{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T19:02:11Z","timestamp":1785438131892,"version":"3.56.0"},"reference-count":32,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI152358"],"award-info":[{"award-number":["R01 AI152358"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R44 AI134190"],"award-info":[{"award-number":["R44 AI134190"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2026,4,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      New antibacterials are still needed to treat serious gram-positive hospital infections, including acute bacterial skin and skin structure infections and bloodstream infections. MRS-2541 is a novel type 1 methionyl-tRNA synthetase inhibitor highly selective for gram-positive bacteria. MRS-2541 was evaluated with multiple comparator antibiotics against a large panel of gram-positive organisms enriched with antibacterial-resistant phenotypes. MRS-2541 was the most potent agent against 45\n                      <jats:italic toggle=\"yes\">Staphylococcus aureus<\/jats:italic>\n                      (SA) (6 SAs, 27 methicillin-resistant\n                      <jats:italic toggle=\"yes\">Staphylococcus aureus<\/jats:italic>\n                      , and 12 vancomycin-intermediate\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      ) and 35 coagulase-negative staphylococci with MIC\n                      <jats:sub>90<\/jats:sub>\n                      values of 0.06 and 0.12 \u00b5g\/mL, respectively, which was superior to all comparators, including vancomycin, linezolid, and daptomycin. MRS-2541 was very potent against 15\n                      <jats:italic toggle=\"yes\">Enterococcus faecalis<\/jats:italic>\n                      (4-VRE) and 13\/15\n                      <jats:italic toggle=\"yes\">Enterococcus faecium<\/jats:italic>\n                      at \u22640.016 \u00b5g\/mL, with two insensitive\n                      <jats:italic toggle=\"yes\">faecium<\/jats:italic>\n                      strains (&gt;16 \u00b5g\/mL). MRS-2541 was less potent against\n                      <jats:italic toggle=\"yes\">Streptococcus<\/jats:italic>\n                      spp., with MIC\n                      <jats:sub>90<\/jats:sub>\n                      values vs\n                      <jats:italic toggle=\"yes\">S. pyogenes<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">S. pneumoniae<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">S. sanguinis<\/jats:italic>\n                      of 0.5 \u03bcg\/mL.\n                      <jats:italic toggle=\"yes\">S. agalactiae<\/jats:italic>\n                      and the viridans group streptococci were much less sensitive, with MIC\n                      <jats:sub>90<\/jats:sub>\n                      values of 8 to &gt;16 \u00b5g\/mL. These data support MRS-2541 as a new potential option for serious gram-positive hospital infections.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      Infections caused by antibiotic-resistant bacteria are inherently challenging to treat. Poor outcomes, including higher death rates, are associated with infections caused by antibiotic-resistant organisms. As a result, there is an urgent need for new antibiotics, particularly ones that act via novel mechanisms that evade established resistance mechanisms. In this paper, we provide new data about MRS-2541, a preclinical antibiotic that acts by inhibiting the bacterial methionyl-tRNA synthetase. We show that MRS-2541 has potent in vitro activity against diverse strains of\n                      <jats:italic toggle=\"yes\">Staphylococcus<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Streptococcus<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">Enterococcus<\/jats:italic>\n                      . For example, all 115 strains of\n                      <jats:italic toggle=\"yes\">Staphylococcus<\/jats:italic>\n                      spp. (including 27 methicillin-resistant\n                      <jats:italic toggle=\"yes\">Staphylococcus aureus<\/jats:italic>\n                      strains and 12 vancomycin-intermediate\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      strains) were fully susceptible to MRS-2541 with MICs of &lt;0.25 \u03bcg\/mL. The specific activity against gram-positive bacteria and sparing of gram-negative flora indicates that MRS-2541 may be less disruptive of intestinal microbiota than broad-spectrum antibiotics. MRS-2541 is a promising preclinical candidate for infections due to resistant gram-positive organisms.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.03615-25","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T13:33:37Z","timestamp":1773236017000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["<i>In vitro<\/i>\n                    activity of MRS-2541, a novel MetRS inhibitor, against a selection of resistant gram-positive organisms associated with serious hospital infections"],"prefix":"10.1128","volume":"14","author":[{"given":"John","family":"Domagala","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02hyqz930","id-type":"ROR","asserted-by":"publisher"}],"name":"TSRL Inc.","place":["Ann Arbor, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyedhameneh","family":"Jahanbakhsh","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02hyqz930","id-type":"ROR","asserted-by":"publisher"}],"name":"Microbiologics, Inc., Bacteriology and Mycology Center of Excellence","place":["Portage, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela K.","family":"Mendez","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02hyqz930","id-type":"ROR","asserted-by":"publisher"}],"name":"Microbiologics, Inc., Bacteriology and Mycology Center of Excellence","place":["Portage, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris M.","family":"Pillar","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02hyqz930","id-type":"ROR","asserted-by":"publisher"}],"name":"Microbiologics, Inc., Bacteriology and Mycology Center of Excellence","place":["Portage, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Marra","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02hyqz930","id-type":"ROR","asserted-by":"publisher"}],"name":"Microbiologics, Inc., Bacteriology and Mycology Center of Excellence","place":["Portage, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4878-1520","authenticated-orcid":true,"given":"David A.","family":"Hufnagel","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02hyqz930","id-type":"ROR","asserted-by":"publisher"}],"name":"Microbiologics, Inc., Bacteriology and Mycology Center of Excellence","place":["Portage, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora M. 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