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J Infect Dis. 2017 Jul 15;216(2):245-253. doi: 10.1093/infdis/jix290.

Immunotherapy Targeting Adenosine Synthase A Decreases Severity of Staphylococcus aureus Infection in Mouse Model.

Zhang BZ1,2,3, Cai J2, Yu B1,4, Xiong L2, Lin Q1,5, Yang XY1, Xu C1,5, Zheng S1, Kao RY2, Sze K2, Yuen KY2,4, Huang JD1,3,5.

Author information

1
School of Biomedical Sciences.
2
Department of Microbiology.
3
HKU-Shenzhen Institute of Research and Innovation.
4
State Key Laboratory of Emerging Infectious Diseases, University of Hong Kong.
5
Centre for Synthetic Biology Engineering Research; Shenzhen Institutes of Advanced Technology, Guangdong, China.

Abstract

Staphylococcusaureus is a severe pathogen found in the community and in hospitals. Most notably, methicillin-resistant S. aureus (MRSA) is resistant to almost all antibiotics, which is a growing public health concern. The emergence of drug-resistant strains has prompted the search for alternative treatments such as immunotherapeutic approaches. Previous research showed that S. aureus exploit the immunomodulatory attributes of adenosine to escape host immunity. In this study, we investigated adenosine synthase A (AdsA), an S. aureus cell wall-anchored enzyme as possible targets for immunotherapy. Mice vaccinated with aluminum hydroxide-formulated recombinant AdsA (rAdsA) induced high-titer anti-AdsA antibodies, thereby providing consistent protection in 3 mouse infection models when challenged with 2 S. aureus strains. The importance of anti-AdsA antibody in protection was demonstrated by passive transfer experiments. Moreover, AdsA-specific antisera promote killing S. aureus by immune cells. Altogether, our data demonstrate that the AdsA is a promising target for vaccines and therapeutics development to alleviate severe S. aureus diseases.

KEYWORDS:

AdsA; S. aureus; adenosine synthase A; immunotherapy

PMID:
28633319
PMCID:
PMC5853884
DOI:
10.1093/infdis/jix290
[Indexed for MEDLINE]
Free PMC Article

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