Reduction in Staphylococcus aureus growth and exotoxin production and in vaginal interleukin 8 levels due to glycerol monolaurate in tampons.

BACKGROUND: Staphylococcal menstrual toxic shock syndrome depends on vaginal production of exotoxins. Glycerol monolaurate (GML) inhibits Staphylococcus aureus exotoxin production in vitro. The purpose of this study was to determine whether GML, as a tampon fiber finish, inhibits production of exotoxins and the cytokine interleukin 8 (IL-8) during normal tampon use. METHODS: On day 2 of menstruation, when vaginal S. aureus counts are high in colonized women, study participants exchanged their own preferred tampons, after wearing them for 2-6 h, for study tampons with or without GML (assigned randomly and blindly), which they then wore for 4-6 h. The women's own tampons and the study tampons with or without GML were assayed for S. aureus, the exotoxins toxic shock syndrome toxin 1 and alpha-toxin, and IL-8. RESULTS: A total of 225 women completed the study. S. aureus was present in the tampons of 41 women (18%). Lower numbers of S. aureus and the exotoxins were detected in study tampons with or without GML than in women's own tampons; lower amounts of the exotoxins were present in study tampons with GML than study tampons without GML. The IL-8 level was lower in tampons from women without vaginal S. aureus compared with women with S. aureus and was lower in study tampons with GML than in study tampons without GML. CONCLUSIONS: Tampons that contain GML reduce S. aureus exotoxin production. S. aureus increases vaginal IL-8 levels, and GML reduces production of this proinflammatory cytokine. These results suggest that GML added to tampons provides additional safety relative to menstrual toxic shock syndrome as well as benefits for vaginal health generally, thus supporting the addition of GML to tampons.

Superantigen profile of Staphylococcus aureus isolates from patients with steroid-resistant atopic dermatitis.

BACKGROUND: Superantigens induce skin inflammatory responses in atopic dermatitis, which is commonly associated with Staphylococcus aureus infection. T cells activated in vitro by superantigens become steroid resistant. The objective was to assess the superantigen profiles of S. aureus isolates from patients with steroid-resistant atopic dermatitis. METHODS: We compared the superantigen-production capability of S. aureus isolates from 78 patients with steroid-resistant atopic dermatitis (group 1) with that of 30 vaginal isolates from healthy women (group 2) and 22 isolates from a general population of patients with atopic dermatitis (group 3). Polymerase chain reaction with primers for superantigens, combined with selected antibody testing, was used to analyze the presence of toxic shock syndrome toxin 1, staphylococcal enterotoxins, and enterotoxin-like superantigens. RESULTS: S. aureus isolates from group 1 had a statistically significant difference in superantigen profile, compared with the profiles of group 2 and group 3 isolates. Group 2 isolates were similar in profile to group 3 isolates, with 4 and 5 superantigens per isolate, respectively. In contrast, group 1 isolates produced a mean of 8 superantigens each (P<<.001, for comparison with group 2 or group 3). These group 1 isolates were more likely to produce the 3 major toxic shock syndrome-associated superantigens (toxic shock syndrome toxin 1, staphylococcal enterotoxin B, and staphylococcal enterotoxin C) and to produce unusual combinations of superantigens (e.g., toxic shock syndrome toxin 1 and staphylococcal enterotoxin B). CONCLUSIONS: S. aureus isolates from patients with steroid-resistant atopic dermatitis appear to be selected on the basis of greater production of superantigens, compared with that of isolates from control groups. Superantigens may offer selective advantages for colonization of patients.

Molecular analysis of staphylococcal superantigens.

Staphylococcal superantigens (SAgs) comprise a large family of exotoxins produced by Staphylococcus aureus strains. These exotoxins are important in a variety of serious human diseases, including menstrual and nonmenstrual toxic shock syndrome (TSS), staphylococcal pneumonias, and a recently described staphylococcal purpura fulminans. In addition, these SAg exotoxins are being increasingly recognized for their possible roles in many other human diseases, such as atopic dermatitis, Kawasaki syndrome, nasal polyposis, and certain autoimmune disorders. To clarify the full spectrum of human diseases caused by staphylococcal SAgs, it is necessary to have assays for them. At present there are 17 well-characterized, serologically distinct SAgs made by S. aureus: TSS toxin-1; staphylococcal enterotoxins (SEs) A, B, C (multiple minor variant forms exist), D, E, and I; and SE-like G, H, J, K, L, M, N, O, P, and Q. In addition, SE-like proteins R, S, T, and U have been identified but remain poorly characterized. The most straightforward way to analyze S. aureus strains for the well-characterized SAgs is through polymerase chain reaction for their genes; we provide here our method for this analysis. Although it would be ideal to confirm that all of the same SAgs are produced by S. aureus strains that have the genes, antibody reagents for SAg detection are only available for TSS toxin-1; SEs A-E; and enterotoxin-like proteins G, H, and Q. We provide a Western immunoblot procedure that allows in vitro quantification of these SAgs.

Vaginal Staphylococcus aureus superantigen profile shift from 1980 and 1981 to 2003, 2004, and 2005.

We determined vaginal Staphylococcus aureus superantigens. Staphylococci were quantified from tampons/diaphragms in 2003 to 2005, with counts compared to those determined in 1980 and 1981. In 2003 to 2005, more women were colonized than in 1980 and 1981 (23 versus 12%). Enterotoxins G and I and enterotoxin-like superantigens M and N declined, but enterotoxin-like superantigens K, L, and Q increased.

Sequence analysis of the Staphylococcus aureus srrAB loci reveals that truncation of srrA affects growth and virulence factor expression.

The SrrAB system regulates metabolism and virulence factors in Staphylococcus aureus. We sequenced the srrAB loci of 21 isolates and performed a phylogenetic analysis. Vaginal and bovine isolates clustered together, while skin isolates were genetically diverse. Few nucleotide polymorphisms were observed, and most were synonymous. Two strains (N2 and N19) with N-terminal truncations in SrrA displayed defects in growth and abnormally upregulated virulence factor expression under low-oxygen conditions.

Alpha and beta chains of hemoglobin inhibit production of Staphylococcus aureus exotoxins.

Prior studies suggest Staphylococcus aureus exotoxins are not produced when the organism is cultured in human blood. Human blood was fractionated into plasma and water-lysed red blood cells, and it was demonstrated that mixtures of alpha and beta globins of hemoglobin (as low as 1 mug/mL) inhibited S. aureus exotoxin production while increasing production of protein A and not affecting bacterial growth. Pepsin but not trypsin digestion destroyed the ability of alpha and beta globin to inhibit exotoxin production. Exotoxin production by both methicillin-resistant and methicillin-susceptible organisms was inhibited. Production of streptococcal pyrogenic exotoxin A by Streptococcus pyogenes was unaffected by alpha and beta globin chains but was inhibited when produced in S. aureus. Use of isogenic S. aureus strains suggested the targets of alpha and beta globin chains, leading to inhibition of staphylococcal exotoxins, included the two-component system SrrA-SrrB. delta hemolysin production was also inhibited, suggesting the two-component (and quorum sensing) system AgrA-AgrC was targeted. The alpha and beta globin chains represent promising molecules to interfere with the pathogenesis of serious staphylococcal diseases.