Genomewide Identification of Essential Genes and Fitness Determinants of UA159

Transposon mutagenesis coupled with next-generation DNA sequencing (Tn-seq) is a powerful tool for discovering regions of the genome that are required for the survival of bacteria in different environments. We adapted this technique to the dental caries pathogen UA159 and identified 11% of the genome as essential, with many genes encoding products required for replication, translation, lipid metabolism, and cell wall biogenesis. Comparison of the essential genome of UA159 with those of selected other streptococci for which such information is available revealed several metabolic pathways and genes that are required in , but not in some spp. We further identified genes that are essential for sustained growth in rich or defined medium, as well as for persistence in a rodent model of oral infection. Collectively, our results provide a novel and comprehensive view of the genes required for essential processes of , many of which could represent potential targets for therapeutics. Tooth decay (dental caries) is a common cause of pain, impaired quality of life, and tooth loss in children and adults. It begins because of a compositional change in the microorganisms that colonize the tooth surface driven by repeated and sustained carbohydrate intake. Although several bacterial species are associated with tooth decay, is the most common cause. Therefore, it is important to identify biological processes that contribute to the survival of in the human mouth, with the aim of disrupting the processes with antimicrobial agents. We successfully applied Tn-seq to , discovering genes that are required for survival, growth, and persistence, both in laboratory environments and in a mouse model of tooth decay. This work highlights new avenues for the control of an important human pathogen.