A bacteriophage genus infects carbapenem resistant Acinetobacter baumannii via a non-capsular receptor and provides protection in vivo

Extensive drug resistance (XDR) in <i>Acinetobacter baumannii</i> and other pathogens has revitalized bacteriophage as a therapeutic consideration. Six phages (AB1I1L, AB1I1M, AB1I1P, AB1I1T, AB2I2, and AB2I3) targeting <i>A. baumannii</i> were isolated from wastewater. These represent a previously undescribed phage genus with rapid adsorption and potent lysis. 18/40 <i>A. baumannii</i> clinical isolates, including 11/27 carbapenem-resistant isolates, were susceptible to one of the isolated phages. Importantly, <i>in vitro</i>-derived, phage resistant bacteria were killed in human ascites, demonstrating decreased biofitness. In contrast to most described phages that target <i>A. baumannii</i>, the bacterial capsule is not the primary receptor. Capsule impedes phage activity <i>in vitro</i>. The treatment of an XDR isolate using phage monotherapy in a rat subcutaneous abscess model showed dose-dependent efficacy, though a higher sustained concentration of phage was needed when compared with <i>in vitro</i> conditions. These phages are potential candidates for phage therapy, warranting additional preclinical evaluation as adjunctive treatment for <i>A. baumannii</i> infections.