The Serum Resistome of a Globally Disseminated Multidrug Resistant Uropathogenic <italic>Escherichia coli</italic> Clone

<title>Author Summary</title><p>The emergence and rapid dissemination of new bacterial pathogens presents multiple challenges to healthcare systems, including the need for rapid detection, precise diagnostics, effective transmission control and effective treatment. <italic>E. coli</italic> ST131 is an example of a recently emerged multidrug resistant pathogen that is capable of causing urinary tract and bloodstream infections with limited available treatment options. In order to increase our molecular understanding of <italic>E. coli</italic> ST131, we developed a high-throughput transposon mutagenesis system in combination with next generation sequencing to test every gene for its essential role in growth and for its contribution to serum resistance. We identified 315 essential genes, 270 of which were conserved among all currently available complete <italic>E. coli</italic> genomes. Fifty-six genes that define the serum resistome of <italic>E. coli</italic> ST131 were identified, including genes encoding membrane proteins, proteins involved in LPS biosynthesis, regulators and several novel proteins with previously unknown function. This study therefore provides an inventory of essential and serum resistance genes that could form a framework for the future development of targeted therapeutics to prevent disease caused by multidrug-resistant <italic>E. coli</italic> ST131 strains.</p>