Abstract
ABSTRACT Staphylococcus aureus: with the sequence type (ST) 398 was previously associated with livestock carriage. However, in recent years livestock-independent S. aureus ST398 has emerged, representing a potential health risk for humans especially in nosocomial settings. Judged by whole-genome sequencing analyses, the livestock- and human originated strains belong to two different S. aureus ST398 clades but, to date, it was not known to what extent these clades differ in terms of actual virulence. Therefore, the objective of this study was to profile the exoproteomes of 30 representative S. aureus ST398 strains by mass spectrometry, to assess clade-specific differences in virulence factor secretion, and to correlate the identified proteins and their relative abundance to the strains’ actual virulence. Although the human-originated strains are more heterogeneous at the genome level, our observations show that they are more homogeneous in terms of virulence factor production than the livestock-associated strains. To assess differences in virulence, infection models based on larvae of the wax moth Galleria mellonella and the human HeLa cell line were applied. Correlation of the exoproteome data to larval killing and toxicity toward HeLa cells uncovered critical roles of the staphylococcal Sbi, SpA, SCIN and CHIPS proteins in virulence. These findings were validated by showing that sbi or spa mutant bacteria are attenuated in G. mellonella and that the purified SCIN and CHIPS proteins are toxic for HeLa cells. Altogether, we show that exoproteome profiling allows the identification of critical determinants for virulence of livestock-associated and human-originated S. aureus ST398 strains.
Highlights
Staphylococcus aureus is one of today’s major nosocomial and community-acquired pathogens
The 30 S. aureus isolates used in this study were selected from a previous collection of 182 sequence type 398 (ST398) isolates that had been derived from food, pigs, pig handlers or humans (Table 1)
In the selection of representative isolates from the different clades and sub-clades of S. aureus ST398 for our present proteome analyses, we strived to cover the majority of the identified sub-clades, as well as isolates showing the largest diversity within the different sub-clades
Summary
Staphylococcus aureus is one of today’s major nosocomial and community-acquired pathogens. Infections caused by this pathogen are associated with substantial morbidity and mortality, and S. aureus represents a major threat for public health [1]. Infections with S. aureus have become increasingly difficult to treat due to the emergence of antibiotic resistant lineages, as underpinned by methicil lin-resistant S. aureus (MRSA) [2]. MRSA was almost exclu sively identified as a hospital-acquired (HA) pathogen. Community-associated (CA) MRSA lineages were identified that caused severe infections in individuals with no apparent healthcare contacts [3]. Livestock-associated (LA) MRSA was identified in livestock and individuals exposed to livestock, especially in pig farms [4]. S. aureus with the sequence type 398 (ST398), which belongs to the clonal cluster 398 (CC398), is the most prevalent livestockassociated lineage causing zoonotic disease in Europe, North America, and Asia [5]
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