Identification and Characterization of a Novel Staphylococcal Emetic Toxin

Abstract

e Staphylococcal enterotoxins (SEs) produced by Staphylococcus aureus have superantigenic and emetic activities, which cause toxic shock syndrome and staphylococcal food poisoning, respectively. Our previous study demonstrated that the sequence of SET has a low level of similarity to the sequences of other SEs and exhibits atypical bioactivities. Hence, we further explored whether there is an additional SET-related gene in S. aureus strains. One SET-like gene was found in the genome of S. aureus isolates that originated from a case of food poisoning, a human nasal swab, and a case of bovine mastitis. The deduced amino acid sequence of the SET-like gene showed 32% identity with the amino acid sequence of SET. The SET-like gene product was designated SElY. In the food poisoning and nasal swab isolates, mRNA encoding SElY was highly expressed in the early log phase of cultivation, whereas a high level of expression of this mRNA was found in the bovine mastitis isolate at the early stationary phase. To estimate whether SElY has both superantigenic and emetic activities, recombinant SElY was prepared. Cell proliferation and cytokine production were examined to assess the superantigenic activity of SElY. SElY exhibited superantigenic activity in human peripheral blood mononuclear cells but not in mouse splenocytes. In addition, SElY exhibited emetic activity in house musk shrews after intraperitoneal and oral administration. However, the stability of SElY against heating and pepsin and trypsin digestion was different from that of SET and SEA. From these results, we identified SElY to be a novel staphylococcal emetic toxin. Staphylococcus aureus produces a variety of exotoxins, including staphylococcal enterotoxins (SEs) and toxic shock syndrome toxin 1 (TSST-1) (1). These toxins are superantigens, which have the ability to stimulate a large repertoire of the V␤ elements of T cell receptor (TCR)-bearing T cells. SEs are also emetic toxins causing staphylococcal food poisoning in humans, although the mechanism of SE-induced emesis has not been entirely verified (2). Due to these properties, SEs are assumed to be a menace to public health. Five major serological types (SEA to SEE) have been characterized (2), and new types of SE-related toxins (SEG to SEI, SElJ, SEK to SET, SElU, SElV, and SElX) have recently been reported (2-8). Moreover, superantigen-related genes, such as staphylococcal superantigen-like protein (SSL) genes (ssl1 to ssl26), were discovered during determination of the complete genome sequences of several S. aureus strains (9-11). It has been recognized that the superantigen genes are associated with mobile genetic elements (MGEs), such as pathogenicity islands, prophages, or plasmids (5,(11)(12)(13)(14). This fact implies that these superantigen genes move among S. aureus strains by horizontal transfer and that such MGEs play an important role in the evolution of S. aureus as a pathogen.We have reported that SET shows mitogenicity to human T cells and requires major histocompatibility complex (MHC) cla...

Food-Borne Outbreak Investigation and Molecular Typing: High Diversity of Staphylococcus aureus Strains and Importance of Toxin Detection

“…To date, 23 distinct SEs have been described based on their antigenicity and these are referred to as SEA to SElY in the chronological order of their discovery [2,4]. Only a subset of SEs possesses emetic activities [3,4,5].…”

“…To date, 23 distinct SEs have been described based on their antigenicity and these are referred to as SEA to SElY in the chronological order of their discovery [2,4]. Only a subset of SEs possesses emetic activities [3,4,5]. Among the 23 SEs identified and reported in literature, only five SEs (SEA, SEB, SEC, SED and SEE) have been well characterized, and are detectable using commercially available assays or in-house developed methods [6,7].…”

Staphylococcal Toxic Shock Syndrome Caused By An Intravaginal Product. A Case Report

“…One of the toxins produced by SA is an enterotoxin with superantigenic and emetic effects [10] and which was identified as the toxin responsible for the vomiting symptoms in these cases.…”

Biological toxins of potential bioterrorism risk: Current status of detection and identification technology

“…To date, more than 20 variants of SE toxins and SE-like toxins have been identified ranging from SEA to SElY (Table 1, [46,47]). The superantigenic as well as emetic actions have been proven for SEs, whereas for the SE-like toxins, the superantigenic activity has been confirmed but their individual emetic activity has not yet been demonstrated.…”