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Staphylococcus aureus multiplexes death-effector deoxyribonucleosides to neutralize phagocytes

ABSTRACT: Staphylococcus aureus multiplexes death-effector deoxyribonucleosides to neutralize phagocytes

PROVIDER: PRJEB50054 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR7996874_1.fastq.gz	Fastqsanger.gz
	ERR7996874_2.fastq.gz	Fastqsanger.gz
	ERR7996875_1.fastq.gz	Fastqsanger.gz
	ERR7996875_2.fastq.gz	Fastqsanger.gz
	ERR7996876_1.fastq.gz	Fastqsanger.gz

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<i>Staphylococcus aureus</i> Multiplexes Death-Effector Deoxyribonucleosides to Neutralize Phagocytes.

Project description:Adenosine synthase A (AdsA) is a key virulence factor of Staphylococcus aureus, a dangerous microbe that causes fatal diseases in humans. Together with staphylococcal nuclease, AdsA generates deoxyadenosine (dAdo) from neutrophil extracellular DNA traps thereby igniting caspase-3-dependent cell death in host immune cells that aim at penetrating infectious foci. Powered by a multi-technological approach, we here illustrate that the enzymatic activity of AdsA in abscess-mimicking microenvironments is not restricted to the biogenesis of dAdo but rather comprises excessive biosynthesis of deoxyguanosine (dGuo), a cytotoxic deoxyribonucleoside generated by S. aureus to eradicate macrophages of human and animal origin. Based on a genome-wide CRISPR-Cas9 knock-out screen, we further demonstrate that dGuo-induced cytotoxicity in phagocytes involves targeting of the mammalian purine salvage pathway-apoptosis axis, a signaling cascade that is concomitantly stimulated by staphylococcal dAdo. Strikingly, synchronous targeting of this route by AdsA-derived dGuo and dAdo boosts macrophage cell death, indicating that S. aureus multiplexes death-effector deoxyribonucleosides to maximize intra-host survival. Overall, these data provide unique insights into the cunning lifestyle of a deadly pathogen and may help to design therapeutic intervention strategies to combat multidrug-resistant staphylococci.

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Project description:Staphylococcus aureus is one of the most important pathogens in humans and animals, multiply resistant strains are increasingly widespread, new agents are needed for the treatment of S. aureus. Rhein, a natural plant product, has potential antimicrobial activity against Staphylococcus aureus. We employed Affymetrix Staphylococcus aureus GeneChipsTM arrays to investigate the global transcriptional profiling of Staphylococcus aureus ATCC25923 treated with rhein. Results provided insight into mechanisms involved in rhein - Staphylococcus aureus interactions. Keywords: rhein response

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