CRISPR-Cas–associated SCC <i>mec</i> Variants in Methicillin-resistant <i>Staphylococcus aureus</i> Evade Rapid Diagnostic Detection
Rapid molecular assays guiding treatment of methicillin-resistant Staphylococcus aureus detect SCCmec (Xpert) or the SCCmec-orfX junction (BCID2). Sequence variation in this region can disrupt primer binding, yielding false-negative results. Investigation of a missed bloodstream infection linked escape to a CRISPR-Cas-associated SCCmec variant, leading to identification of 64 variants from 45 patients-2% of 2432 screened. Misdiagnosis was restricted to clonal complex 5, a hospital-associated lineage; 11 of 40 SCCmec/junctions evaded detection by BCID2 or Xpert. Variants had mecA instability and circulated in healthcare settings. Our findings reveal a unique escape mechanism and underscore a threat to diagnostic accuracy.
Authors
- J. Michael McWilliams (ORCID: https://orcid.org/0000-0002-4866-862X)
- Sarah Hochman (ORCID: https://orcid.org/0000-0003-2011-0453)
- Benjamin See (ORCID: https://orcid.org/0009-0000-6227-9666)
- Héloïse Carion
- Courtney Takats (ORCID: https://orcid.org/0000-0001-5116-7968)
- Sigridh Muñoz-Gómez (ORCID: https://orcid.org/0000-0002-8836-2676)
- Caitlin Otto (ORCID: https://orcid.org/0000-0002-1894-2480)
- Karl Drlica (ORCID: https://orcid.org/0000-0002-4831-6384)
- Christopher A. Kerantzas (ORCID: https://orcid.org/0000-0002-6745-9452)
- Gregory Putzel (ORCID: https://orcid.org/0000-0002-5211-2608)
- Guiqing Wang (ORCID: https://orcid.org/0000-0001-6590-5394)
- Alejandro Pironti (ORCID: https://orcid.org/0000-0002-7759-6776)
- Luciano A. Marraffini (ORCID: https://orcid.org/0000-0002-9163-0969)
- Alice Tillman
- Bo Shopsin (ORCID: https://orcid.org/0009-0001-7729-8584)
- Magdalena Podkowik (ORCID: https://orcid.org/0009-0005-6772-3697)
Institutions
- Rutgers, The State University of New Jersey (US)
- Howard Hughes Medical Institute (US)
- Long Island University (US)
- New York Genome Center (US)
- New York University (US)
- Rockefeller University (US)
Publication Details
- Journal
- The Journal of Infectious Diseases
- Published
- 2025-11-15
- DOI
- https://doi.org/10.1093/infdis/jiaf575
- Primary Topic
- CRISPR and Genetic Engineering
- Type
- article
- Field-Weighted Citation Impact
- 0.00