A Novel Bacteriophage Genus Infects Carbapenem Resistant Acinetobacter Baumannii Via a Non-Capsular Receptor and Provides Protection in Vivo

Abstract

Extensive drug resistance (XDR) in Acinetobacter baumannii and other pathogens has revitalized bacteriophage as a therapeutic consideration. Six phages (AB1I1L, AB1I1M, AB1I1P, AB1I1T, AB2I2, AB2I3) targeting A. baumannii were isolated from wastewater. These represent a newly described phage genus with rapid adsorption and potent lysis. 18/40 A. baumannii clinical isolates, including 11/27 carbapenem-resistant isolates, were susceptible to one of the isolated phages. Importantly, in vitro­-derived, phage resistant bacteria were killed in human ascites, demonstrating decreased biofitness. In contrast to most described phages that target A. baumannii, bacterial capsule is not the primary receptor. Capsule impedes phage activity in vitro. 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 in vitro conditions. These phages are potential candidates for phage therapy, warranting additional preclinical evaluation as adjunctive treatment for A. baumannii infections.

Note:
Funding Information: This study was supported, in part, by the Dr. Louis Sklarow Memorial Trust to OGG. This work was also supported by the Department of Veterans Affairs VA Merit Review (I01 BX004677-01) (TAR). This study was also partially funded by the U.S. Defense Health Program (DHP) Operations and Maintenance.

Declaration of Interests: The authors declare that they have no competing interests.

Ethics Approval Statement: Animal studies were reviewed and approved by the Veterans Administration and the University at Buffalo-SUNY Institutional Animal Care Committees and were carried out in strict accordance with the recommendations in the guidelines delineated in the "NIH Guide for the Care and Use of Laboratory Animals" (revised 1985) and the "Ethics of Animal Experimentation Statement" (Canadian Council on Animal Care, July 1980) as monitored by the Institutional Animal Care and Use Committee (IACUC). All efforts were made to minimize suffering. Veterinary care for the animals was supplied by the staff of the Veterans Administration Animal Facility under the direction of a fully licensed veterinarian.