Nature Medicine study describes results showing that PSM-alpha efficiently kills white blood cells.
Newly described proteins in drug-resistant strains of the Staphylococcus aureus bacterium attract and then destroy protective human white blood cells, according to scientists at the NIAID.
The group discoverd phenol-soluble modulins (PSMs) secreted by S. aureus and identified the genes that encode those PSM proteins. They then compared PSM production between community-associated (CA) MRSA and the most prominent hospital-associated MRSA strains.
The NIAID team found PSM genes in all MRSA strains. Production of the proteins, however, was higher in CA-MRSA strains known for severe virulence.
To determine whether PSMs contribute to virulence, the scientists developed test strains using the most widespread isolates of CA-MRSA, called USA300 and USA400. Each test strain had a certain combination of PSM-encoding genes removed so the researchers could ascertain whether those genes affected virulence. They then observed how laboratory mice responded to the test strains.
The researchers say that they pinpointed the psm-alpha gene cluster, which makes PSM-alpha protein, as playing an essential role in determining CA-MRSA virulence and ultimately disease severity.
To understand how PSMs contribute to virulence, the investigators then examined the role of the molecules in S. aureus evasion of human immune defenses. They observed that the PSM-alpha genes generated the most resistance activity and the PSM-alpha proteins were best at destroying most immune cells that help protect against infection and disease. In all instances, the scientists found that PSM-alpha molecules caused the greatest destruction of white blood cells, an effect that occurred rapidly.
The research was done by scientists at University of Tübingen and University of Washington. The study is published online in Nature Medicine.