Characterization of streptomycin resistance mechanisms among Mycobacterium tuberculosis isolates from patients in New York City

Abstract

From a collection of 367 isolates of Mycobacterium tuberculosis from patients in New York City in 1994, 45 isolates (12.3%) were resistant in vitro to 2 micrograms or more of streptomycin (SM) per ml. We further evaluated these isolates for levels of SM resistance and for mutations previously associated with resistance in the rpsL (S12 ribosomal protein) gene and the rrs (16S rRNA)-coding region. Twenty-four isolates, representing nine distinct patterns of susceptibility to antituberculosis drugs, were resistant to 500 micrograms of SM per ml and shared a common point mutation at nucleotide 128 in the rpsL gene. This mutation, which substitutes lysine for arginine in the S12 ribosomal binding protein, was not present in isolates with low-level SM resistance or in SM-susceptible control isolates. Among 20 isolates with low-level SM resistance, one possessed a substitution (C-->G865) in the 912 loop of the rrs gene. No mutations in the 530 loop of the rrs coding region were detected, suggesting the presence of an alternative SM resistance mechanism in 19 isolates. Single-strand conformation polymorphisms of mutants were readily detected by a nonradioactive gel screen.