Characterization of two novel bacteriophages infecting clinical isolates of Serratia spp. and therapeutic efficacy in a Galleria mellonella model of infection.

Abstract

AIMS: This study aimed to isolate virulent bacteriophages (phages) with the capacity to lyse clinical strains belonging to the genus Serratia. Furthermore, we aimed to characterize these phages both genomically and in terms of their potential to treat experimental Serratia infections. METHODS AND RESULTS: Virulent phages were isolated from water samples collected close to sewage outlets around Nottinghamshire, UK, using the clinical bloodstream isolate Serratia marcescens UMH9 as the host. Two phages, vB_SmaP_10b_1 (Sm10b_1) and vB_SmaS_12 (Sm12) were selected for whole genome sequencing and further characterization. Comparative genomics and proteome-based analyses identified Sm10b_1 represents a novel genus within the order Autographivirales whereas Sm12 represents a novel species belonging to a novel genus within the subfamily Queuovirinae. Host range analysis against a collection of clinical and environmental Serratia spp. (n&#xa0;=&#xa0;19) confirmed both phages produced plaques on at least 40% of the strains tested. In vivo efficacy of Sm10b_1 was determined by infecting Galleria mellonella larvae with S. marcescens UMH9 or Serratia odorifera Me113 (catheter-associated urinary tract infection isolate) followed by injection of phage Sm10b_1 (1&#xa0;&#xd7;&#xa0;107 pfu). Phage treatment significantly improved survival of larvae infected with S. marcescens (0% survival untreated vs 67% survival treated, P&#xa0;<&#xa0;0.0001) or S. odorifera (7% survival untreated vs 70% survival treated, P&#xa0;<&#xa0;0.0001). CONCLUSIONS: Sm10b_1 and Sm12 represent novel lytic phages with broad host ranges against clinical isolates of the genus Serratia. Sm10b_1 was found to be highly effective at treating experimental infections caused by S. marcescens and S. odorifera.