Abstract
As an alternative approach against multidrug-resistant bacterial infections, phages are now being increasingly investigated as effective therapeutic agents. Here, aiming to design an efficient phage cocktail against Aeromonas salmonicida infections, we isolated and characterized five lytic A. salmonicida phages, AS-szw, AS-yj, AS-zj, AS-sw, and AS-gz. The results of morphological and genomic analysis suggested that all these phages are affiliated to the T4virus genus of the Caudovirales order. Their heterogeneous lytic capacities against A. salmonicida strains were demonstrated by experiments. A series of phage cocktails were prepared and investigated in vitro. We observed that the cocktail combining AS-gz and AS-yj showed significantly higher antimicrobial activity than other cocktails and individual phages. Given the divergent genomes between the phages AS-yj and AS-gz, our results highlight that the heterogeneous mechanisms that phages use to infect their hosts likely lead to phage synergy in killing the host. Conclusively, our study described a strategy to develop an effective and promising phage cocktail as a therapeutic agent to combat A. salmonicida infections, and thereby to control the outbreak of relevant fish diseases. Our study suggests that in vitro investigations into phages are prerequisite to obtain satisfying phage cocktails prior to application in practice.
Highlights
Aeromonas salmonicida is a waterborne pathogenic bacterium considered to be one of the most relevant fish pathogens and is the causative agent of furunculosis in aquaculture systems worldwide (Janda and Abbott, 2010; Austin and Austin, 2016; Menanteau-Ledouble et al, 2016)
We evaluated the stability of the phages and the phage cocktails efficiency when facing various environmental factors including pH and temperature according to the methods described by Li et al (2016)
Our results demonstrate that the phages we isolated have high ability in infecting various A. salmonicida subspecies, suggesting promising in applications to treat the infections caused by A. salmonicida pathogens
Summary
Aeromonas salmonicida is a waterborne pathogenic bacterium considered to be one of the most relevant fish pathogens and is the causative agent of furunculosis in aquaculture systems worldwide (Janda and Abbott, 2010; Austin and Austin, 2016; Menanteau-Ledouble et al, 2016). The intensive use of antibiotics in treating furunculosis has driven the attendant development of multidrug-resistance in A. salmonicida (Cabello, 2006; Defoirdt et al, 2007; Reith et al, 2008; Kim et al, 2011; Austin and Austin, 2016) and has become a global concern (Tanji et al, 2005; Barbu et al, 2016). The host range of a single phage type tends to be relatively narrow, often consisting of only a subset of strains of a given bacterial species. This extreme specificity severely limits the use of only one phage type to control bacterial infections. Using only a single phage type to control a bacterial infection can readily drive the emergence of phage-resistant bacterial mutants (Hyman and Abedon, 2010; Pirnay et al, 2011; Chan et al, 2013; Castillo et al, 2015; Melo et al, 2016; Yen et al, 2017)
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