Emergence of transferable daptomycin resistance in Gram-positive bacteria
Abstract Daptomycin (DAP) is a last-resort antibiotic to treat infections by multiresistant Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci. DAP resistance and clinical treatment failure has been associated with adaptive chro...
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| Format: | Article |
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Nature Portfolio
2025-04-01
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| Series: | npj Antimicrobials and Resistance |
| Online Access: | https://doi.org/10.1038/s44259-025-00109-z |
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| author | Tessa Marciniak Lukas Kirchner Silver A. Wolf Birgit Walther Thorsten Bischler Justin Nyasinga Revathi Gunturu Torsten Semmler Tom Gräfenhan Andrew Whitelaw Oliver Scherf-Clavel Ulrike Holzgrabe Wilma Ziebuhr |
| author_facet | Tessa Marciniak Lukas Kirchner Silver A. Wolf Birgit Walther Thorsten Bischler Justin Nyasinga Revathi Gunturu Torsten Semmler Tom Gräfenhan Andrew Whitelaw Oliver Scherf-Clavel Ulrike Holzgrabe Wilma Ziebuhr |
| author_sort | Tessa Marciniak |
| collection | DOAJ |
| description | Abstract Daptomycin (DAP) is a last-resort antibiotic to treat infections by multiresistant Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci. DAP resistance and clinical treatment failure has been associated with adaptive chromosomal mutations, but so far not with transmissible resistance traits. Here we report for the first time an acquired DAP-R determinant (named drc) that we detected in a livestock-associated Mammaliicoccus sciuri isolate. drc consists of a two-gene operon (drcAB) that is controlled by an adjacent two-component system (drcRS). The DrcAB proteins, which mediate DAP inactivation, are similar to BceAB-like antimicrobial peptide transporters of Gram-positives, but are distinct from currently known systems. The mobile drc locus is functional in various bacterial backgrounds, including MRSA. It circulates primarily among Gram-positives in the environment, but also in commensal staphylococci and enterococci, suggesting a risk of transmission into pathogens and emphasizing the importance of low and apathogenic microorganisms as resistance gene reservoirs. |
| format | Article |
| id | doaj-art-2f16a16dae164be5aad24f1b440e3ee5 |
| institution | OA Journals |
| issn | 2731-8745 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Antimicrobials and Resistance |
| spelling | doaj-art-2f16a16dae164be5aad24f1b440e3ee52025-08-20T02:19:58ZengNature Portfolionpj Antimicrobials and Resistance2731-87452025-04-01311910.1038/s44259-025-00109-zEmergence of transferable daptomycin resistance in Gram-positive bacteriaTessa Marciniak0Lukas Kirchner1Silver A. Wolf2Birgit Walther3Thorsten Bischler4Justin Nyasinga5Revathi Gunturu6Torsten Semmler7Tom Gräfenhan8Andrew Whitelaw9Oliver Scherf-Clavel10Ulrike Holzgrabe11Wilma Ziebuhr12Institute of Molecular Infection Biology, University of WurzburgInstitute for Pharmacy and Food Chemistry, University of WurzburgGenome Competence Centre (MF1), Robert Koch InstituteMicrobiological Risks (II 1.4), German Environment AgencyCore Unit Systems Medicine, University of WurzburgThe Aga Khan University HospitalThe Aga Khan University HospitalGenome Competence Centre (MF1), Robert Koch InstituteCore Unit Systems Medicine, University of WurzburgDivision of Medical Microbiology, Stellenbosch University, Cape Town and National Health Laboratory Service, Tygerberg HospitalDepartment of Pharmacy, Clinical Pharmacy and Pharmacotherapy, Ludwig-Maximilians-UniversityInstitute for Pharmacy and Food Chemistry, University of WurzburgInstitute of Molecular Infection Biology, University of WurzburgAbstract Daptomycin (DAP) is a last-resort antibiotic to treat infections by multiresistant Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci. DAP resistance and clinical treatment failure has been associated with adaptive chromosomal mutations, but so far not with transmissible resistance traits. Here we report for the first time an acquired DAP-R determinant (named drc) that we detected in a livestock-associated Mammaliicoccus sciuri isolate. drc consists of a two-gene operon (drcAB) that is controlled by an adjacent two-component system (drcRS). The DrcAB proteins, which mediate DAP inactivation, are similar to BceAB-like antimicrobial peptide transporters of Gram-positives, but are distinct from currently known systems. The mobile drc locus is functional in various bacterial backgrounds, including MRSA. It circulates primarily among Gram-positives in the environment, but also in commensal staphylococci and enterococci, suggesting a risk of transmission into pathogens and emphasizing the importance of low and apathogenic microorganisms as resistance gene reservoirs.https://doi.org/10.1038/s44259-025-00109-z |
| spellingShingle | Tessa Marciniak Lukas Kirchner Silver A. Wolf Birgit Walther Thorsten Bischler Justin Nyasinga Revathi Gunturu Torsten Semmler Tom Gräfenhan Andrew Whitelaw Oliver Scherf-Clavel Ulrike Holzgrabe Wilma Ziebuhr Emergence of transferable daptomycin resistance in Gram-positive bacteria npj Antimicrobials and Resistance |
| title | Emergence of transferable daptomycin resistance in Gram-positive bacteria |
| title_full | Emergence of transferable daptomycin resistance in Gram-positive bacteria |
| title_fullStr | Emergence of transferable daptomycin resistance in Gram-positive bacteria |
| title_full_unstemmed | Emergence of transferable daptomycin resistance in Gram-positive bacteria |
| title_short | Emergence of transferable daptomycin resistance in Gram-positive bacteria |
| title_sort | emergence of transferable daptomycin resistance in gram positive bacteria |
| url | https://doi.org/10.1038/s44259-025-00109-z |
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