E-MTAB-1703 - Transcription profiling by array of E. coli cells challenged with four different antimicrobial peptides to investigate transcriptomic responses to antimicrobial peptide challenge
Released on 21 January 2014, last updated on 2 May 2014
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. Many cationic antimicrobial peptides (AMPs) share a range of structural and physical features that have been linked to antibacterial activity and yet they vary dramatically in their potency towards the same bacterial target. We hypothesised that a whole organism view of AMP challenge on Escherichia coli could provide a sophisticated, bacterial perspective enabling understanding of how potency is linked to mode of action. We used a 1H NMR metabolomic approach to characterise the effect on E. coli of challenge with four structurally and physically related AMPs: magainin 2, pleurocidin, buforin II and a designed peptide comprising D-amino acids only. Sub-inhibitory conditions, where these peptides nevertheless induced a bacterial response, were identified enabling electron microscopic and transcriptomic analyses. Although some common features of the bacterial response to AMP challenge could be identified, the metabolomes, morphological changes and the vast majority of the changes in gene expression were specific to each AMP. We show the antibacterial mode of action of AMPs can be accurately predicted by comparing ontological profiles generated by transcriptomic analyses. The response of E. coli to AMP challenge is highly plastic, with the bacteria capable of deploying a multifaceted response adapted to the mode of action rather than the physical properties of the AMP.
transcription profiling by array, all pairs, co-expression, compound treatment
An integrated systems biology approach reveals highly plastic responses to antimicrobial peptide challenge in Escherichia coli. Justyna Kozlowska, Louic S. Vermeer, Geraint B. Rogers, Nabila Rehnnuma, Garrit Koller, Michael McArthur, Kenneth D. Bruce, A. James Mason.