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

## TL;DR

Some methicillin-resistant Staphylococcus aureus clones evade rapid diagnostic tests due to a CRISPR-Cas linked SCCmec variant, risking misdiagnosis and improper treatment.

## Contribution

The study reveals a novel CRISPR-Cas–associated SCCmec variant that causes false-negative results in rapid MRSA diagnostics.

## Key findings

- A CRISPR-Cas–linked SCCmec variant was identified in 64 MRSA clones from 45 patients.
- The variant evades detection by Xpert and BCID2 assays, leading to false-negative results.
- The variant is associated with mecA instability and is prevalent in healthcare settings.

## 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.

This study identifies methicillin-resistant Staphylococcus aureus clones carrying a CRISPR-Cas–linked SCCmec variant that escapes detection by rapid, point-of-care molecular diagnostics that are routinely used to guide antimicrobial therapy of bloodstream infections; the work has implications for clinical management.