Determining Mechanism Used By Bacteria To Evade Bactericidal Conditions, By The Way Of Resistance And Persistence

Abstract

The three main chapters of this thesis (Ch2,Ch3,Ch4) address the topics of antibiotic resistance, persistence and thymineless death respectively. The antibiotic resistance chapter (Ch2) focused on determining mutation hierarchy and predicting mutational paths different species of bacteria take to reach clinical levels of fluoroquinolone resistance. Based on the findings described in the chapter, many bacterial species appear to have a distinct mutational pattern, that can be used to predict future development of fluoroquinolone resistance.The persistence-focused chapter (Ch3) links the clinically relevant antibiotic resistance mutations to the high-persistence phenotype, while identifying some of the underlying molecular mechanisms used by bacteria to induce persister state. Finally, the thymineless death chapter (Ch4) focuses on identifying the mechanism of killing bacteria via thymine limitation. In this chapter we show that premature deposition of ftsZ rings triggered by prolonged thymine starvation plays a crucial role in determining bacterial survival. Altogether, this thesis work attempts to gain insights into strategies bacteria have at their disposal to evade antibiotic-mediated death, while at the same time attempting to offer real world solutions. It is my hope that this body of work, in combination with others’ research, will someday usher changes that ultimately will help to reign in the rampant spread of antibiotic resistance.