Vaginal Community State Types (CSTs) Alter Environmental Cues and Production of theStaphylococcus aureusToxic Shock Syndrome Toxin-1 (TSST-1)

Abstract

ABSTRACTMenstrual toxic shock syndrome (mTSS) is a rare but life-threatening disease associated with use of high-absorbency tampons. The production of theStaphylococcus aureustoxic shock syndrome toxin-1 (TSST-1) is involved in nearly all cases of mTSS and is tightly controlled by regulators responding to the environment. In the prototypic mTSS strainS. aureusMN8, the major repressor of TSST-1 is the carbon catabolite protein A (CcpA), which responds to glucose concentrations in the vaginal tract. Healthy vaginalLactobacillusspecies also depend on glucose for both growth and acidification of the vaginal environment through lactic acid production. We hypothesized that interactions between the vaginal microbiota (herein referred to as Community State Types, or CSTs) and MN8 depend on environmental cues, and that these interactions subsequently affect TSST-1 production. Using MN8 Δ1ccpAat various glucose levels, we demonstrate that the supernatants from different CSTs grown in vaginally defined media (VDM) significantly decreasetstexpression. When co-culturing CST species with MN8 ΔccpA, we show thatL. jenseniicompletely inhibits TSST-1 production in conditions mimicking healthy menstruation or mTSS. Finally, we show that growingS. aureusin “unhealthy” or “transitional” CST supernatants results in higher IL-2 production from T cells. These findings suggest that dysbiotic CSTs may encourage TSST-1 production in the vaginal tract, and further indicates that the CSTs are likely important for the development of mTSS.IMPORTANCEIn this study, we investigate the impact of the vaginal microbiota againstS. aureusin conditions mimicking the vaginal environment at various stages of the menstrual cycle. We demonstrate thatL. jenseniican inhibit TSST-1 production, suggesting the potential for probiotic activity in treating mTSS. On the other side of the spectrum, “unhealthy” or “transient” bacteria such asG. vaginalisandL. inerssupport more TSST-1 production byS. aureus, suggesting that CSTs are important in the development of mTSS. This study sets forward a model for examining contact-independent interactions between pathogenic bacteria and the vaginal microbiota. It also demonstrates the necessity of replicating the environment when studying one as dynamic as the vagina.