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Staphylococcus aureus

ABSTRACT: Metatranscriptomic analysis of prosthetic joint infection Staphylococcus aureus

PROVIDER: PRJNA700676 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14571306_1.fastq.gz	Fastqsanger.gz
	SRR14571306_2.fastq.gz	Fastqsanger.gz
	SRR14571307_1.fastq.gz	Fastqsanger.gz
	SRR14571307_2.fastq.gz	Fastqsanger.gz
	SRR14571308_1.fastq.gz	Fastqsanger.gz

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In situ Staphylococcus aureus gene expression in a human prosthetic joint infection

Project description:Little is known about regulation of gene activity of the major pathogen Staphylococcus aureus during actual human infection. Here we characterize the transcriptome using deep RNA sequencing and the metabolome using NMR of S. aureus infected joint fluid derived from an acute human prosthetic joint infection, and compare them with the genome, transcriptome and metabolome of an isolate obtained from the sample grown in vitro (LB medium). The transcriptome indicated that the bacterial infection sustained on a versatile human-cell-based diet consisting of amino acids, glycans and nucleosides, since significant upregulation of genes involved in the catabolic degradation pathways of these compounds were observed in situ. This is consistent with metabolite analysis of the infected joint fluid and of S. aureus culture supernatants where the concentration of most amino acids and some amino sugars were found to be higher in the joint fluid, whereas the concentration of glucose was higher in culture supernatant. Furthermore, presumably because of oxygen limitations in the joint fluid, transcriptomic evidence for fermentation was observed, consistent with the presence of fermentation products (ethanol) in situ. Moreover, many, but not all, of the known virulence factor genes were upregulated in situ as well as the nine genes encoding the iron uptaking siderophore synthesis system.

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Tissue niche influences immune and metabolic profiles to Staphylococcus aureus biofilm

Project description:Infection is a devastating post-surgical complication, often necessitating additional procedures and prolonged antibiotic therapy. This is especially relevant for craniotomy and prosthetic joint infections, both of which are characterized by biofilm formation on the bone or implant surface, respectively, with S. aureus representing a primary cause. The effectiveness of immune responses to these infections is predicated on both host- and pathogen-derived signals in the infection microenvironment. However, the extent to which these signals differ across distinct tissue niches and influence immune function remains relatively unknown. Using mouse models of S. aureus craniotomy and prosthetic joint infection complemented with patient samples from both infectious modalities, we show profound metabolomic, transcriptomic, and functional differences that are dependent on tissue niche. These signatures were both spatially and temporally distinct, differing not only between surgical site infections but evolving over time within a single model. These findings highlight the unique immune attributes of biofilms that are heavily influenced by the local tissue microenvironment, which will likely have important implications when designing therapeutic approaches to target specific infections.

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Project description:In situ Staphylococcus aureus gene expression in a human prosthetic joint infection

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Staphylococcus aureus gene expression during infection and antibiotic treatment with moxifloxacin in a guinea pig biofilm infection model

Project description:Staphylococcus aureus is a major agent in device related infections. Upon infection, it upregulates virulence factors and adapts to host environment. We investigated the gene expression profile of S. aureus in a guinea pig infection model. Four Teflon® cages were placed subcutaneously in each of 12 animals prior to inoculation of a S. aureus strain from a patient with prosthetic joint infection (PJI). The animals were divided into two groups of six, one treated with moxifloxacin after three days of infection and for four days, and the other untreated. Cage fluid and cages were collected for RNA sequencing analysis and metabolomics. The gene expression profiles in untreated controls on day 7 and 9 were not differentiable and resemble the profile reported for the PJI case from where the strain originated. Compared to the profiles from day 3, we found upregulation of ammonia production through urea degradation, arginine deiminase and acetoin biosynthesis pathways on day 7 and 9, while several virulence genes were downregulated. Interestingly, the transcriptome seven day after termination of moxifloxacin treatment resembled infection day 3. Overall, the gene expression profiles showed adaptation to hypoxic and acidic environment during infection development. We deem the model to be suitable for pathogenesis studies.

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