SINGLE 16S RIBOSOMAL-RNA SUBSTITUTION IS RESPONSIBLE FOR RESISTANCE TO AMIKACIN AND OTHER 2-DEOXYSTREPTAMINE AMINOGLYCOSIDES IN MYCOBACTERIUM-ABSCESSUS AND MYCOBACTERIUM-CHELONAE

Twenty-six clinical isolates of Mycobacterium abscessus resistant to a mikacin were identified. Most isolates were from patients with posttym panostomy tube placement otitis media or patients with cystic fibrosis who had received aminoglycoside therapy. Isolates were highly resista nt (MICs >1024 mu g/mL) to amikacin, kanamycin, gentamicin, tobramycin , and neomycin tall 2-deoxystreptamine aminoglycosides) but not to str eptomycin. Sequencing of their 16S ribosomal (r) RNA revealed that 16 (94%) of 17 had an A-->G mutation at position 1408, In vitro-selected amikacin-resistant mutants of M. abscessus and Mycobacterium chelonae had the same resistance phenotype, and 15 mutants all had the same A-- >G substitution at position 1408, Introducing an rRNA operon from Myco bacterium smegmatis with a mutated A-->G at this position into a singl e functional allelic rRNA mutant of M. smegmatis produced the same ami noglycoside resistance phenotype, These studies demonstrate this 16S r RNA mutation is responsible for amikacin resistance in M. abscessus, w hich has only one copy of the rRNA operon.