The production of the staphylococcal exotoxin toxic shock syndrome toxin-1 (TSST-1) by
Staphylococcus aureushas been associated with essentially all cases of menstruation-associated toxic shock syndrome (TSS). In this work, we show that the human vaginal isolate Lactobacillus reuteriRC-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. aureusMN8, a prototype of menstrual TSS S. aureusstrains. Quantitative real-time PCR data showed that transcription from the P tstpromoter, as well as the P2 and P3 promoters of the agrsystem from all four agrsubgroups of S. aureus, was strongly inhibited in response to growth with L. reuteriRC-14 cultural supernatant. Alterations in the transcriptional levels of two other virulence-associated regulators sarAand saeRSwere also observed, indicating a potential overall influence of L. reuteriRC-14 signals on the production of virulence factors in S. aureus. S. aureuspromoter- luxreporter strains were used to screen biochemically fractionated L. reuteriRC-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 Lactobacillusand Staphylococcus, and provide a unique mechanism by which endogenous or probiotic strains may attenuate virulence factor production by bacterial pathogens.