Dataset Information

Two distinct genetic elements are responsible for erm(TR)-mediated erythromycin resistance in tetracycline-susceptible and tetracycline-resistant strains of Streptococcus pyogenes.

ABSTRACT: In Streptococcus pyogenes, inducible erythromycin (ERY) resistance is due to posttranscriptional methylation of an adenine residue in 23S rRNA that can be encoded either by the erm(B) gene or by the more recently described erm(TR) gene. Two erm(TR)-carrying genetic elements, showing extensive DNA identities, have thus far been sequenced: ICE10750-RD.2 (?49 kb) and Tn1806 (?54 kb), from tetracycline (TET)-susceptible strains of S. pyogenes and Streptococcus pneumoniae, respectively. However, TET resistance, commonly mediated by the tet(O) gene, is widespread in erm(TR)-positive S. pyogenes. In this study, 23 S. pyogenes clinical strains with erm(TR)-mediated ERY resistance-3 TET susceptible and 20 TET resistant-were investigated. Two erm(TR)-carrying elements sharing only a short, high-identity erm(TR)-containing core sequence were comprehensively characterized: ICESp1108 (45,456 bp) from the TET-susceptible strain C1 and ICESp2905 (65,575 bp) from the TET-resistant strain iB21. While ICESp1108 exhibited extensive identities to ICE10750-RD.2 and Tn1806, ICESp2905 showed a previously unreported genetic organization resulting from the insertion of separate erm(TR)- and tet(O)-containing fragments in a scaffold of clostridial origin. Transferability by conjugation of the erm(TR) elements from the same strains used in this study had been demonstrated in earlier investigations. Unlike ICE10750-RD.2 and Tn1806, which are integrated into an hsdM chromosomal gene, both ICESp1108 and ICESp2905 shared the chromosomal integration site at the 3' end of the conserved rum gene, which is an integration hot spot for several mobile streptococcal elements. By using PCR-mapping assays, erm(TR)-carrying elements closely resembling ICESp1108 and ICESp2905 were shown in the other TET-susceptible and TET-resistant test strains, respectively.

SUBMITTER: Brenciani A

PROVIDER: S-EPMC3088260 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Two distinct genetic elements are responsible for erm(TR)-mediated erythromycin resistance in tetracycline-susceptible and tetracycline-resistant strains of Streptococcus pyogenes.

Brenciani Andrea A Tiberi Erika E Bacciaglia Alessandro A Petrelli Dezemona D Varaldo Pietro E PE Giovanetti Eleonora E

Antimicrobial agents and chemotherapy 20110222 5

In Streptococcus pyogenes, inducible erythromycin (ERY) resistance is due to posttranscriptional methylation of an adenine residue in 23S rRNA that can be encoded either by the erm(B) gene or by the more recently described erm(TR) gene. Two erm(TR)-carrying genetic elements, showing extensive DNA identities, have thus far been sequenced: ICE10750-RD.2 (∼49 kb) and Tn1806 (∼54 kb), from tetracycline (TET)-susceptible strains of S. pyogenes and Streptococcus pneumoniae, respectively. However, TET ...[more]

