Dual toxic-peptide-coding Staphylococcus aureus RNA under antisense regulation targets host cells and bacterial rivals unequally.
Produced from the pathogenicity islands of Staphylococcus aureus clinical isolates, stable SprG1 RNA encodes two peptides from a single internal reading frame. These two peptides accumulate at the membrane, and inducing their expression triggers S. aureus death. Replacement of the two initiation codons by termination signals reverses this toxicity. During growth, cis-antisense RNA SprF1 is expressed, preventing mortality by reducing SprG1 RNA and peptide levels. The peptides are secreted extracellularly, where they lyse human host erythrocytes, a process performed more efficiently by the longer peptide. The two peptides also inactivate Gram-negative and -positive bacteria, with the shorter peptide more effective against S. aureus rivals. Two peptides are secreted from an individual RNA containing two functional initiation codons. Thus, we present an unconventional type I toxin-antitoxin system expressed from a human pathogen producing two hemolytic and antibacterial peptides from a dual-coding RNA, negatively regulated by a dual-acting antisense RNA.
Rennes University, Inserm U835 Biochimie Pharmaceutique, 2 Avenue du Professeur Léon Bernard, 35043 Rennes, France.
Marie-Laure
ML
Pinel-Marie
Rennes University, Inserm U835 Biochimie Pharmaceutique, 2 Avenue du Professeur Léon Bernard, 35043 Rennes, France.
Régine
R
Brielle
Rennes University, Inserm U835 Biochimie Pharmaceutique, 2 Avenue du Professeur Léon Bernard, 35043 Rennes, France. Electronic address: brice.felden@univ-rennes1.fr.
Brice
B
Felden
D000595:Amino Acid Sequence; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism* / Q000633:toxicity; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism* / Q000633:toxicity; D004912:Erythrocytes / Q000187:drug effects / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial; D054884:Host-Pathogen Interactions; D006801:Humans; D008969:Molecular Sequence Data; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D016372:RNA, Antisense / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*
D001425:Bacterial Outer Membrane Proteins; D001427:Bacterial Toxins; D016372:RNA, Antisense; D012333:RNA, Messenger