Isolation and Characterization of a Novel Phage SaGU1 that Infects Staphylococcus aureus Clinical Isolates from Patients with Atopic Dermatitis

Yuzuki Shimamori,Tomoko Kubori,Hiroki Ando,Tomoe Kitao,Ajeng K. Pramono,Shigeki Takeda,Tohru Suzuki,Hiroki Nagai,Shin-ichi Aizawa

doi:10.1007/s00284-021-02395-y

Abstract

The bacterium Staphylococcus aureus, which colonizes healthy human skin, may cause diseases, such as atopic dermatitis (AD). Treatment for such AD cases involves antibiotic use; however, alternate treatments are preferred owing to the development of antimicrobial resistance. This study aimed to characterize the novel bacteriophage SaGU1 as a potential agent for phage therapy to treat S. aureus infections. SaGU1 that infects S. aureus strains previously isolated from the skin of patients with AD was screened from sewage samples in Gifu, Japan. Its genome was sequenced and analyzed using bioinformatics tools, and the morphology, lytic activity, stability, and host range of the phage were determined. The SaGU1 genome was 140,909 bp with an average GC content of 30.2%. The viral chromosome contained 225 putative protein-coding genes and four tRNA genes, carrying neither toxic nor antibiotic resistance genes. Electron microscopy analysis revealed that SaGU1 belongs to the Myoviridae family. Stability tests showed that SaGU1 was heat-stable under physiological and acidic conditions. Host range testing revealed that SaGU1 can infect a broad range of S. aureus clinical isolates present on the skin of AD patients, whereas it did not kill strains of Staphylococcus epidermidis, which are symbiotic resident bacteria on human skin. Hence, our data suggest that SaGU1 is a potential candidate for developing a phage therapy to treat AD caused by pathogenic S. aureus.

Highlights

Staphylococcus aureus is a Gram-positive commensal bacterium present in human microbiota, it can act as an opportunistic pathogen causing several infectious diseases, including pneumonia, endocarditis, bacteremia [1,2,3,4], and atopic dermatitis (AD), which is a common inflammatory skin disease that can be caused by abnormal colonization of S. aureus [5, 6]
Two hundred microliters of stationary phase culture of the host bacteria was mixed with 0.6% soft agar and layered on the lysogeny broth (LB) plate
Considering that stable phages are required for phage therapy [55], we examined whether SaGU1 is stable at various temperatures and pH values

Summary

Introduction

Staphylococcus aureus is a Gram-positive commensal bacterium present in human microbiota, it can act as an opportunistic pathogen causing several infectious diseases, including pneumonia, endocarditis, bacteremia [1,2,3,4], and atopic dermatitis (AD), which is a common inflammatory skin disease that can be caused by abnormal colonization of S. aureus [5, 6].The current treatment for such AD cases includes the use of topical antibiotics; the resultant symptomatic improvement is temporary, often resulting in the development of antibiotic resistance [7]. Staphylococcus aureus is a Gram-positive commensal bacterium present in human microbiota, it can act as an opportunistic pathogen causing several infectious diseases, including pneumonia, endocarditis, bacteremia [1,2,3,4], and atopic dermatitis (AD), which is a common inflammatory skin disease that can be caused by abnormal colonization of S. aureus [5, 6]. A previous study in the USA, reported that 80% of patients with AD showed colonization of S. aureus on the skin, 16% of which were identified as MRSA [9]. Another issue associated with antibiotic treatment of AD treatment is the impact on the commensal bacterial community [10, 11].

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Results