Poster abstracts

Poster number 54 submitted by Theresa Rogers

A pseudo-tRNA modulates antibiotic resistance in Bacillus cereus

Theresa E. Rogers (Department of Microbiology, The Ohio State University), Sandro Ataide (Department of Microbiology, The Ohio State University), Michael Ibba (Department of Microbiology, The Ohio State University)

Abstract:
Transfer RNAs (tRNAs) are primarily responsible for translation of the genetic code and function in numerous other processes such as viral replication, amino acid biosynthesis, and cell wall remodeling. tRNAs have also been shown to regulate gene expression by acting as sensors of the translation status of the cell, and it has been suggested that these highly stable molecules could provide a structural framework for small RNAs (sRNAs) that regulate other cellular processes. A pseudo-tRNA from Bacillus cereus, tRNA^Other, does not associate with polysomes, suggesting a role outside translation. Deletion of tRNA^Other leads to changes in cell wall morphology and significantly reduces resistance against a number of unrelated antibiotics including vancomycin, puromycin, novobiocin, and rifapentin. The deletion of tRNA^Other is also accompanied by significant changes in the expression of numerous genes involved in oxidative stress response, several of which contain significant sequence complementarities to tRNA^Other, suggesting a possible regulatory sRNA function. Recent studies have shown that many bactericidal antibiotics act in part by inducing intracellular oxidative stress (1). Additional studies have shown that NO produced by bacterial nitric oxide synthase (NOS) can act as an antioxidant, thereby reducing oxidative stress (2). Deletion of tRNA^Other significantly reduces nos transcript levels and intracellular NO production. Expression of tRNA^Other changes in response to extracellular iron concentration, consistent with the presence of three putative ferric uptake regulator (Fur) bindings sites in the predicted promoter region of the corresponding gene. Unbound intracellular iron is involved in oxidative stress, in that ferrous iron can generate hydroxyl radicals through the Fenton reaction. Taken together, these findings indicate that tRNA^Other is an iron-responsive sRNA that modulates antibiotic resistance by regulating the expression of multiple targets involved in oxidative stress response.

References:
1. Kohanski, M.A., et al. A common mechanism of cellular death induced by bactericidal antibiotics. 2007. Cell. 130:797-810.

2. Gusarov, I., et al. Endogenous nitric oxide protects bacteria against a wide spectrum of antibiotics. 2009. Science. 325:1380-1384.

Keywords: pseudo-tRNA, sRNA, antibiotic resistance