PMID: 21343455

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Project description:This study was directed at characterizing the genetic elements carrying the methylase gene erm(B), encoding ribosome modification-mediated resistance to macrolide, lincosamide, and streptogramin B (MLS) antibiotics, in Streptococcus pyogenes. In this species, erm(B) is responsible for MLS resistance in constitutively resistant isolates (cMLS phenotype) and in a subset (iMLS-A) of inducibly resistant isolates. A total of 125 erm(B)-positive strains were investigated, 81 iMLS-A (uniformly tetracycline susceptible) and 44 cMLS (29 tetracycline resistant and 15 tetracycline susceptible). Whereas all tetracycline-resistant isolates carried the tet(M) gene, tet(M) sequences were also detected in most tetracycline-susceptible isolates (81/81 iMLS-A and 7/15 cMLS). In 2 of the 8 tet(M)-negative cMLS isolates, erm(B) was carried by a plasmid-located Tn917-like transposon. erm(B)- and tet(M)-positive isolates were tested by PCR for the presence of genes int (integrase), xis (excisase), and tndX (resolvase), associated with conjugative transposons of the Tn916 family. In mating experiments using representatives of different combinations of phenotypic and genotypic characteristics as donors, erm(B) and tet(M) were consistently cotransferred, suggesting their linkage in individual genetic elements. The linkage was confirmed by pulsed-field gel electrophoresis and hybridization studies, and different elements, variably associated with the different phenotypes/genotypes, were detected and characterized by amplification and sequencing experiments. A previously unreported genetic organization, observed in all iMLS-A and some cMLS isolates, featured an erm(B)-containing DNA insertion into the tet(M) gene of a defective Tn5397, a Tn916-related transposon. This new element was designated Tn1116. Genetic elements not previously described in S. pyogenes also included Tn6002, an unpublished transposon whose complete sequence is available in GenBank, and Tn3872, a composite element resulting from the insertion of the Tn917 transposon into Tn916 [associated with a tet(M) gene expressed in some cMLS isolates and silent in others]. The high frequency of association between a tetracycline-susceptible phenotype and tet(M) genes suggests that transposons of the Tn916 family, so far typically associated solely with a tetracycline-resistant phenotype, may be more widespread in S. pyogenes than currently believed.

Project description:Streptococcus pyogenes, also known as group A Streptococcus (GAS), is one of the top 10 infectious causes of death worldwide. Macrolide and tetracycline resistant GAS has emerged as a major health concern in China coinciding with an ongoing scarlet fever epidemic. Furthermore, increasing rates of fluoroquinolone (FQ) non-susceptibility within GAS from geographical regions outside of China has also been reported. Fluoroquinolones are the third most commonly prescribed antibiotic in China and is an therapeutic alternative for multi-drug resistant GAS. The purpose of this study was to investigate the epidemiological and molecular features of GAS fluoroquinolone (FQ) non-susceptibility in Shanghai, China. GAS (n = 2,258) recovered between 2011 and 2016 from children and adults were tested for FQ-non-susceptibility. Efflux phenotype and mutations in parC, parE, gyrA, and gyrB were investigated and genetic relationships were determined by emm typing, pulsed-field gel electrophoresis and phylogenetic analysis. The frequency of GAS FQ-non-susceptibility was 1.3% (30/2,258), with the phenotype more prevalent in GAS isolated from adults (14.3%) than from children (1.2%). Eighty percent (24/30) of FQ-non-susceptible isolates were also resistant to both macrolides (ermB) and tetracycline (tetM) including the GAS sequence types emm12, emm6, emm11, and emm1. Genomic fingerprinting analysis of the 30 isolates revealed that non-susceptibility may arise in various genetic backgrounds even within a single emm type. No efflux phenotype was observed in FQ non-susceptible isolates, and molecular analysis of the quinolone resistance-determining regions (QRDRs) identified several sequence polymorphisms in ParC and ParE, and none in GyrA and GyrB. Expansion of this analysis to 152 publically available GAS whole genome sequences from Hong Kong predicted 7.9% (12/152) of Hong Kong isolates harbored a S79F ParC mutation, of which 66.7% (8/12) were macrolide and tetracycline resistant. Phylogenetic analysis of the parC QRDR sequences suggested the possibility that FQ resistance may be acquired through inter-species lateral gene transfer. This study reports the emergence of macrolide, tetracycline, and fluoroquinolone multidrug-resistant clones across several GAS emm types including emm1 and emm12, warranting continual surveillance given the extensive use of fluoroquinolones in clinical use.

Dataset Information

Two distinct genetic elements are responsible for erm(TR)-mediated erythromycin resistance in tetracycline-susceptible and tetracycline-resistant strains of Streptococcus pyogenes.

Publications

Two distinct genetic elements are responsible for erm(TR)-mediated erythromycin resistance in tetracycline-susceptible and tetracycline-resistant strains of Streptococcus pyogenes.

Similar Datasets

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