Novel Mechanism for MRSA Virulence Identified

Researchers have discovered the mechanisms behind the severity, or virulence, of methicillin-resistant Staphylococcus aureus (MRSA) blood stream infections. The widespread community-associated MRSA USA300 lineage has recently become a leading cause of hospital-associated bloodstream infections (BSIs). In the study, the researchers leveraged the recent introduction of USA300 into hospitals and its limited genetic variation to find mutations that contributed to its success in a new environment.

The researchers found that USA300 infections exhibit altered virulence regulation. Using comparative genomics, they found the genes involved in this phenotype and discovered repeated and independent mutations in the transcriptional regulator sarZ. These mutations resulted in increased virulence of USA300 BSI isolates in a mouse model of BSI. The sarZ mutations resulted in increased expression and production of the surface protein ClfB, which was shown to be critical for the pathogenesis of USA300 BSI isolates.

What is MRSA

MRSA is endemic across the United States and causes a wide range of diseases, including invasive bloodstream infections that are associated with high mortality. The purpose of the research was to identify potential mechanisms by which MRSA has adapted to invasive infection environments.

"The findings of our study provide a better understanding of the factors contributing to MRSA virulence and may ultimately help uncover new treatment approaches," said Harm van Bakel, PhD, Professor of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai and one of the corresponding authors of the study. "The continued evolution of MRSA has changed the ways it regulates its virulence in bloodstream infections.” “Our work highlights the ongoing evolution of a major MRSA lineage and suggests that USA300 strains can optimize their fitness through altered regulation of virulence."

Source-Eurekalert