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

Abstract

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

Pathogenesis of Staphylococcus haemolyticus on primary human skin fibroblast cells

“…In contrast to our results, Johansson, Rautelin [ 49 ] demonstrated that S. aureus isolates were not cytotoxic to HeLaor HT29 cells. Also, El-Housseiny, Aboulwafa [ 50 ] showed that the cell-free supernatants of the four E. coli isolates caused nearly no cytotoxicity after 3 h of Vero cell infection.…”

A Novel Surface-Exposed Polypeptide Is Successfully Employed as a Target for Developing a Prototype One-Step Immunochromatographic Strip for Specific and Sensitive Direct Detection of Staphylococcus aureus Causing Neonatal Sepsis

“…Checking the sequence specificity of the first 300 aa of NWMN_1649 (BAF67921.1) of S. aureus indicated that the region between aa 46 to 157 looked distinct from the closest match ( Figure 1 a). Performing a BlastP search using the selected polypeptide against genus Staphylococcus while excluding S. aureus returned few hits from staphylococcal species not known to cause major human infections, if any, such as S. schweitzeri, S. argenteus, and S. sciuri ( Figure 1 b) [ 36 , 37 ]. Multiple sequence alignment using Clustal Omega of the selected peptide and its closest matches from the BlastP analysis ( Figure 1 c), and phylogenetic tree analysis ( Figure S1 ) confirmed that the S. aureus NWMN_1649 (BAF67921.1) 112 aa (46–157) peptide is distinct from its closest matches from other species.…”

The Human Microbiota and Skin Cancer

“…When these data were further analyzed with DESeq2, S. argenteus was found to be more abundant in CTCL lesions than in normal-appearing healthy skin [61]. As S. argenteus can induce a 4-to 6-fold increase in the level of alpha-hemolysin exotoxin compared to S. aureus [62], the authors have suggested the possible pathogenic role of S. argenteus in CTCL. Further large-scale studies are needed to determine whether these bacteria are associated with the pathogenesis or the clinical course of CTCL.…”