Human urine alters methicillin-resistant Staphylococcus aureus virulence and transcriptome

AbstractGram-positive methicillin-resistant Staphylococcus aureus (MRSA) is an emerging cause of hospital-associated urinary tract infections, especially in catheterized individuals. Despite being rare, MRSA-UTI are prone to potentially life-threatening exacerbations such as bacteremia that can be refractory to routine antibiotic therapy. Hence, MRSA-UTI is an important of research topic. To delineate molecular mechanisms governing MRSA urinary pathogenesis, we exposed three S. aureus strains, of which two were MRSA, to human urine and analyzed virulence characteristics and gene expression. We also analyzed MRSA-1369 transcriptome following cultivation in human urine for 2h. Our results reveal that human urine induces global changes in MRSA transcriptome, marked by changes in genes encoding proteins involved in metabolic pathways, virulence, and transcriptional regulators. In addition, in vitro assays also showed that human urine alters, in a strain-specific manner, adherence to human bladder epithelial cells and fibronectin, hemolysis of sheep RBCs, and surface hydrophobicity. In summary, our results provide first important insights into how the urine may specifically alter MRSA physiology in turn facilitating MRSA survival in the nutrient-limiting and hostile urinary microenvironment.ImportanceMethicillin-resistant Staphylococcus aureus (MRSA) is an uncommon cause of urinary tract infections (UTI) in the general population. However, it is important to understand MRSA pathophysiology in the urinary tract because isolation of MRSA in urine samples is often secondary to potentially life-threatening MRSA bacteremia. In this report, we describe that cultivation in human urine alters MRSA global gene expression and virulence. We hypothesize that these alterations may aid MRSA adapt to the nutrient-limiting, immunologically hostile conditions within the urinary tract.