Influence of the vaginal microbiota on toxic shock syndrome toxin 1 production by Staphylococcus aureus

Abstract

Menstrual toxic shock syndrome (TSS) is a serious illness that afflicts women of premenopausal age worldwide and arises from vaginal infection by Staphylococcus aureus and concurrent production of toxic shock syndrome toxin-1 (TSST-1). Studies have illustrated the capacity of lactobacilli to reduce S. aureus virulence, including the capacity to suppress TSST-1. We hypothesized that an aberrant microbiota characteristic of pathogenic bacteria would induce the increased production of TSST-1 and that this might represent a risk factor for the development of TSS. A S. aureus TSST-1 reporter strain was grown in the presence of vaginal swab contents collected from women with a clinically healthy vaginal status, women with an intermediate status, and those diagnosed with bacterial vaginosis (BV). Bacterial supernatant challenge assays were also performed to test the effects of aerobic vaginitis (AV)-associated pathogens toward TSST-1 production. While clinical samples from healthy and BV women suppressed toxin production, in vitro studies demonstrated that Streptococcus agalactiae and Enterococcus spp. significantly induced TSST-1 production, while some Lactobacillus spp. suppressed it. The findings suggest that women colonized by S. aureus and with AV, but not BV, may be more susceptible to menstrual TSS and would most benefit from prophylactic treatment.

Fig 1

Vaginal microbiota of 21 subjects recruited from the clinical study, as determined through 16S rRNA sequencing by Illumina. Vaginal state was determined via Nugent scoring and measurement of pH: a score of 1 to 3 is healthy, one of 4 to 6 is intermediate, and one of 7 to 10 is BV. Each column represents a participant (marked by their corresponding identification [ID] number), with each colored bar representing a type of bacterium.

Fig 2

Luminescence activity of the S. aureus MN8 tst gene in response to vaginal swab contents from women with various types of vaginal health (healthy, intermediate, and BV). (A) Vaginal swab samples from all 3 health groups were capable of suppressing tst expression, as shown by three representative samples. (B, C) Two clinical samples from the healthy group failed to suppress tst expression. S, Staphylococcus aureus MN8; numbers, participant identification number; TM, transport medium, the medium in which the swabs were preserved.

Fig 3

Fold change in gene expression of tst in S. aureus MN8 in response to supernatants from lactobacilli (A), AV-associated bacteria (B), and BV-associated bacteria (C), detected by real-time PCR. *, P < 0.05.