Exact bacterial responses to antibiotics
Bacteria regulate gene expression in response to antibiotic stress. The EU-funded OPRA project has investigated if there is variability between cells as regards dynamic responses and if these are geared to increase survival. Very relevant to antibiotic design, they also looked at timing of antimicrobial dosage to maximise growth inhibition and death. Using Escherichia coli, the researchers measured the global gene regulatory response to the sudden addition of antibiotics tetracycline and chloramphenicol (translation inhibitors). Analysis of the data revealed that different genes respond at vastly different time scales ranging from minutes to hours. They identified a clear temporal hierarchy in which certain genes respond to the stress almost immediately, while others respond with a significant time delay. Interestingly, there were two dominant response modes – one resulting in permanent expression levels and the other a rapid, pulse-like increase and a quick return to the original level. Gene ontology enrichment analysis showed that many of the genes displaying the pulse-like behaviour were involved with response to acid stress response. Results therefore indicate that intracellular pH decreases as a result of antibiotics could act as a trigger for global stress responses. OPRA data stands to provide researchers with a picture of bacterial gene regulation and physiological changes in response to antibiotic stress. Furthermore, the results will enable prediction of optimised treatment strategies to avoid bacterial defence responses. Quantification of effective parameters that characterise gene regulation during antibiotic treatment has shed new light on how bacteria adapt to antibiotics. Researchers often assume that microbes respond to changes almost optimally. Project results challenge this and have provided a basic quantitative picture of the extent to which bacterial gene regulation in response to antibiotics is optimised.
Keywords
Bacterial, antibiotic, timing, antibiotic stress, OPRA
