Investigating the Basis of Phenotypic Variation in the DNA Damage Response of Acinetobacter baumannii

Abstract

Classified as an “ESKAPE” pathogen, Acinetobacter baumannii is one of the leading causes of hospital‐acquired (nosocomial) infections. This Gram‐negative opportunistic pathogen is able to survive desiccation and rapidly acquire multi‐drug resistances. The bacterium's successful mutagenic and antibiotic resistant capabilities are linked to its unique regulation of the DNA Damage Response (DDR). In similarity to many other bacteria, the DDR in A. baumannii depends on RecA, a highly conserved recombinase. However, in A. baumannii, the DDR is bimodal and promotes phenotypic variation; meaning that a fraction of cells—with the same genetic information— respond very well to DNA damage while others do not. It is predicted that this bimodal gene expression is a bet‐hedging strategy that contributes to the persistent survivability of A. baumannii by providing a mechanism for acquisition of advantageous mutations, such as those for antibiotic resistance.We have shown that the recA gene transcript contains an extended structured 5′UTR that influences bimodal gene expression. One of the 5′UTR elements, an outer loop, possesses an influential role as a cis‐regulatory element. We have shown that RNA binding proteins (RBPs) bind specifically to the native UTR when DNA damage is induced. We have identified one of these proteins as a chaperonin known for its ability to bind to RNA and stabilize structure. We aim to further investigate these proteins and their sequence specific binding as we hypothesize that the outer loop is a binding site for RBPs, which would loosen and open the UTR to promote translation of the recA transcript. These findings provide insight to recA regulation, which in turn affects the DDR in A. baumannii. Understanding the DDR will permit to devise novel strategies to eliminate A. baumannii from clinical wards.Support or Funding InformationThis work is supported by grants from Northeastern University's Office of Undergraduate Research and Fellowships and Northeastern University's Honors Department.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.