Dataset Information

Staphylococcus aureus isolates from the gut and the blood are ‘separated’ by host barrier integrity

ABSTRACT: The opportunistic pathogen Staphylococcus aureus is carried asymptomatically by about one-third of the human population. Body sites known to be colonized by S. aureus are the skin, nasopharynx and gut. In particular, the mechanisms that allow S. aureus to pass the gut epithelial barrier and to invade the bloodstream are poorly understood. Therefore, our present study was aimed at investigating possible differences between gut-colonizing and bacteremia isolates of S. aureus. To this end, 74 gut-colonizing isolates from healthy individuals and 144 blood-culture isolates were characterized by whole-genome sequencing. Subsequently, the cellular and extracellular proteomes of six representative isolates were examined by mass spectrometry. Lastly, the virulence potential of these isolates was evaluated using infection models based on human gut epithelial cells, blood cells, and a small animal infection model. Intriguingly, our results show that gut-colonizing and bacteremia isolates with the same sequence type (ST1 or ST5) are very similar at the genomic and proteomic levels. Nonetheless, they display differences in virulence, but gut-colonizing isolates may be more virulent than bacteremia isolates and vice versa. Importantly, we show that the main decisive factor preventing infection of gut epithelial cells in vitro is the presence of a tight barrier. Based on our present observations, we propose that the integrity of the gut epithelial layer, rather than the pathogenic potential of a gut-colonizing S. aureus strain, is the main decisive factor that determines whether this colonizer will become an invasive pathogen.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Staphylococcus Aureus

SUBMITTER: Sandra Maass

LAB HEAD: Dörte Becher

PROVIDER: PXD030971 | Pride | 2023-03-11

REPOSITORIES: Pride

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			Action	DRS
	201217_O2_P2_SK_Raineri_cell_1_1.raw	Raw
	201217_O2_P2_SK_Raineri_cell_1_10.raw	Raw
	201217_O2_P2_SK_Raineri_cell_1_2.raw	Raw
	201217_O2_P2_SK_Raineri_cell_1_3.raw	Raw
	201217_O2_P2_SK_Raineri_cell_1_4.raw	Raw

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Publications

Staphylococcus aureus populations from the gut and the blood are not distinguished by virulence traits-a critical role of host barrier integrity.

Raineri Elisa J M EJM Maaß Sandra S Wang Min M Brushett Siobhan S Palma Medina Laura M LM Sampol Escandell Neus N Altulea Dania D Raangs Erwin E de Jong Anne A Vera Murguia Elias E Feil Edward J EJ Friedrich Alex W AW Buist Girbe G Becher Dörte D García-Cobos Silvia S Couto Natacha N van Dijl Jan Maarten JM

Microbiome 20221226 1

<h4>Background</h4>The opportunistic pathogen Staphylococcus aureus is an asymptomatically carried member of the microbiome of about one third of the human population at any given point in time. Body sites known to harbor S. aureus are the skin, nasopharynx, and gut. In particular, the mechanisms allowing S. aureus to pass the gut epithelial barrier and to invade the bloodstream were so far poorly understood. Therefore, the objective of our present study was to investigate the extent to which ge ...[more]

PMID: 36567349

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Project description:Livestock-associated (LA) methicillin-resistant Staphylococcus aureus (MRSA) and strains of sequence type 398 (ST398), which first became known for its widespread colonization of pigs but are now also rapidly emerging in the number of human colonization and infections. The ability of broad host adaption in combination with a consciously evolves by acquisition of virulence gene or mobile genetic elements (MGE) have been increasingly addressed ST398 lineage a serious threat to public health. The present study was aimed to track out how the diverse ST398 lineage, which colonized or infected in a broad range of reservoirs and various geographic regions, is actually reflected in the course of virulence evolution. We therefore profiled the extracellular proteome, representing the main reservoir of virulence factors, of 30 representative clinical isolates using label-free quantitative mass spectrometry. The results show that these isolates can be divided into five distinct clusters based on their exoproteome identities and abundance signatures. The majority of proteins identified were predicted as cytoplasmic proteins showing substantial heterogeneity among our 30 investigated isolates. Only 50% of isolates their exoproteome clustering of isolates can be correlated the clustering based on genome sequences suggested that the large-scale extend of genotype changes over time. To assess the virulence and cytotoxicity of the 30 investigated isolates, we employed infection models based on Galleria mellonella and HeLa cells. The results uncovered the grouping of clinical isolates based on their virulence or cytotoxicity have apparently distinctive exoproteome signatures and particular exoproteins could play decisive roles in pathogenicity of this specific S. aureus lineage. Altogether, the combination of exoproteome and virulence analysis contribute to the comprehensive insights for the impact of genome diversity on the global production of virulence factors of this zoonotic lineage, and more importantly, our outcomes as well as our approach provided an effective pipeline to define proteomic signatures of S. aureus virulence.