Antibiotic drugs targeting bacterial RNAs

Abstract

RNAs have diverse structures that include bulges and internal loops able to form tertiary contacts or serve as ligand binding sites. The recent increase in structural and functional information related to RNAs has put them in the limelight as a drug target for small molecule therapy. In addition, the recognition of the marked difference between prokaryotic and eukaryotic rRNA has led to the development of antibiotics that specifically target bacterial rRNA, reduce protein translation and thereby inhibit bacterial growth. To facilitate the development of new antibiotics targeting RNA, we here review the literature concerning such antibiotics, mRNA, riboswitch and tRNA and the key methodologies used for their screening.

Keywords: Antibiotics; Bacteria; Drug targeting; RNA.

Graphical abstract

Figure 1

The structures of antibiotic drugs (streptomycin, spectinomycin, tetracycline, and puromycin) whose mechanism of action is related to rRNA. A: Streptomycin, spectinomycin and tetracycline target bacterial 16S rRNA; puromycin resembles the 3′ end of the aminoacylated tRNA. B: Lincomycin, clindamycin, and chloramphenicol target bacterial 23S rRNA; mupirocin targets aminoacyl tRNA synthetase.

Figure 2

A: The secondary structures of partial 16S rRNA (numbers indicate nucleotide positions). Nucleotides interacting with spectinomycin, tetracycline and streptomycin are marked with red, green and yellow circles, respectively. B: The secondary structures of partial 23S rRNA. Nucleotides interacting with chloramphenicol, lincomycin and clindamycin, puromycin and tetracycline are marked with purple, green, yellow, and red circles, respectively.