Safe as mother's milk: carbohydrates as future anti-adhesion drugs for bacterial diseases.
The majority of infectious diseases are initiated by adhesion of pathogenic organisms to the tissues of the host. In many cases, this adhesion is mediated by lectins present on the surface of the infectious organism that bind to complementary carbohydrates on the surface of the host tissues. Lectin-deficient mutants often lack ability to initiate infection. Soluble carbohydrates recognized by the bacterial lectins block the adhesion of the bacteria to animal cells in vitro. Moreover, they have also been shown to protect against experimental infection by lectin-carrying bacteria in different organs of mammals such as mice, rabbits, calves and monkeys. In a phase II clinical trial, a pentasaccharide shown to have anti-adhesive activity against Streptococcus pneumoniae and Hemophilus influenzae in vitro failed to protect young children from nasopharyngeal colonization with these organisms and from developing otitis media. This could be because insufficient drug was delivered via nasal spray, because bacteria express multiple specificities, the inhibition of which may require a cocktail of oligosaccharides, or because children have different carbohydrate receptors from those of adults. The results of a clinical trial in which N-acetylneuraminyl(alpha2-3)lactose was administered orally to Helicobacter pylori positive patients in an effort to reduce or eradicate bacterial colonization, are awaited with interest. Although the high cost of production of the required oligosaccharides is falling with the recent introduction of enzymatic methods of synthesis, new technologies, in particular the use of engineered bacteria, promise to lower it even further. Attachment of the oligosaccharides to soluble polymeric carriers will increase greatly their effectiveness as antiadhesion agents. There is no doubt that anti-adhesive oligosaccharides will in the near future join the arsenal of drugs for the therapy of bacterial diseases.
Sharon
N
N
Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel. bfsharon@weizmann.weizmann.ac.il
Ofek
I
I
D000328:Adult; D000818:Animals; D001422:Bacterial Adhesion / Q000187:drug effects* / Q000502:physiology; D001424:Bacterial Infections / Q000188:drug therapy*; D001665:Binding Sites; D002240:Carbohydrate Sequence; D002241:Carbohydrates / Q000494:pharmacology*; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D008969:Molecular Sequence Data
D002241:Carbohydrates