Xylitol may provide a new approach in cystic fibrosis (CF) therapy by preventing
the onset of bacterial infections. Researchers from the University of Iowa,
US, have found that xylitol, a sugar which is used in chewing gum, lozenges
and syrups, may enhance the innate antibacterial defence system at the airway
surface. Other research from the same university explains the mechanism of bacterial
biofilm formation in CF.
Dr Jospeh Zabner (associate professor of internal medicine) and colleagues explain
that there is a thin layer of airway surface liquid in the airways that contains
endogenous antimicrobial substances. An increase in salt concentration in this
liquid inhibits the activity of antimicrobial factors and some studies have
suggested that this increase in salt concentration may partially explain the
pathogenesis of CF.
The researchers tested the effect of xylitol on salt concentration in airway
surface liquid in in vitro experiments on human airway epithelia. The salt concentration
fell in both CF epithelium and non-CF epithelium. The initial salt concentration
in CF epithelium was approximately double that of non-CF epithelium but, following
xylitol application, the values fell to approximately normal levels. The researchers
examined the effect of xylitol on bacteria and found that it did not inhibit
endogenous antibiotics, have an antibiotic effect or serve as a carbon source
for bacterial growth. They suggest that, since xylitol had no antimicrobial
effect of its own and because it decreases salt concentrations in airway surface
liquid, its mechanism of action was to increase the activity of endogenous antimicrobial
factors.
They also conducted a randomised, double-blind, crossover study of 21 patients,
which showed that compared with saline, xylitol significantly reduced the number
of Staphylococcus on the nasal surface. The researchers comment that while xylitol
may be of value in preventing airway infection, it was unlikely that it would
have any use once an infection was established (Proceedings of the National
Academy of Sciences 2000;97:11614).
Bacterial biofilms
The reason that Pseudomonas aeruginosa infection cannot be eradicated once it
has colonised the lungs in CF patients may be because it exists in biofilms,
say Dr Pradeep Singh (department of internal medicine) and colleagues.
They examined sputum from CF patients with P aeruginosa infection and found
that the bacterium was present in clusters encased in a densely stained matrix.
This was consistent with the appearance of biofilms where bacterial cells were
encased in an extracellular polysaccharide matrix. In order to form biofilms,
bacteria secreted “quorum-sensing” agents above a certain threshold
which turned a disorganised colony into a more organised biofilm. The abundance
of two such agents differed in P aeruginosa in CF sputum compared with normal.
Quorum-sensing signals could be used to identify agents that interfere with
biofilm development, they suggest (Nature 2000;407:762).