AUTHOR=Sabat Artur J. , Wouthuyzen-Bakker Marjan , Rondags Angelique , Hughes Laura , Akkerboom Viktoria , Koutsopetra Olga , Friedrich Alexander W. , Bathoorn Erik 

TITLE=Case Report: Necrotizing fasciitis caused by Staphylococcus aureus positive for a new sequence variant of exfoliative toxin E

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.964358

DOI=10.3389/fgene.2022.964358

ISSN=1664-8021

ABSTRACT=<p><bold>Objectives:</bold> Necrotizing fasciitis (NF) caused by <italic>S. aureus</italic> is a rare, aggressive and rapidly progressing superficial fascia infection with a high mortality rate. The aim of this study was to identify virulence-related genes from a complete genome sequence of a methicillin-susceptible <italic>S. aureus</italic> (MSSA) isolate recovered from a monomicrobial case of NF.</p><p><bold>Materials and methods:</bold> The MSSA isolate UMCG579 was cultured from a pus collection from the subcutis of a patient with NF. The genome of isolate UMCG579 was sequenced using MinION (Oxford Nanopore) and MiSeq (illumina) platforms.</p><p><bold>Results:</bold> The genome of the UMCG579 isolate was composed of a 2,741,379 bp chromosome and did not harbor any plasmids. Virulence factor profiling identified multiple pore-forming toxin genes in the UMCG579 chromosome, including the Panton-Valentine leukocidin (PVL) genes, and none of the superantigen genes. The UMCG579 isolate harbored a new sequence variant of the recently described <italic>ete</italic> gene encoding exfoliative toxin (type E). A search in the GenBank database revealed that the new sequence variant (<italic>ete2</italic>) was exclusively found among isolates (<italic>n</italic> = 115) belonging to MLST CC152. While the majority of <italic>S. aureus ete</italic>-positive isolates were recovered from animal sources, <italic>S. aureus ete2</italic>-positive isolates originated from human carriers and human infections. Comparative genome analysis revealed that the <italic>ete2</italic> gene was located on a 8777 bp genomic island.</p><p><bold>Conclusion:</bold> The combination of two heterogeneously distributed potent toxins, ETE2 and PVL, is likely to enhance the pathogenic ability of <italic>S. aureus</italic> isolates. Since anti-virulence therapies for the treatment of <italic>S. aureus</italic> infections continue to be explored, the understanding of specific pathogenetic mechanisms may have an important prophylactic and therapeutic value. Nevertheless, the exact contribution of ETE sequence variants to <italic>S. aureus</italic> virulence in NF infections must be determined.</p>