Pre-exposure to phage particles reduces their antibacterial therapeutic efficacy both in vitro and in vivo

Abstract

Objectives

phage therapy is a promising approach for infections caused by drug-resistant bacteria; this study evaluated the impact of pre-exposure to phage particles on subsequent therapy. Mice were exposed intradermally (i.d.) to Staphylococcus aureus wide-host-range phage JD007, a member of the Myoviridae family.

Methods

phage-specific antibodies were detected using ELISA. Mice were infected with S. aureus in the same way to establish a dermal abscess model, and then the efficacy of phage therapy for the mice pre-exposed to JD007 was evaluated.

Results

JD007 could induce their specific IgM and IgG. IgM levels peaked on the 7th day following exposure, and IgG levels peaked on the 30th day after final immunization. Neutralization assays demonstrated that specific antibodies could reduce JD007’s infectivity to S. aureus in vitro. Furthermore, mice previously exposed to JD007 three times showed decreased phage therapeutic efficacies, leading to delayed recovery and even exacerbating abscesses. White blood cells and lymphocytes also increased. Despite pre-exposing the mice to JD007 once, the abscess areas following phage treatment did not differ from those of the infection group with naive mice. The western blot results showed that anti-phage antibodies could recognize the predicted major capsid protein and phage tail protein.

Conclusions

pre-exposure to phage particles may induce phage-neutralization antibodies and inhibit their therapeutic efficacies, delaying recovery or even exacerbating S. aureus-associated dermal abscesses for later treatment.