Unknown

Dataset Information

0

Coagulase-negative staphylococci release a purine analog that inhibits Staphylococcus aureus virulence.


ABSTRACT: Coagulase-negative staphylococci and Staphylococcus aureus colonize similar niches in mammals and conceivably compete for space and nutrients. Here, we report that a coagulase-negative staphylococcus, Staphylococcus chromogenes ATCC43764, synthesizes and secretes 6-thioguanine (6-TG), a purine analog that suppresses S. aureus growth by inhibiting de novo purine biosynthesis. We identify a 6-TG biosynthetic gene cluster in S. chromogenes and other coagulase-negative staphylococci including S. epidermidis, S. pseudintermedius and S. capitis. Recombinant S. aureus strains harbouring this operon produce 6-TG and, when used in subcutaneous co-infections in mice with virulent S. aureus USA300, protect the host from necrotic lesion formation. Used prophylactically, 6-TG reduces necrotic skin lesions in mice infected with USA300, and this effect is mediated by abrogation of toxin production. RNAseq analyses reveal that 6-TG downregulates expression of genes coding for purine biosynthesis, the accessory gene regulator (agr) and ribosomal proteins in S. aureus, providing an explanation for its effect on toxin production.

SUBMITTER: Chin D 

PROVIDER: S-EPMC7994395 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC107820 | biostudies-literature
| S-EPMC3486100 | biostudies-literature
| S-EPMC90505 | biostudies-literature
| S-EPMC134988 | biostudies-literature
| S-EPMC6429511 | biostudies-literature
| S-EPMC7284987 | biostudies-literature
| S-EPMC6671284 | biostudies-literature
| S-EPMC1855542 | biostudies-literature
| S-EPMC10823624 | biostudies-literature
| S-EPMC7402503 | biostudies-literature