title: Lactobacillus reuteri-produced cyclic dipeptides quench agr-mediated expression of toxic shock syndrome toxin-1 in staphylococci.
abstract: The production of the staphylococcal exotoxin toxic shock syndrome toxin-1 (TSST-1) by Staphylococcus aureus has been associated with essentially all cases of menstruation-associated toxic shock syndrome (TSS). In this work, we show that the human vaginal isolate Lactobacillus reuteri RC-14 produces small signaling molecules that are able to interfere with the staphylococcal quorum-sensing system agr, a key regulator of virulence genes, and repress the expression of TSST-1 in S. aureus MN8, a prototype of menstrual TSS S. aureus strains. Quantitative real-time PCR data showed that transcription from the Ptst promoter, as well as the P2 and P3 promoters of the agr system from all four agr subgroups of S. aureus, was strongly inhibited in response to growth with L. reuteri RC-14 cultural supernatant. Alterations in the transcriptional levels of two other virulence-associated regulators sarA and saeRS were also observed, indicating a potential overall influence of L. reuteri RC-14 signals on the production of virulence factors in S. aureus. S. aureus promoter-lux reporter strains were used to screen biochemically fractionated L. reuteri RC-14 supernatant, and the cyclic dipeptides cyclo(L-Phe-L-Pro) and cyclo(L-Tyr-L-Pro) were identified as the signaling molecules. The results from this work contribute to a better understanding of interspecies cell-to-cell communication between Lactobacillus and Staphylococcus, and provide a unique mechanism by which endogenous or probiotic strains may attenuate virulence factor production by bacterial pathogens.
authors.affiliation: Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada N6A 5C1.
authors.forename: Jingru
authors.initials: J
authors.lastname: Li
authors.forename: Wenliang
authors.initials: W
authors.lastname: Wang
authors.forename: Stacey X
authors.initials: SX
authors.lastname: Xu
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Magarvey
authors.forename: John K
authors.initials: JK
authors.lastname: McCormick
mesh_terms: D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors*; D002450:Cell Communication; D004151:Dipeptides / Q000096:biosynthesis / Q000494:pharmacology*; D004768:Enterotoxins / Q000037:antagonists & inhibitors*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D052200:Limosilactobacillus reuteri / Q000378:metabolism*; D008598:Menstruation; D019936:Probiotics; D053038:Quorum Sensing; D012772:Shock, Septic / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000472:pathogenicity*; D018089:Superantigens; D015534:Trans-Activators / Q000037:antagonists & inhibitors* / Q000235:genetics; D014621:Vagina / Q000382:microbiology*
chemical_list: C095698:Agr protein, Staphylococcus aureus; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004151:Dipeptides; D004768:Enterotoxins; D018089:Superantigens; D015534:Trans-Activators; C030107:enterotoxin F, Staphylococcal