Bacterial persistence, which is a phenomenon where subpopulations of isogenic bacteria are killed more slowly during antibiotic treatment than the majority of the population, is implicated in recurring infections and the development of antibiotic resistance. Persisters have been observed in populations of many bacterial species, including Pseudomonas aeruginosa, which is a common cause of hospital-acquired infections and lung infections in cystic fibrosis patients. P. aeruginosa infections can be treated with fluoroquinolone (FQ) antibiotics, which can kill growing and nongrowing bacteria by causing DNA damage. Previous studies have found that repair of DNA damage is important for FQ persistence in the model organism Escherichia coli. However, P. aeruginosa exhibits differences in its DNA damage repair machinery compared to E. coli, such as containing the machinery to perform non-homologous end joining (NHEJ) for repair of DNA double-stranded breaks (DSBs). 

In this dissertation, we used a genetic approach to explore if DNA damage repair is important for FQ persistence of P. aeruginosa. First, we found that loss of homologous recombination (a DSB repair system) and the SOS response reduced FQ persister levels of P. aeruginosa and E. coli in stationary-phase cultures. Alternatively, these systems were not important for persistence of exponentially growing P. aeruginosa cultures, which differed from E. coli in the same conditions. Next, we found that loss of NHEJ did not impact FQ persister levels, and overexpression of NHEJ machinery in P. aeruginosa had toxic effects. Lastly, we examined the roles of single-stranded DNA repair systems in FQ persistence of P. aeruginosa and found that UvrD is important for persistence of stationary-phase but not exponential-phase populations. 

Collectively, we identified several DNA repair systems important for persistence of stationary-phase P. aeruginosa populations; however, none of the repair machinery that we tested impacted exponential-phase persister levels. Whether exponential-phase P. aeruginosa FQ persisters experience DNA damage and, if so, how they repair that damage represent areas for future work. Furthermore, we showed that the roles of DNA repair in FQ persister survival in E. coli are not necessarily the same as P. aeruginosa, highlighting the importance of directly studying persistence in pathogens of interest