Streptomycin resistance and lineage-specific polymorphisms in Mycobacterium tuberculosis gidB gene

Mutations related to streptomycin-resistance in the rpsL and rrs genes are well known and can explain about 70% of this phenotypic resistance. Recently, the gidB gene was found to be associated with low level streptomycin-resistance in Mycobacterium tuberculosis. Mutations in gidB have been reported with high frequency, and this gene appears to be very polymorphic, with frameshift and point mutations occurring in streptomycin-susceptible and streptomycin-resistant strains. In this study, mutations in gidB appeared in 27% of streptomycin-resistant strains that contained no mutations in the rpsL or rrs genes and were associated with low-level streptomycin-resistance. However, the association of certain mutations in gidB with streptomycin-resistance needs to be further investigated as we also found mutations in gidB in streptomycin-susceptible strains. This occurred only when the strain was resistant to rifampicin and isoniazid. Two specific mutations appear very frequently in this and other studies in streptomycin-susceptible and resistant strains, these mutations were not considered as related to streptomycin-resistance, but as a polymorphism. We stratified the strains according to the different phylogenetic lineages and showed that the gidB(16) polymorphism (16G allele) was exclusively present in the Latin American Mediterranean genotype, while the gidB(92) polymorphism (92C allele) was associated with the Beijing lineage in another population. In the sample studied, the two characterized single nucleotide polymorphisms could distinguish LAM and Beijing lineages from the other lineages.