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
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