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      GidB mutation as a phylogenetic marker for Q1 cluster Mycobacterium tuberculosis isolates and intermediate-level streptomycin resistance determinant in Lisbon, Portugal.

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          Abstract

          Development of streptomycin resistance in Mycobacterium tuberculosis is usually associated with mutations in rpsL and rrs genes, although up to 50% of clinical streptomycin-resistant isolates may present no mutation in either of these genes. In the present report we investigate the role of gidB gene mutations in streptomycin resistance. We have analyzed 52 streptomycin-resistant and 30 streptomycin-susceptible Mycobacterium tuberculosis clinical isolates by sequencing and endonuclease analysis of the gidB and rpsL genes. All clinical isolates were genotyped by 12-loci MIRU-VNTR. The gidB gene of 18 streptomycin-resistant isolates was sequenced and four missense mutations were found: F12L (1/18), L16R (18/18), A80P (4/18) and S100F (18/18). The remaining isolates were screened by endonuclease analysis for mutations A80P in the gidB gene and K43R in the rpsL gene. Overall, mutation A80P in the gidB gene was found in eight streptomycin-resistant isolates and 11 streptomycin-susceptible multidrug-resistant isolates. Also noteworthy, is the fact that gidB mutations were only present in isolates without rpsL and rrs mutations, all from genetic cluster Q1. Streptomycin quantitative drug susceptibility testing showed that isolates carrying the gidB A80P mutation were streptomycin intermediate-level resistant and that standard drug susceptibility testing yielded inconsistent results, probably due to borderline resistance. We conclude that gidB mutations may explain the high number of streptomycin-resistant strains with no mutation in rpsL or rrs. These mutations might occasionally confer low-level streptomycin resistance that will go undetected in standard susceptibility testing.

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          Author and article information

          Journal
          Clin. Microbiol. Infect.
          Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases
          Wiley
          1469-0691
          1198-743X
          May 2014
          : 20
          : 5
          Affiliations
          [1 ] Faculdade de Farmácia, Centro de Patogénese Molecular, URIA, Universidade de Lisboa, Lisboa, Portugal.
          Article
          S1198-743X(14)60088-4
          10.1111/1469-0691.12392
          24102832
          2e8469e4-a659-4a0b-a724-2cd25f9fb3f1
          History

          rrs,M/XDR-TB,resistance level,rpsL
          rrs, M/XDR-TB, resistance level, rpsL

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