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A Mouse Model to Assess Innate Immune Response to Staphylococcus aureus Infection
Published on: February 28, 2019
Immunotherapy Targeting Adenosine Synthase A Decreases Severity of Staphylococcus aureus Infection in Mouse Model
Bao-Zhong Zhang1,2,3, JianPiao Cai2, Bin Yu1,4
1School of Biomedical Sciences.
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.
Insights
This study identifies adenosine synthase A (AdsA) as a promising target for Staphylococcusaureus vaccines. Antibodies against AdsA protected mice against S. aureus infections, suggesting AdsA-based immunotherapies could combat drug-resistant strains.
Area of Science:
- Microbiology
- Immunology
- Vaccine Development
Background:
- Staphylococcus aureus is a significant pathogen, with methicillin-resistant S. aureus (MRSA) posing a major public health threat due to antibiotic resistance.
- The emergence of antibiotic-resistant bacteria necessitates alternative treatments, including immunotherapy.
- S. aureus utilizes adenosine to evade the host immune system, highlighting potential therapeutic targets.
Purpose of the Study:
- To investigate adenosine synthase A (AdsA), a cell wall-anchored enzyme in S. aureus, as a potential target for immunotherapy.
- To evaluate the efficacy of a vaccine targeting AdsA in preclinical models.
Main Methods:
- Mice were vaccinated with aluminum hydroxide-formulated recombinant AdsA (rAdsA).
- Immune response was assessed by measuring anti-AdsA antibody titers.
- Vaccine efficacy was tested in three mouse infection models using two S. aureus strains.
- Passive transfer experiments and assessment of immune cell-mediated killing were performed.
Main Results:
- Vaccination with rAdsA successfully induced high-titer anti-AdsA antibodies in mice.
- The induced antibodies provided consistent protection against S. aureus challenge in multiple infection models.
- Passive transfer of anti-AdsA antibodies conferred protection, confirming their role in defense.
- AdsA-specific antisera enhanced the killing of S. aureus by immune cells.
Conclusions:
- AdsA is a viable and promising target for vaccine and therapeutic development against S. aureus infections.
- AdsA-based immunotherapies hold potential for combating severe S. aureus diseases, including those caused by MRSA.
- Targeting AdsA offers a novel strategy to overcome antibiotic resistance in S. aureus.

