An ionophore breaks the multi-drug-resistance of Acinetobacter baumannii

Abstract

Within intensive care units, multi-drug resistant Aci-netobacter baumannii outbreaks are a frequent cause of ventilator-associated pneumonia. During the on-going COVID-19 pandemic, patients who receive venti-lator support experience a 2-fold increased risk of mor-tality when they contract a secondary A. baumannii pulmonary infection. In our recent paper (De Oliveira et al. (2022), Mbio, doi: 10.1128/mbio.03517-21), we demonstrate that the 8-hydroxquinoline ionophore, PBT2 breaks the resistance of A. baumannii to tetracy-cline class antibiotics. In vitro, the combination of PBT2 and zinc with either tetracycline, doxycycline, or tigecy-cline was shown to be bactericidal against multi-drug-resistant A. baumannii, and any resistance that did arise imposed a fitness cost. Using a murine model of pulmo-nary infection, treatment with PBT2 in combination with tetracycline or tigecycline proved efficacious against multidrug-resistant A. baumannii. These find-ings suggest that PBT2 may find utility as a resistance breaker to rescue the efficacy of tetracycline-class anti-biotics commonly employed to treat multi-drug re-sistant A. baumannii infections.

Keywords

• ionophore
• pbt2
• antimicrobial resistance
• acinetobacter baumannii
• tetracyclines