Staphylococcus aureus stifles its host's immune response by producing an immunosuppressive molecule, report Thammavongsa and colleagues.

The new study reveals that without the cell wall enzyme adenosine synthase A (AdsA), most staphylococci fail to thrive and cause severe disease in mice. The gene encoding AdsA contains a 5′-nucleotidase domain, making it similar to a family of mammalian enzymes that convert adenosine monophosphate into adenosine. Adenosine has many immune-dampening effects including blunting T cell proliferation, inhibiting cytokine production, and blocking neutrophil degranulation and superoxide production. Bacterial isolates expressing AdsA were previously associated with invasive disease in humans, but the connection between AdsA and pathogenesis wasn't understood.

Now it appears that at least two strains of staph (including one methicillin-resistant strain) and the anthrax pathogen Bacillus anthracis use AdsA to tap into the adenosine system. Bacteria with intact adsA survived longer in whole blood from rodents and humans than did adsA-deficient bacteria. And mice infected with adsA-deficient strains cleared infection quickly and rarely developed the abscesses characteristic of progressive staph infections. The virulence of adsA-deficient staph could be regained by genetically restoring the enzyme. With AdsA around, adenosine levels were higher, presumably allowing staph to escape destruction by neutrophils.

Manipulating the adenosine pathway may turn out to be a widespread phenomenon, as the authors also identified putative 5′-nucleotidase–encoding genes in a variety of gram-positive bacteria.