Role of 16S rRNA Helix 44 in Ribosomal Resistance to Hygromycin B.
Hygromycin B is an aminoglycoside antibiotic active against prokaryotic and eukaryotic ribosomes. Ribosomal alterations in bacteria conferring resistance to hygromycin B have not been described, prompting us to use a single rRNA allelic derivative of the gram-positive bacterium Mycobacterium smegmatis for investigation of the molecular mechanisms involved in ribosomal resistance to hygromycin B in eubacteria. Resistance mutations were found to localize exclusively in 16S rRNA. The mutations observed, i.e., 16S rRNA U1406C, C1496U, and U1498C (E. coli numbering), are in close proximity to the hygromycin B binding site located in conserved helix 44 of 16S rRNA. The 16S rRNA positions involved in hygromycin B resistance are highly conserved in all three domains of life, explaining the lack of specificity and general toxicity of hygromycin B.
Pfister
P
P
Institut für Medizinische Mikrobiologie, Universität Zürich, CH-8028 Zürich, Switzerland.
Risch
M
M
Brodersen
D E
DE
Böttger
E C
EC
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D006921:Hygromycin B / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D020102:Mycobacterium smegmatis / Q000187:drug effects* / Q000235:genetics; D017354:Point Mutation; D012329:RNA, Bacterial / Q000737:chemistry*; D012336:RNA, Ribosomal, 16S / Q000737:chemistry*; D012270:Ribosomes / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D012329:RNA, Bacterial; D012336:RNA, Ribosomal, 16S; D006921:Hygromycin B