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Why look inside cells? Although S. aureus is mainly extracellular, it can persist within monocytes and macrophages. We found that internalization markedly increased antibiotic survival, making the intracellular niche a potential reservoir for treatment failure.

4/8/26, 10:03 am0 reposts0 likes

To find the genes behind this lifestyle, we built a genome-wide CRISPRi-seq screen targeting 2,865 S. aureus genes in a THP-1 co-infection model, then compared intracellular and extracellular fitness. @veeninglab.com @vincentdebakker.bsky.social

The intracellular and extracellular fitness landscapes separated clearly. The screen recovered known virulence factors and uncovered new genes specifically needed inside phagocytes. Among them: mnhB, part of the Mnh1 cation–proton antiporter.

Knocking down mnhB reduced early phagocytic uptake and intracellular bacterial burden. Importantly, the phenotype held across three distinct S. aureus lineages. Excitingly, when mnhB was depleted, levofloxacin cleared intracellular bacteria more effectively.