Researchers at Mount Sinai, in collaboration with researchers at New York University, published a study in host cell and microbe Which sheds light on the mechanisms underlying the severity or virulence of methicillin-resistant Staphylococcus aureus (MRSA) infection. The study, published in January 2023, revealed that MRSA has frequent mutations in the sarZ gene, a transcriptional regulator responsible for regulating virulence gene expression, leading to increased severity of bloodstream infections in murine models.
The widespread MRSA USA300 lineage has recently become a leading cause of hospital-associated bloodstream infections (BSIs). In the study, the researchers took advantage of the recent introduction of USA300 into hospitals and its limited genetic diversity to find mutations that contribute to its success in a new environment. The authors found that USA300 infection shows variable regulation of virulence. Using comparative genomics, they found the genes involved in this phenotype and discovered frequent, independent mutations in the sarZ transcriptional regulator. These mutations increased the 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 has been shown to be critical in the pathogenesis of USA300 BSI isolates.
MRSA is endemic throughout the United States and causes a wide range of diseases, including invasive bloodstream infections associated with a high mortality rate. The aim of the study was to identify potential mechanisms by which MRSA has adapted to environments of invasive infection.
“The results of our study provide a better understanding of the factors that contribute to the virulence of MRSA and may ultimately help uncover new therapeutic approaches,” said Herm van Baeckel, PhD, professor of genetics and genomics at the Icahn School of Medicine at Mount Sinai. One of the study’s authors. “The continued evolution of MRSA has changed the ways in which it regulates its virulence in bloodstream infections. Our work highlights the ongoing evolution of the major MRSA strain and suggests that USA300 strains can improve their fitness by modulating virulence regulation.”
The study focused on the USA300 lineage of MRSA, and future work will investigate additional strains as well as adaptations in methicillin-susceptible Staphylococcus aureus (MSSA) infections.
Mount Sinai Health System