CRISPR-Cas-associated SCCmec Variants in Methicillin-resistant Staphylococcus aureus Evade Rapid Diagnostic Detection.

Podkowik, Magdalena; Tillman, Alice; Takats, Courtney; Carion, Heloise; Putzel, Gregory; McWilliams, Julian; See, Benjamin; Wang, Guiqing et al. · J Infect Dis · 2026

case_series · Level IV

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Abstract

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.

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