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Regulation of erm(T) MLSB phenotype expression in the emergent emm92 type group A Streptococcus

Lillie M Powell1, Soo Jeon Choi1, Megan E Grund1

  • 1Department of Microbiology, Immunology, and Cell Biology, West Virginia University School of Medicine, Morgantown, WV, USA.

Npj Antimicrobials and Resistance
|January 22, 2025
PubMed

Insights

Invasive group A Streptococcus infections are rising, linked to MLSB-resistance. Researchers uncovered genetic and expression changes in the erm(T) gene, explaining both inducible and constitutive macrolide resistance mechanisms in emm92 isolates.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Genetics

Background:

  • Invasive group A Streptococcus (iGAS) infections have doubled in the US over the past decade.
  • This increase correlates with rising MLSB (macrolide, lincosamide, streptogramin B) resistance.
  • emm92-type isolates with the erm(T) gene are emerging in vulnerable populations.

Purpose of the Study:

  • To investigate the molecular mechanisms of inducible (iMLSB) and constitutive (cMLSB) MLSB resistance in emm92 iGAS isolates.
  • To understand the role of the erm(T) gene in conferring antibiotic resistance.

Main Methods:

  • Sequence analysis of the erm(T) regulatory region.
  • Quantitative reverse transcription PCR (RT-qPCR) and RNA sequencing (RNAseq) to measure erm(T) mRNA levels.
  • Homology modeling of the ErmT enzyme.

Main Results:

  • Specific polymorphisms in the erm(T) regulatory region were linked to cMLSB resistance.
  • iMLSB isolates showed increased erm(T) expression upon erythromycin exposure.
  • cMLSB isolates displayed high erm(T) expression independent of antibiotic presence.
  • Antibiotic exposure affected ribosomal methylation levels and bacterial growth rates.

Conclusions:

  • Genetic variations in the erm(T) gene's regulatory region dictate MLSB resistance phenotypes in emm92 iGAS.
  • Understanding these resistance mechanisms is crucial for managing iGAS infections, particularly in at-risk populations.

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