title: tRNA modification enzymes GidA and MnmE: potential role in virulence of bacterial pathogens.
abstract: Transfer RNA (tRNA) is an RNA molecule that carries amino acids to the ribosomes for protein synthesis. These tRNAs function at the peptidyl (P) and aminoacyl (A) binding sites of the ribosome during translation, with each codon being recognized by a specific tRNA. Due to this specificity, tRNA modification is essential for translational efficiency. Many enzymes have been implicated in the modification of bacterial tRNAs, and these enzymes may complex with one another or interact individually with the tRNA. Approximately, 100 tRNA modification enzymes have been identified with glucose-inhibited division (GidA) protein and MnmE being two of the enzymes studied. In Escherichia coli and Salmonella, GidA and MnmE bind together to form a functional complex responsible for the proper biosynthesis of 5-methylaminomethyl-2-thiouridine (mnm⁵s²U34) of tRNAs. Studies have implicated this pathway in a major pathogenic regulatory mechanism as deletion of gidA and/or mnmE has attenuated several bacterial pathogens like Salmonella enterica serovar Typhimurium, Pseudomonas syringae, Aeromonas hydrophila, and many others. In this review, we summarize the potential role of the GidA/MnmE tRNA modification pathway in bacterial virulence, interactions with the host, and potential therapeutic strategies resulting from a greater understanding of this regulatory mechanism.
authors.affiliation: Department of Animal Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA. dshippy@wisc.edu.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Shippy
authors.affiliation: Department of Animal Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA. fadl@wisc.edu.
authors.forename: Amin A
authors.initials: AA
authors.lastname: Fadl
mesh_terms: D000818:Animals; D001419:Bacteria / Q000472:pathogenicity*; D001424:Bacterial Infections / Q000378:metabolism* / Q000473:pathology; D018407:Bacterial Physiological Phenomena; D001426:Bacterial Proteins / Q000378:metabolism*; D004926:Escherichia coli / Q000472:pathogenicity / Q000502:physiology; D029968:Escherichia coli Proteins / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D012343:RNA, Transfer / Q000378:metabolism*; D014774:Virulence; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D037521:Virulence Factors; C108512:glucose-inhibited division protein A, bacteria; D012343:RNA, Transfer; D020558:GTP Phosphohydrolases; C492932:MnmE protein, E coli