Abstract 2092 Investigating recA regulation in DNA damage induced mutagenesis in A. baumannii

Acinetobacter baumannii is a gram-negative opportunistic pathogen part of an emerging group of transmittable hospital pathogens. Infections caused by A. baumannii are hard to treat due to the bacterium's resistance mechanisms consisting of mutagenesis and biofilm formation. A. baumannii acquires antibiotic resistance through a set of genes that are involved in DNA Damage Response (DDR). The DDR pathway contains gene products such as the error-prone DNA polymerases that are induced upon DNA damage. In A. baumannii, RecA, a recombinase protein, regulates the DDR pathway. However, the molecular mechanism associated with DNA-damage induced mutagenesis is not well understood in A. baumannii. To study this mechanism, cells containing a modified recA gene with a reporter green fluorescent protein (GFP) were utilized. Through treatment with UV radiation, mutations were induced in the cells and five distinct phenotypes with modified colony structure and altered GFP expression emerged as a result. An analysis of the genomes of the five phenotypes demonstrated that genes involved in metabolism and transcriptional regulation caused the phenotypic changes. Due to RecA's role in DNA repair in the DDR pathway, these genes may act as regulators of recA expression leading to mutant colony formation in A. baumannii upon DNA damage. Further investigation into the interactions of these genes with the DDR genes would provide insight into the cellular mechanism of the pathway. Through a detailed understanding of this pathway, targeted therapies can be developed to combat A. baumannii's multidrug resistance. The larger implication of this outcome includes lower incidence of hospital acquired infections through the development of effective therapies. This project was conducted partly in support from the Undergraduate Research and Fellowships Office at Northeastern University in Boston, Massachusetts.