Gram-positive bacterial pathogens can evade the host innate immune response by using a cell surface protein to synthesize adenosine, a potent suppressor of inflammation, according to a new report in the Journal of Experimental Medicine.

Gram-positive pathogens such as Staphylococcus aureus use various mechanisms to display proteins on their cell surfaces, including covalent attachment to peptidoglycan by a sortase protein. Thammavongsa et al. were interested in the contribution of sortase-anchored cell surface proteins to staphylococcal immune evasion. They began by screening a transposon insertion library to identify mutations in sortase-anchored proteins that impaired the ability of S. aureus to survive in the bloodstream. One mutation that decreased survival in blood from mice, rats and humans was in sasH, which the authors renamed adenosine synthase A (adsA). The importance of AdsA for invasive staphylococcal disease was examined using a mouse renal-abscess model of S. aureus infection, and it was shown that AdsA was necessary for S. aureus replication and abscess formation in vivo.

What is the mechanism of action of AdsA? Sequence analysis revealed the presence of a 5′-nucleotidase domain, which indicated that AdsA might be able to catalyse the synthesis of adenosine from 5′-adenosine monophosphate. This activity was confirmed both in vitro and in an in vivo infection model, and was shown to be essential for S. aureus virulence in vivo. The authors went on to show that many other Gram-positive bacteria contain AdsA homologues and that Bacillus anthracis also uses adenosine synthesis as an immune evasion mechanism.

Adenosine has a variety of anti-inflammatory effects, which include inhibiting neutrophil degranulation and impairing the phagocytic activity of macrophages. This work reveals that Gram-positive pathogens use a cell surface protein to synthesize adenosine, thus downregulating the innate immune response and promoting bacterial survival within host tissues.