Long-Time Persistence of Superantigen-Producing Staphylococcus aureus Strains in the Intestinal Microflora of Healthy Infants

Abstract

Staphylococcus aureus has been isolated at an increasing rate from infants' stools during the last decades, but it is not known whether this species can colonize and persist in the intestinal microflora. To investigate this, 49 Swedish infants were followed prospectively from birth until 12 months of age. S. aureus was identified in a rectal swab obtained 3 d after delivery and in quantitative cultures of fecal samples collected at 1, 2, 4, and 8 weeks and at 6 and 12 months of age. A random amplified polymorphic DNA (RAPD) method was developed to distinguish individual S. aureus strains from one another and the strains were tested for production of enterotoxins A-D and TSST-1. By 3 days of age, 16% of infants had S. aureus in their intestines, which increased to 73% by 2-6 months, whereafter it decreased slightly to 53%. At the same time S. aureus population counts in colonized infants declined from an average 10 6.8 CFU/g feces during the first months of life to 10 4.0 CFU/g feces by 12 months. Colonized infants usually harbored one or two S. aureus strains in their microflora for long periods of time. Few strains were transient passengers and the median time of persistence of S. aureus strains in the microflora was several months. Of the 75 S. aureus strains identified, 43% produced one or more toxins: 13% SEA, 7% SEB, 23% SEC, 4% SED, and 11% TSST-1. Altogether, 47% of the investigated infants were colonized by a toxin-producing S. aureus during their first year of life. Despite this they were apparently healthy and did not have more gastrointestinal problems than noncolonized infants. This report is the first to show that S. aureus may be a resident member of the normal intestinal microflora in infancy. Abbreviations CFU, colony-forming units TSST-1, toxic shock syndrome toxin-1 RAPD, random amplified polymorphic DNA Bacteria start to colonize the skin, respiratory tract, and intestines as soon as the newborn has left the sterile womb. With time, a complex ecosystem develops known as the normal microflora (1). Staphylococcus aureus colonizes the anterior nares of more than 50% of young infants (2-5). During the last decades, S. aureus has also been isolated at an increasing rate from fecal samples of infants in Western societies. Thus, only 1 out of 13 infants had S. aureus in their stools in a study performed in England in the 1980s (6), but 30% in a Swedish study published 1985 (7) and 53% in Sweden in the late 1990s (8). It is not known whether staphylococci persist and replicate in the intestines or if S. aureus in the stools represent bacteria transiently passing the intestines after having been swallowed. If infants are colonized by S. aureus in their intestines, it may have medical consequences. S. aureus strains can produce a range of different exotoxins, among them the enterotoxins, which cause vomiting with or without diarrhea and are responsible for staphylococcal food poisoning (9). The enterotoxins, together with toxic shock syndrome toxin-1, also function as "superantigens." By binding to both...

Neonatal exposure to staphylococcal superantigen improves induction of oral tolerance in a mouse model of airway allergy

“…Of S. aureus strains colonising the neonatal gut, approximately 45% have the capacity to produce a toxin with superantigenic function [16,17]. We have not noted any untoward effect of such colonisation, as parents report no increased prevalence of gastro-intestinal or other symptoms [17]. Quite unexpectedly, we instead found that infants colonised in the first week(s) of life with S. aureus had significantly decreased risk of developing food allergy [20].…”

“…Statistics from SEA pretreated OVA-fed mice as compared with sham-treated OVA-fed mice are shown as à po0.05. SEA is the most potent superantigen [32] and because SEAproducing strains are more common than SEB-producing strains in the gut flora of Swedish children [17], SEA was used in this study. However, we also investigated the effect of SEB pretreatment in our model of oral tolerance and airway allergy and found that SEB was less effective and less reliable in improving oral tolerance compared with SEA (unpublished data).…”

“…However, we have recently observed that S. aureus has become a quite common inhabitant of the gut microbiota in Swedish infants [16,17], probably as a result of decreased competition from ''classical'' faecal bacteria, whose circulation has decreased strongly in today's highly hygienic hospitals and homes [18,19]. Of S. aureus strains colonising the neonatal gut, approximately 45% have the capacity to produce a toxin with superantigenic function [16,17]. We have not noted any untoward effect of such colonisation, as parents report no increased prevalence of gastro-intestinal or other symptoms [17].…”

“…aureus is foremost a skin bacterium and has previously been incriminated in the pathogenesis of eczema, because S. aureus are often found colonising eczematous skin lesions, aggravating the lesion and because IgE antibodies to S. aureus superantigen may be found in such cases [15]. However, we have recently observed that S. aureus has become a quite common inhabitant of the gut microbiota in Swedish infants [16,17], probably as a result of decreased competition from ''classical'' faecal bacteria, whose circulation has decreased strongly in today's highly hygienic hospitals and homes [18,19]. Of S. aureus strains colonising the neonatal gut, approximately 45% have the capacity to produce a toxin with superantigenic function [16,17].…”

Expression of toxic shock syndrome toxin-1 gene of Staphylococcus aureus in milk: Proof of concept

“…Superantigenic-producing S. aureus incorporated into the digestive tracts might cause enterocolitis (Watanabe et al, 2001) and persist for a long time in the intestinal microbiota of infants (Lindberg et al, 2000). Enteric TSST-1 activates systemic T cells and leads to a dysregulated, but exuberant immunological activity causing the remission and flare-up cycle of mucosal inflammation in patients with ulcerative colitis (Shiobara et al, 2007).…”