<i>Staphylococcus argenteus</i> and <i>Staphylococcus schweitzeri</i> are cytotoxic to human cells <i>in vitro</i> due to high expression of alpha-hemolysin Hla

Abstract

<i>Staphylococcus argenteus</i> and <i>Staphylococcus schweitzeri</i> are newly identified species of the <i>S. aureus</i>-related complex. <i>S. argenteus,</i> as occurring globally and showing significant prevalence and comparable infection and morbidity rates compared to <i>S. aureus</i>, is becoming clinically important. Whole genome sequencing has revealed the presence of several virulence genes but the molecular mechanisms of <i>S. argenteus</i> infection and virulence are largely unknown. Here, we studied the effect of a previously characterized clinical <i>S. argenteus</i> isolate on human cells <i>in vitro</i>. The clinical isolate, together with the <i>S. argenteus</i> type strain MSHR1132T and the <i>S. schweitzeri</i> type strain FSA084T, had a cytotoxic effect on the cells, which showed necrotic cell death after a few hours of treatment. The protein causing the cytotoxic effect was purified and identified by mass spectrometry as alpha-hemolysin, Hla, which is awell-known pore-forming toxin in <i>S.aureus</i>. The cytotoxic effect could be blocked with an antibody against Hla. <i>S.argenteus</i> showed 12-15 fold higher expression levels of <i>hla</i> at the RNA level and 4-6 fold higher expression levels at the protein level compared to <i>S.aureus</i>. The higher expression levels of <i>hla</i> were supported by higher RNA levels of the regulatory factors <i>sarA</i> and <i>saeR</i>. Also, the RNAIII component of the accessory gene regulator (agr) quorum sensing system was 8,000-10,000 fold higher in the <i>S.argenteus</i> isolates compared to <i>S.aureus</i>. This is the first study on the effect of <i>S.argenteus</i> on ahuman cell line and strengthens the idea of significant virulence of <i>S.argenteus</i>.