Combined systems approaches reveal highly plastic responses to antimicrobial peptide challenge in Escherichia coli.
Obtaining an in-depth understanding of the arms races between peptides comprising the innate immune response and bacterial pathogens is of fundamental interest and will inform the development of new antibacterial therapeutics. We investigated whether a whole organism view of antimicrobial peptide (AMP) challenge on Escherichia coli would provide a suitably sophisticated bacterial perspective on AMP mechanism of action. Selecting structurally and physically related AMPs but with expected differences in bactericidal strategy, we monitored changes in bacterial metabolomes, morphological features and gene expression following AMP challenge at sub-lethal concentrations. For each technique, the vast majority of changes were specific to each AMP, with such a plastic response indicating E. coli is highly capable of discriminating between specific antibiotic challenges. Analysis of the ontological profiles generated from the transcriptomic analyses suggests this approach can accurately predict the antibacterial mode of action, providing a fresh, novel perspective for previous functional and biophysical studies.
King's College London, Institute of Pharmaceutical Science, London, United Kingdom.
Justyna
J
Kozlowska
King's College London, Institute of Pharmaceutical Science, London, United Kingdom.
Louic S
LS
Vermeer
King's College London, Institute of Pharmaceutical Science, London, United Kingdom.
Geraint B
GB
Rogers
King's College London, Institute of Pharmaceutical Science, London, United Kingdom.
Nabila
N
Rehnnuma
King's College London, Institute of Pharmaceutical Science, London, United Kingdom.
Sarah-Beth T A
SB
Amos
King's College London, King's College London Dental Institute at Guy's, King's and St. Thomas' Hospitals, London, United Kingdom.
Garrit
G
Koller
Department of Molecular Microbiology, John Innes Centre, Norwich, United Kingdom.
Michael
M
McArthur
King's College London, Institute of Pharmaceutical Science, London, United Kingdom.
Kenneth D
KD
Bruce
King's College London, Institute of Pharmaceutical Science, London, United Kingdom.
A James
AJ
Mason
D000220:Adaptation, Biological / Q000187:drug effects* / Q000235:genetics; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D055432:Metabolomics / Q000379:methods*; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D059467:Transcriptome / Q000187:drug effects
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides