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Resistance mechanism schema for high-level cefiderocol resistance. In a NDM-producing CRKP, while CirA functioning normally, plenty of cefiderocol molecules have access to periplasmic space, and thus NDM is insufficient to hydrolyze cefiderocol (left). While the CirA was inactivated (right), the important gateway for cefiderocol entry is switched off. Periplasmic drug concentration then dramatically decreases, making NDM sufficient to hydrolyze cefiderocol.
