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.
Wyatt
Morgan A
MA
Department of Biochemistry and Biomedical Sciences, M. G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
Wang
Wenliang
W
Roux
Christelle M
CM
Beasley
Federico C
FC
Heinrichs
David E
DE
Dunman
Paul M
PM
Magarvey
Nathan A
NA
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