Common oligosaccharide moieties inhibit the adherence of typical and atypical respiratory pathogens.
Intervention in bacterial adhesion to host cells is a novel method of overcoming current problems associated with antibiotic resistance. Antibiotic-resistant strains of bacteria that cause respiratory tract infections are a problem in hospitals and could be used in bioterrorist attacks. A range of bacterial species was demonstrated to attach to an alveolar epithelial (A549) cell line. In all cases, cell surface oligosaccharides were important in attachment, demonstrated by reduced adhesion when A549 cells were pre-treated with tunicamycin. Bacillus anthracis and Yersinia pestis displayed a restricted tropism for oligosaccharides compared to the environmental, opportunistic pathogens, Pseudomonas aeruginosa, Burkholderia cenocepacia, Burkholderia pseudomallei and Legionella pneumophila. The compound with the greatest anti-adhesion activity was p-nitrophenol. Other generic attachment inhibitors included the polymeric saccharides (dextran and heparin), GalNAcbeta1-4Gal, GalNAcbeta1-3Gal, Galbeta1-4GlcNAc and Galbeta1-3GlcNAc. Burkholderia pseudomallei attachment was particularly susceptible to oligosaccharide inhibition. Combinations of such compounds may serve as a novel generic therapeutics for respiratory tract infections.
Thomas
Richard
R
Defence Science & Technology Laboratories (Dstl), Biomedical Sciences, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK 2Health Protection Agency (HPA), Porton Down, Salisbury, Wiltshire SP4 0JG, UK.
Brooks
Tim
T
Defence Science & Technology Laboratories (Dstl), Biomedical Sciences, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK 2Health Protection Agency (HPA), Porton Down, Salisbury, Wiltshire SP4 0JG, UK.
D001419:Bacteria / Q000472:pathogenicity*; D001422:Bacterial Adhesion / Q000187:drug effects*; D016957:Burkholderia pseudomallei / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D004847:