New mechanism for MRSA virulence discovered

Researchers at Mount Sinai, in collaboration with researchers at New York University, have published a study that sheds light on the mechanisms behind the severity, or virulence, of methicillin-resistant Staphylococcus aureus (MRSA) blood stream infections. The study, reveals that MRSA has undergone repeated mutations in the sarZ gene, a transcriptional regulator responsible for regulating virulence gene expression, leading to increased severity of blood stream infections in mouse models.

In the study, the researchers leveraged the recent introduction of USA300 into hospitals and its limited genetic variation to find mutations that contribute 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.

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 study's goal was to identify potential mechanisms by which MRSA has adapted to invasive infection environments.

Reference:

Harm van Bakel et al,MRSA lineage USA300 isolated from bloodstream infections exhibit altered virulence regulation,Cell Host & Microbe,doi 10.1016/j.chom.2022.12.003