Isolation, partial characterization, therapeutic, and safety evaluation of carbapenem-resistant Acinetobacter baumannii lytic phage in a mouse model

Abstract

Abstract Background Antimicrobial resistance (AMR) is a major worldwide health concern, characterized by the ability of microorganisms to withstand the effects of medications that once effectively treated infections. Phage therapy has emerged as a promising alternative for management of multidrug-resistant (MDR) bacterial infections. Acinetobacter baumannii (A. baumannii) exemplifies the emergence of bacteria resistant to clinically relevant antimicrobials, leading to severe nosocomial infections and exhibiting extensive and pan drug-resistant (XDR and PDR) traits. In response, this study isolated A. baumannii virulent phage designated as vB_AbaP_PhE54 against carbapenem-resistant A. baumannii (CRAB) pathogen and examined its morphological characteristics using an electron micrograph. Phage stability at different temperatures, pH, chloroform, safety, therapeutic evaluation, and growth kinetics have been analyzed. Results The A. baumannii phage vB_AbaP_PhE54 belongs morphologically to the Podoviridae family with very short, noncontractile tails, the phage demonstrated high thermal tolerance and infectivity across a pH range of 4–11, although it displayed a narrow host range. One-step growth kinetics indicated a burst size of 85 PFU (Plaque Forming Unit) per infected cell and a latent period of 20 min. Additionally, therapeutic efficiency in a mouse model showed total elimination of CRAB pathogen from lungs homogenates of mice and recovery from lung inflammation in all infected mice. On the other hand, safety evaluation of isolated phage revealed no adverse effects on structural or morphological tissue integrity. Conclusions These findings suggest that A. baumannii phage vB_AbaP_PhE54 could be a viable safe therapeutic option against A. baumannii infections, warranting further research into its clinical applications.

Keywords

• Acinetobacter baumannii
• CRAB
• Antimicrobial resistance
• Antibiotics
• Phage therapy
• Podoviridae