Mechanism of Resistance to Amikacin and Kanamycin in Mycobacterium tuberculosis

ABSTRACT An A1400G mutation of the rrs gene was identified inMycobacterium tuberculosis (MTB) strain ATCC 35827 and in 13 MTB clinical isolates resistant to amikacin-kanamycin (MICs, >128 μg/ml). High-level cross-resistance may result from such a mutation since MTB has a single copy of the rrs gene. Another mechanism(s) may account for high-level amikacin-kanamycin resistance in two mutants and lower levels of resistance in four clinical isolates, all lacking the A1400G mutation.

[1]  B. Heym,et al.  Implications of multidrug resistance for the future of short-course chemotherapy of tuberculosis: a molecular study , 1994, The Lancet.

[2]  T. Prammananan,et al.  Introducing mutations into a chromosomal rRNA gene using a genetically modified eubacterial host with a single rRNA operon , 1996, Molecular microbiology.

[3]  S. Cole,et al.  Streptomycin resistance in mycobacteria , 1994, Antimicrobial Agents and Chemotherapy.

[4]  Harry F. Noller,et al.  Interaction of antibiotics with functional sites in 16S ribosomal RNA , 1987, Nature.

[5]  E. Böttger,et al.  Genetic alterations in streptomycin-resistant Mycobacterium tuberculosis: mapping of mutations conferring resistance , 1994, Antimicrobial Agents and Chemotherapy.

[6]  G. Bai,et al.  Molecular mechanisms of multiple drug resistance in clinical isolates of Mycobacterium tuberculosis. , 1995, The Journal of infectious diseases.

[7]  G. Bai,et al.  The rpsL gene and streptomycin resistance in single and multiple drug‐resistant strains of Mycobacterium tuberculosis , 1993, Molecular microbiology.

[8]  E. Cundliffe,et al.  Sites of action of two ribosomal RNA methylases responsible for resistance to aminoglycosides. , 1987, Journal of molecular biology.

[9]  E. Böttger,et al.  Molecular basis of streptomycin resistance in Mycobacterium tuberculosis: alterations of the ribosomal protein S12 gene and point mutations within a functional 16S ribosomal RNA pseudoknot , 1993, Molecular microbiology.

[10]  H. Noller,et al.  Mutations in 16S ribosomal RNA disrupt antibiotic–RNA interactions. , 1989, The EMBO journal.

[11]  J. T. Crawford,et al.  Strain identification of Mycobacterium tuberculosis by DNA fingerprinting: recommendations for a standardized methodology , 1993, Journal of clinical microbiology.

[12]  H. Noller,et al.  Rapid chemical probing of conformation in 16 S ribosomal RNA and 30 S ribosomal subunits using primer extension. , 1986, Journal of molecular biology.

[13]  J. T. Crawford,et al.  Characterization of streptomycin resistance mechanisms among Mycobacterium tuberculosis isolates from patients in New York City , 1996, Antimicrobial agents and chemotherapy.

[14]  P. Fujiwara,et al.  Tuberculosis in New York City. , 1999, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[15]  D. Girling,et al.  Amikacin in the treatment of pulmonary tuberculosis. , 1983, Tubercle.

[16]  J. Douglass,et al.  A ribosomal gene mutation in streptomycin-resistant Mycobacterium tuberculosis isolates. , 1993, The Journal of infectious diseases.

[17]  R. Cox,et al.  The nucleotide sequence of the promoter, 16S rRNA and spacer region of the ribosomal RNA operon of Mycobacterium tuberculosis and comparison with Mycobacterium leprae precursor rRNA. , 1992, Journal of general microbiology.

[18]  M. Tsukamura,et al.  Cross-resistant relationships among the aminoglucoside antibiotics in Mycobacterium tuberculosis. , 1975, Journal of general microbiology.

[19]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .