{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T02:54:00Z","timestamp":1783997640763,"version":"3.55.0"},"reference-count":106,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Macrolide overuse and resulting resistance crippled the applicability of one of the most important and successful classes of antibiotics. The rising incidence of invasive infections caused by \u03b2\u2010hemolytic group A and group B streptococci have been paralleled with marked increases in erythromycin and clindamycin resistance. As a result, resistant invasive group A and group B\n                    <jats:italic>Streptococcus<\/jats:italic>\n                    infections have been classified by the CDC as a concerning level threat since 2019. Acquisition of erythromycin resistance methylase (\n                    <jats:italic>erm<\/jats:italic>\n                    ) genes is a major contributor of the MLS\n                    <jats:sub>B<\/jats:sub>\n                    [macrolide (i.e., erythromycin), lincosamide (i.e., clindamycin), and streptogramin B] resistance phenotype in US isolates. The\n                    <jats:italic>erm<\/jats:italic>\n                    \u2010encoded enzymes utilize the methyl\u2010group from S\u2010adenosyl\u2010L\u2010methionine (SAM) to methylate the adenosine A2058 residue of bacterial ribosomal RNA, which serves as the overlapping rRNA target site for the three MLS\n                    <jats:sub>B<\/jats:sub>\n                    classes of antibiotics. The major mechanism that regulates Erm methyltransferase production is translational attenuation in the 5\u2032 regulatory region upstream of the\n                    <jats:italic>erm<\/jats:italic>\n                    coding sequence. The 5\u2032 regulatory region of\n                    <jats:italic>erm<\/jats:italic>\n                    includes at least one short leader peptide\n                    <jats:italic>erm<\/jats:italic>\n                    L, with the leader peptide ribosome binding site (SD1), non\u2010translational stem\u2010loop structures, and the\n                    <jats:italic>erm<\/jats:italic>\n                    start codon with its ribosome binding site (SD2). Binding of a macrolide antibiotic to the ribosome causes stalling during translation of the\n                    <jats:italic>erm<\/jats:italic>\n                    L peptide, which disrupts and alters the formation of inhibitory mRNA hairpins in the\n                    <jats:italic>erm<\/jats:italic>\n                    5\u2032 regulatory region, thereby releasing the\n                    <jats:italic>erm<\/jats:italic>\n                    SD2\u2010site from the posterior stem\u2010loop hairpin, thus allowing Erm protein translation. The streptococcal ErmA, ErmB, and ErmT proteins have conserved structures with primary sequence conservation of residues involved in SAM\u2010 and rRNA\u2010binding activity, as well as a high\u2010level of structural conservation. However, the observed variation in the\n                    <jats:italic>erm<\/jats:italic>\n                    5\u2032 regulatory region sequences, transcript expression, and ribosome methylation levels associated with these genes and proteins underscore the regulatory complexity of Erm expression. This review aims to present insights into mechanisms of Erm\u2010mediated resistance, trends in streptococcal epidemiology and treatment, and progress in the development of improved MLS\n                    <jats:sub>B<\/jats:sub>\n                    drugs that effectively block\n                    <jats:italic>erm<\/jats:italic>\n                    \u2010mediated resistance.\n                  <\/jats:p>","DOI":"10.1111\/mmi.70078","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T07:40:21Z","timestamp":1778830821000},"page":"47-59","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Complexity of\n                    <scp>\n                      <i>erm<\/i>\n                    <\/scp>\n                    \u2010Mediated Resistance: Structural and Functional Perspectives From \u03b2\u2010Hemolytic Streptococci"],"prefix":"10.1111","volume":"126","author":[{"given":"Lillie M.","family":"Powell","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology, and Cell Biology West Virginia University School of Medicine  Morgantown West Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Berisio","sequence":"additional","affiliation":[{"name":"Institute of Biostructure and Bioimaging National Research Council, CNR  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. Rocco","family":"LaSala","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of Connecticut Health  Farmington Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5159-1838","authenticated-orcid":false,"given":"Slawomir","family":"Lukomski","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Cell Biology West Virginia University School of Medicine  Morgantown West Virginia USA"},{"name":"West Virginia Clinical and Translational Institute West Virginia University School of Medicine  Morgantown West Virginia 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