Staphylococcus aureus nonribosomal peptide secondary metabolites regulate virulence.
Staphylococcus aureus is a major human pathogen that is resistant to numerous antibiotics in clinical use. We found two nonribosomal peptide secondary metabolites--the aureusimines, made by S. aureus--that are not antibiotics, but function as regulators of virulence factor expression and are necessary for productive infections. In vivo mouse models of bacteremia showed that strains of S. aureus unable to produce aureusimines were attenuated and/or cleared from major organs, including the spleen, liver, and heart. Targeting aureusimine synthesis may offer novel leads for anti-infective drugs.
Department of Biochemistry and Biomedical Sciences, M. G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
Morgan A
MA
Wyatt
Wenliang
W
Wang
Christelle M
CM
Roux
Federico C
FC
Beasley
David E
DE
Heinrichs
Paul M
PM
Dunman
Nathan A
NA
Magarvey
D000595:Amino Acid Sequence; D000818:Animals; D016470:Bacteremia / Q000382:microbiology; D004151:Dipeptides / Q000737:chemistry / Q000302:isolation & purification; D006321:Heart / Q000382:microbiology; D006461:Hemolysis; D008099:Liver / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D046908:Peptide Biosynthesis, Nucleic Acid-Independent; D010453:Peptide Synthases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011719:Pyrazines / Q000737:chemistry / Q000378:metabolism*; D013154:Spleen / Q000382:microbiology; D013203:Staphylococcal Infections / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism* / Q000472:pathogenicity*; D037521:Virulence Factors / Q000378:metabolism*
D004151:Dipeptides; D011719:Pyrazines; D037521:Virulence Factors; C551205:aureusimine A; C096976:phevalin; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase