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

In the last decade, invasive group A Streptococcus (iGAS) infections have doubled in the US, with equivalent increases in MLS B (macrolide, lincosamide, and streptogramin B)-resistance. The emm92 -type isolates carrying the erm (T) gene have been associated with an alarming emergence of iGAS infecti...

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Bibliographic Details
Published in:NPJ ANTIMICROBIALS AND RESISTANCE 2024-12, Vol.2 (1), p.44-13
Main Authors: Powell, Lillie M., Choi, Soo Jeon, Grund, Megan E., Demkowicz, Ryan, Berisio, Rita, LaSala, P. Rocco, Lukomski, Slawomir
Format: Article
Language:English
Subjects:
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Antibiotics
Bacteria
Biomedical and Life Sciences
Clindamycin
Combination therapy
DNA methylation
Enzymes
Erythromycin
Gene expression
Genes
Genotype & phenotype
Homelessness
Homology
Life Sciences
Microbiology
Mutation
Peptides
Phenotypes
Polymorphism
Production increases
Proteins
Regulatory sequences
Sequence analysis
Streptococcus
Streptococcus infections
Streptogramin B
Structural members
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Summary:In the last decade, invasive group A Streptococcus (iGAS) infections have doubled in the US, with equivalent increases in MLS B (macrolide, lincosamide, and streptogramin B)-resistance. The emm92 -type isolates carrying the erm (T) gene have been associated with an alarming emergence of iGAS infections in people who inject drugs or experience homelessness. Our goal was to elucidate the mechanisms behind inducible (iMLS B ) and constitutive (cMLS B ) resistance in emm92 isolates. Sequence analysis identified polymorphisms in the erm (T) regulatory region associated with cMLS B resistance. RT-qPCR and RNAseq revealed increased erm (T) mRNA levels in iMLS B isolates in response to erythromycin exposure, while cMLS B isolates exhibited high erm (T) expression independent from antibiotic exposure. Transcription results were coupled with shifting levels of ribosomal methylation. A homology model of the ErmT enzyme identified structural elements and residues conserved in methyltransferases. Delayed growth of iMLS B isolates cultured with erythromycin and increased clindamycin resistance in cMLS B isolates were observed.
ISSN:2731-8745
DOI:10.1038/s44259-024-00062-3