STAPHYLOCOCCUS AUREUS ENTEROTOXINS IN PEOPLE WITH CYSTIC FIBROSIS (CF).

Editor,

Staphylococcus aureus (SA) is a Gram-positive bacterium, which produces several enterotoxins inducing nausea. We hypothesize that patients with cystic fibrosis (CF) who are chronically infected with enterotoxin-producing SA in their airways may expectorate sputum containing enterotoxins, especially during sleeping, which may be ingested, subsequently leading to nausea. Therefore, we wished to examine if SA isolates obtained from CF sputum are enterotoxin-producers, which have the potential to cause nausea in their host.

We examined 16 clinical SA isolate from sputum of CF patients (n=16), who were infected with SA. SA cultures were examined for enterotoxins A, B, C, D and E by ELISA assay, in accordance with the manufacturer’s instructions RIDASCREEN® SET Total (R-Biopharm AG, Darmstadt, Germany). Of these, 10 (62.5%) isolates were positive for at least one enterotoxin, with the remaining six isolates negative for enterotoxin(s). There was no statistically significant difference (p=0.8) in lung function (FEV1%) between patientschronically/intermittently colonised with enterotoxin-producing SA strains and non enterotoxin-producing SA strains (Figure 1).

Figure 1.

Comparison of lung function (%FEV1) in patients with cystic fibrosis infected with enterotoxin-producing Staphylococcus aureus and non-enterotoxin-producing Staphylococcus aureus (p=0.82)

The exact amount of SEs required to produce emesis is not specific, largely due to individual variations in sensitivity to enterotoxins, however a study looking at a staphylococcal gastroenteritis outbreak discovered that doses of around 0.1μg of SEA were sufficient to produce nausea.1 A review in 2012 found that most studies quoted the total amount of SEs required for symptomatic gastroenteritis to occur to be around 0.1μg, however one exception suggested the figure to be as high as 10-20μg.2 In terms of numbers of enterotoxin- producing SA required to produce GI symptoms including nausea, this has been estimated to be circa 105 colony forming units (CFUs) per gram of food2. In the CF lung, previous work from our group has shown that with chronic SA infection, the mean number of organisms is 1.01 x 107 CFU per gram of sputum.3

In our CF population, 46.1% of adults and 44.7% of children are infected/colonised with SA. Data from the current study demonstrated that 62.5% of SA isolates were enterotoxin producers, equating to an occurrence of 28.8% and 27.9% SA enterotoxin-producers in adults and children, respectively. Interestingly, a study of 48 SA isolates from young and healthy Irish students between 1995 and 2004 found that 66.7% of isolates harboured the classical SE genes (SEA − SEE).4

Nausea in CF patients can be associated with several aetiologies, including distal intestinal obstruction syndrome (DIOS), chronic inflammation of the GI tract and antibiotic usage, as well as other less frequent causes of nausea, such as eosinophilic esophagitis. Given the relatively high occurrence of SA from sputum in the CF population, the high occurrence of enterotoxin producers within these SA isolates, combined with the frequent reporting of nausea, we are now exploring if this could be contributing to nausea in our CF patient population. Further work is now required to determine the stability of SA enterotoxins produced in the CF lung, particularly their persistence against denaturation by the proteolytic environment within the lung, including their intact passage from the lungs into the GI tract.