Abdulrahman T. Saadi

Factors enhancing adherence of toxigenic Staphylococcus aureus to epithelial cells and their possible role in sudden infant death syndrome

Toxigenic strains of Staphylococcus aureus have been suggested to play a role in sudden infant death syndrome (SIDS). In this study we examined two factors that might enhance binding of toxigenic staphylococci to epithelial cells of infants in the age range in which cot deaths are prevalent: expression of the Lewis(a) antigen and infection with respiratory syncytial virus (RSV). By flow cytometry we demonstrated that binding of three toxigenic strains of S. aureus to cells from nonsecretors was significantly greater than to cells of secretors. Pre-treatment of epithelial cells with monoclonal anti-Lewis(a) or anti-type-1 precursor significantly reduced bacterial binding (P < 0.01); however, attachment of the bacteria correlated only with the amount of Lewis(a) antigen detected on the cells (P < 0.01). HEp-2 cells infected with RSV bound significantly more bacteria than uninfected cells. These findings are discussed in context of factors previously associated with SIDS (mothers smoking, bottle feeding and the prone sleeping position) and a hypothesis proposed to explain some cases of SIDS.

The potential role of bacterial toxins in Sudden Infant Death Syndrome (SIDS)

SummaryToxigenic bacteria have been implicated in some cases of Sudden Infant Death Syndrome (SIDS). Although there is not much evidence thatClostridia spp. are associated with SIDS in Britain, strains ofStaphylococcus aureus producing pyrogenic toxins have been isolated from significant numbers of these infants at autopsy. The pyrogenic toxins, produced by some strains of group AStreptococcus pyogenes as well as staphylococci, are powerful “superantigens” that have significant physiological effects including induction of fever > 38°C. In this article, interactions between genetic and environmental factors that might enhance colonization of epithelial surfaces by toxigenic staphylococci are analyzed: infants expression of Lewisa antigen which acts as a receptor for some microorganisms; viral infections; the effect of mothers smoking on susceptibility to respiratory infection. Based on epidemiological findings and laboratory investigations, a hypothesis is proposed to explain how bacteria producing pyrogenic toxins might contribute to some cot deaths.ZusammenfassungIn einigen Fällen des Sudden Infant Death Syndrom (SIDS) wurde die Rolle Toxin bildender Bakterien diskutiert. Obwohl es keinen Beweis gibt, daß Clostridia spp. mit SIDS in Großbritanien assoziiert sind, sind von signifikanter Anzahl dieser Kinder bei der Autopsie Stämme von Stapylokkokus aureus isoliert worden, welche Fieber erzeugende Toxine produzieren. Die Fieber erzeugenden Toxine, welche von einigen Stämmen der Gruppe A Streptokkokus pyogenes produziert werden, wie auch von Staphylokkoken, sind mächtige „Superantigene”, welche signifikante physiologische Effekte haben unter Einbeziehung der Induktion von Fieber mit mehr als 38°C. In diesem Artikel werden Interaktionen zwischen genetischen und Umgebungsfaktoren erörtert, welche die Kolonisierung epithelialer Oberflächen durch Toxin bildende Staphylokkoken steigern könnten: die Expression des Lewisa Antigens des Kindes, welches als Rezeptor für einige Mikroorganismen wirksam ist; virale Infektionen; die Auswirkung des mütterlichen Rauchens auf die Empfänglichkeit für Atemwegsinfektionen. Basierend auf epidemiologischen Befunden und Laboratoriumsuntersuchungen wird eine Hypothese vorgeschlagen, wie Bakterien; welche pyrogene Toxine produzieren, zu einigen plötzlichen Kindstodesfällen beitragen könnten.

Lewis antigen expression on human monocytes and binding of pyrogenic toxins.

Toxigenic bacteria such asBordetella pertussis andStaphylococcus aureus have been implicated in some cases of sudden infant death syndrome (SIDS). We have previously demonstrated that the Lewisa antigen is an epithelial cell receptor forS. aureus, and this study demonstrated that Lewisa on human monocytes is also a receptor for staphylococcal enterotoxin B (SEB). Values obtained in assays for production of TNF-alpha and nitric oxide were greater for monocytes treated with SEB compared with those treated with lipopolysaccharide (LPS). Exposure to LPS increased the expression of Lewisa on monocytes. These results are discussed with reference to the reported enhancement of endotoxic shock by pyrogenic toxins.

Adhesins Of Staphylococcus Aureus that Bind Lewisa Antigen

Sudden Infant Death Syndrome (SIDS) is defined as “the sudden death of any infant or young child which is unexpected by history, and in which a thorough postmortem examination fails to demonstrate an adequate cause of death” [Beckwith, 1969]. Since 1990, there has been a steady reduction in the numbers of SIDS in Britain [Court, 1995; Scottish Cot Death Trust, personal communication]; however, SIDS is still the major cause of post perinatal mortality during the first year of life. Petechiae in the lungs and thymus, liquid heart blood and empty bladder are common findings at autopsy [Berry, 1992]. While there is little evidence that could explain why the infant died, there are common findings that suggest immune or inflammatory reactions have been elicited before death(Table 1).

Assessment of Lewis blood group antigens and secretor status in autopsy specimens

The ability of enzyme linked immunosorbent assays (ELISA) to detect Lewis and H antigens in secretions obtained from 280 autopsies was assessed. The ELISA results were compared with those for matched blood specimens examined by agglutination of erythrocytes by monoclonal anti-Lewis(a) and anti-Lewis(b) antibodies. There was good agreement between the results for the two tests and the ELISAs could be used to determine secretor status of the subject. While determination of ABO group with monoclonal anti-A and anti-B was possible even with lysed blood, the results for Lewis typing by erythrocyte agglutination were poor if the sample was lysed or partially lysed. Detection of the antigens by ELISA was as efficient among elderly subjects as among younger ones and both H and Lewis antigens could be detected on erythrocytes and in secretions up to 127 h after death.