Safety Evaluation of Staphylococcus aureus Bacteriophage Based on Transcriptome

doi:10.13560/j.cnki.biotech.bull.1985.2019-0696

Abstract

Abstract: The emergence of multidrug-resistant bacteria has forced us to consider bacteriophage therapy as one of the possible alternative therapies. The aim of this study is to investigate the safety and long-term use condition of Staphylococcus aureus bacteriophage in mammary perfusion therapy in mice by transcriptional sequencing. Twenty-four Kunming female mice lactating for 10 d were randomly divided into three groups,including healthy control group（T01）,bacteriophage VBSM-A1 perfusion group（T02）and bacteriophage cocktail perfusion group（T03）. S. aureus phage suspension of different components was injected into the fourth pair of mammary glands（abdomen）of mice by non-invasive method,and then the mice and the changes of histopathology and TNF-α in the breast tissue were observed. Meanwhile,transcriptome sequencing was used to analyze the mammary gland of mice. The results showed that phage infusion caused slight inflammation in the mammary glands of mice,but did not cause physiological state changes of the mice. At the same time,the number of phages decreased significantly（started：5×10⁷ PFU/gland;24 h latter：10^3.6 and 10^4.4 PFU/gland respectively）during 24 h,suggesting that the way and dosage of phage administration needed further exploration. The prospect of combined application of phages and antibiotics to reduce the phage immune response and antibiotic resistance is proposed,which provides a theoretical and experimental basis for the use of subsequent phages at the transcriptome level.

Key words: transcriptome sequencing, bacteriophage therapy, phage safety, mouse

GENG Hui-jun, ZOU Wei, CUI Hui-jing, LI Xiao-yu, WANG Li-li, XU Yong-ping. Safety Evaluation of Staphylococcus aureus Bacteriophage Based on Transcriptome[J]. Biotechnology Bulletin, 2019, 35(12): 64-75.

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