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ABSTRACT: Sequencing Human and Canine Bacteremia Staphylococcus pseudintermedius isolates

PROVIDER: PRJNA521119 | ENA |

REPOSITORIES: ENA

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			Action	DRS
		Other
	SRR8538950_1.fastq.gz	Fastqsanger.gz
	SRR8538960_1.fastq.gz	Fastqsanger.gz
	SRR8538951_1.fastq.gz	Fastqsanger.gz
	SRR8538951_2.fastq.gz	Fastqsanger.gz

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Staphylococcus pseudintermedius

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

Project description: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.

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Project description:Staphylococcus aureus is the most common cause of hospital-acquired infection. In healthy hosts outside of the health care setting, S.aureus is a frequent colonizer of the human nose but rarely causes severe invasive infection such as bacteremia, endocarditis, or osteomyelitis. To identify genes associated with community-acquired invasive isolates, regions of genomic variability, and the S.aureus population structure, we compared 61 community-acquired invasive isolates of S.aureus and 100 nasal carriage isolates from healthy donors using a microarray spotted with PCR products representing every gene from the seven S.aureus sequencing projects. The core genes common to all strains were identified, and 10 dominant lineages of S.aureus were clearly discriminated. Each lineage carried a unique combination of hundreds of core variable (CV) genes scattered throughout the chromosome, suggesting a common ancestor but early evolutionary divergence. Many CV genes are regulators of virulence genes or known or predicted to be expressed on the bacterial surface and to interact with the host during nasal colonization and infection. Within each lineage, isolates showed substantial variation in the carriage of mobile genetic elements and their associated virulence and resistance genes, indicating frequent horizontal transfer. However, we were unable to identify any association between lineage or gene and invasive isolates. We suggest that the S.aureus gene combinations necessary for invasive disease may also be necessary for nasal colonization and that community-acquired invasive disease is strongly dependent on host factors. Data is also available from http://bugs.sgul.ac.uk/E-BUGS-33

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