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; Munoz-Gomez, Sigridh; Otto, Caitlin; Drlica, Karl; Marraffini, Luciano; Pironti, Alejandro; Hochman, Sarah; Kerantzas, Christopher; Shopsin, Bo
Rapid molecular assays guiding treatment of methicillin-resistant Staphylococcus aureus (MRSA) 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 2,432 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.
PMID: 41254867
ISSN: 1537-6613
CID: 5975822