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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / biosynthesis
  • Animals
  • Anti-Bacterial Agents / therapeutic use
  • Antibodies, Bacterial / pharmacology*
  • Bacterial Proteins / immunology*
  • Disease Models, Animal
  • Female
  • Immunization, Passive*
  • Immunotherapy
  • Ligases / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Rabbits
  • Staphylococcal Skin Infections / therapy*
  • Staphylococcus aureus / enzymology

Substances

  • Anti-Bacterial Agents
  • Antibodies, Bacterial
  • Bacterial Proteins
  • Ligases
  • Adenosine