellular processes, whilst preferentially binding to bacterial lipids over human cell lipids. Therefore, these AMPs may offer additional therapeutic templates for MDR bacterial infections.
KW - Animals
KW - Humans
KW - Staphylococcus aureus
KW - Staphylococcal Infections
KW - Lipids
KW - Antimicrobial Cationic Peptides
KW - Adenosine Monophosphate
KW - Anti-Bacterial Agents
KW - Microbial Sensitivity Tests
KW - Methicillin-Resistant Staphylococcus aureus
U2 - 10.1038/s41522-022-00320-0
DO - 10.1038/s41522-022-00320-0
M3 - Article
C2 - 35835775
SN - 2055-5008
VL - 8
JO - NPJ Biofilms and Microbiomes
JF - NPJ Biofilms and Microbiomes
M1 - 58
ER -