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<sub>B</sub> (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<sub>B</sub>) and constitutive (cMLS<sub>B</sub>) resistance in emm92 isolates. Sequence analysis identified polymorphisms in the erm(T) regulatory region associated with cMLS<sub>B</sub> resistance. RT-qPCR and RNAseq revealed increased erm(T) mRNA levels in iMLS<sub>B</sub> isolates in response to erythromycin exposure, while cMLS<sub>B</sub> 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<sub>B</sub> isolates cultured with erythromycin and increased clindamycin resistance in cMLS<sub>B</sub> isolates were observed.
Authors
- Lillie M. Powell (ORCID: https://orcid.org/0000-0003-1392-4635)
- Soo Jeon Choi (ORCID: https://orcid.org/0000-0002-7030-7230)
- Sławomir Łukomski (ORCID: https://orcid.org/0000-0002-5159-1838)
- Megan E. Grund (ORCID: https://orcid.org/0000-0003-4103-3151)
- Rita Berisio (ORCID: https://orcid.org/0000-0001-5025-6483)
- Ryan Demkowicz (ORCID: https://orcid.org/0000-0002-5402-1873)
- P. Rocco LaSala (ORCID: https://orcid.org/0000-0002-8720-3964)
Institutions
- West Virginia University (US)
- University of Connecticut (US)
- West Virginia University Hospitals (US)
- Institute of Biostructure and Bioimaging (IT)
- National Research Council (IT)
- UConn Health (US)
Publication Details
- Journal
- npj Antimicrobials and Resistance
- Published
- 2024-11-29
- DOI
- https://doi.org/10.1038/s44259-024-00062-3
- Citations
- 5
- Primary Topic
- Streptococcal Infections and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 2.71
Funders
- West Virginia Clinical and Translational Science Institute
- National Institutes of Health
- Centers for Disease Control and Prevention
- National Institute of General Medical Sciences