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Antimicrobial Agents and Chemotherapy, May 2003, p. 1496-1502, Vol. 47, No. 5
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.5.1496-1502.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Role of 16S rRNA Helix 44 in Ribosomal Resistance to Hygromycin B

P. Pfister,1 M. Risch,1 D. E. Brodersen,2 and E. C. Böttger1*

Institut für Medizinische Mikrobiologie, Universität Zürich, CH-8028 Zürich, Switzerland,1 MRC Laboratory of Molecular Biology, Cambridge CB2 2QH, United Kingdom2

Received 22 November 2002/ Returned for modification 6 January 2003/ Accepted 3 February 2003

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.

* Corresponding author. Mailing address: Institut für Medizinische Mikrobiologie, Universität Zürich, Gloriastr. 30/32, CH-8028 Zürich, Switzerland. Phone: 41-1-634 26 60/61. Fax: 41-1-634 49 06. E-mail: boettger{at}immv.unizh.ch.

Antimicrobial Agents and Chemotherapy, May 2003, p. 1496-1502, Vol. 47, No. 5
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.5.1496-1502.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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