Strain Dependent Genetic Networks for Antibiotic-Sensitivity in a Bacterial Pathogen with a Large Pan-Genome

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<title>Author Summary</title> <p>While antibiotic resistant bacterial pathogens cause millions of deaths each year it remains largely unclear how a bacterium deals with antibiotic-induced stress and how this leads to the emergence of resistance. Moreover, many bacterial species are composed of strains whose genomes vary considerably, and while this variation may significantly affect phenotypes such as antibiotic sensitivity, its importance is unknown. Here we apply the method Tn-Seq, showing it is feasible to develop a detailed view of how a bacterium experiences antibiotic stress, while simultaneously determining the influence of the genomic-background. We show for two strains of the bacterial pathogen <italic>Streptococcus pneumoniae</italic> that, even though they experience the same stress triggered by daptomycin, they use a majority of different genes to withstand this stress, including genes important for integrity of the membrane, potassium uptake and protein turnover. Additionally, by untangling underlying genomic networks we unexpectedly expose large differences in genetic-interactions as well as transcriptional regulation. Our study provides not only a sensitive approach to untangle the influence of the genomic-background on phenotypes such as antibiotic sensitivity, but also highlights that this knowledge is instrumental in understanding how bacteria respond to environmental stress, which in turn influences the manner in which they evolve.</p>




van Opijnen, T., Dedrick, S., & Bento, J. (2016). Strain Dependent Genetic Networks for Antibiotic-Sensitivity in a Bacterial Pathogen with a Large Pan-Genome. PLoS Pathogens, 12(9).

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