Combined systems approaches reveal highly plastic responses to antimicrobial peptide challenge in escherichia coli
Autor: | Nabila Rehnnuma, Garrit Koller, Michael McArthur, Louic S. Vermeer, Sarah-Beth T. A. Amos, A. James Mason, Kenneth D. Bruce, Geraint B. Rogers, Justyna Kozlowska |
---|---|
Jazyk: | angličtina |
Rok vydání: | 2014 |
Předmět: |
Adaptation
Biological Pathogenesis Pathology and Laboratory Medicine medicine.disease_cause Biochemistry Medicine and Health Sciences Gram Negative lcsh:QH301-705.5 Peptide sequence Immune System Proteins Systems Biology Antimicrobial Bacterial Pathogens Anti-Bacterial Agents Medical Microbiology Host-Pathogen Interactions Metabolic Pathways Whole Organism Research Article lcsh:Immunologic diseases. Allergy RM Molecular Sequence Data Immunology Microbial Sensitivity Tests Biology Microbiology Metabolomics Microscopy Electron Transmission Virology Defense Proteins Escherichia coli Genetics medicine Pleurocidin Amino Acid Sequence Mode of action Microbial Pathogens Nuclear Magnetic Resonance Biomolecular Molecular Biology Innate immune system Dose-Response Relationship Drug Biology and Life Sciences Proteins Bacteriology Gene Expression Regulation Bacterial QR Metabolism lcsh:Biology (General) Microscopy Electron Scanning Parasitology Transcriptome lcsh:RC581-607 Antimicrobial Cationic Peptides |
Zdroj: | PLoS Pathogens, Vol 10, Iss 5, p e1004104 (2014) PLoS Pathogens |
ISSN: | 1553-7374 |
Popis: | 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. Author Summary Antimicrobial peptides (AMP) are small proteins with often potent antibacterial activity found in a variety of organisms, including humans. Understanding how these antibiotics operate is challenging and often controversial since many studies have necessarily focussed on identifying a single major cause of bacterial cell death while, increasingly, others have cautioned that AMPs are likely to have access to multiple bactericidal features. Systems biology is an emerging field that comprises a series of techniques capable of giving a global view of how bacteria respond to external stimuli. Here we have monitored changes in gene expression and metabolism in bacteria that have been challenged with sub-lethal concentrations of four different AMPs. By understanding how bacteria respond to a threat we can reveal how the bacteria perceive the AMP to be operating. Our approach provides a sophisticated bacterial perspective of the mode of action of each AMP and reveals that the bacteria have a vast array of weapons that can be marshalled to deal with distinct AMP threats. Indeed, around a third (or even more) of the bacterial machinery might be useful in dealing with antibiotic challenges, highlighting why antibiotic resistance is such a persistent problem. |
Databáze: | OpenAIRE |
Externí odkaz: |