A Point Mutation Associated with Bacterial Macrolide Resistance Is Present in Both 23S rRNA Genes of an Erythromycin-Resistant
            <b>
              <i>Treponema pallidum</i>
              Clinical Isolate
            </b>

Stamm, Lola V.; Bergen, Heather L.

doi:10.1128/aac.44.3.806-807.2000

Cited by 114 publications

(84 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Variant DNA segments located adjacent to the tprD gene non-reciprocally recombine with the variable regions (V1-V7) of the tprK gene in the expression site to generate new TprK mosaic proteins. (120). Clinical failures following azithromycin treatment in San Francisco triggered examination of T. pallidum strains from several geographical regions, revealing the presence of the A2058G mutation in 11%-88% of T. pallidum samples (121,122).…”

Section: Figurementioning

confidence: 99%

Syphilis: using modern approaches to understand an old disease

Lukehart²

2011

J. Clin. Invest.

201

168

View full text Add to dashboard Cite

Syphilis is a fascinating and perplexing infection, with protean clinical manifestations and both diagnostic and management ambiguities. Treponema pallidum subsp. pallidum, the agent of syphilis, is challenging to study in part because it cannot be cultured or genetically manipulated. Here, we review recent progress in the application of modern molecular techniques to understanding the biological basis of this multistage disease and to the development of new tools for diagnosis, for predicting efficacy of treatment with alternative antibiotics, and for studying the transmission of infection through population networks.

show abstract

Section: Figurementioning

confidence: 99%

Syphilis: using modern approaches to understand an old disease

Lukehart²

2011

J. Clin. Invest.

201

168

View full text Add to dashboard Cite

show abstract

“…The first point mutation associated with macrolide treatment failure in Treponema pallidum strains was originally reported as an adenine-to-guanine transition (A2058G), cognate to the position in Escherichia coli (7,8), in both copies of the 23S rRNA gene (9), and the functional macrolide resistance was confirmed in vivo by using a rabbit model infected with an azithromycin-or erythromycin-resistant T. pallidum strain containing the mutation (7). Recently, a second point mutation (A2059G) in the same gene was also found to be associated with macrolide treatment failure in syphilis patients (10).…”

Section: Detection Of the A2058g And A2059g 23s Rrna Gene Point Mutatmentioning

confidence: 99%

Detection of the A2058G and A2059G 23S rRNA Gene Point Mutations Associated with Azithromycin Resistance in Treponema pallidum by Use of a TaqMan Real-Time Multiplex PCR Assay

et al. 2013

View full text Add to dashboard Cite

Macrolide treatment failure in syphilis patients is associated with a single point mutation (either A2058G or A2059G) in both copies of the 23S rRNA gene in Treponema pallidum strains. The conventional method for the detection of both point mutations uses nested PCR combined with restriction enzyme digestions, which is laborious and time-consuming. We initially developed a TaqMan-based real-time duplex PCR assay for detection of the A2058G mutation, and upon discovery of the A2059G mutation, we modified the assay into a triplex format to simultaneously detect both mutations. The point mutations detected by the realtime triplex PCR were confirmed by pyrosequencing. A total of 129 specimens PCR positive for T. pallidum that were obtained from an azithromycin resistance surveillance study conducted in the United States were analyzed. Sixty-six (51.2%) of the 129 samples with the A2058G mutation were identified by both real-time PCR assays. Of the remaining 63 samples that were identified as having a macrolide-susceptible genotype by the duplex PCR assay, 17 (27%) were found to contain the A2059G mutation by the triplex PCR. The proportions of macrolide-susceptible versus -resistant genotypes harboring either the A2058G or the A2059G mutation among the T. pallidum strains were 35.6, 51.2, and 13.2%, respectively. None of the T. pallidum strains examined had both point mutations. The TaqMan-based real-time triplex PCR assay offers an alternative to conventional nested PCR and restriction fragment length polymorphism analyses for the rapid detection of both point mutations associated with macrolide resistance in T. pallidum.

show abstract

“…This finding indicates the potential of using the above stated chromosomal loci in a detailed genetic identification of clinical samples. Although the typing of 23S rDNA locus revealed three genotypes, one encoding sensitivity to macrolide antibiotics and two coding for macrolide resistance (A2058G and A2059G mutations, respectively; Lukehart et al, 2004;Matějková et al, 2009;Stamm & Bergen, 2000), their use in molecular typing is probably limited by the fact that these mutations can be selected by use of macrolide antibiotics in a population. In the Czech Republic, more than 35% of clinical samples were found to contain a mutation encoding resistance to macrolide antibiotics (Flasarová et al, unpublished results).…”

Section: Pcr Analyses Of Clinical Samplesmentioning

confidence: 99%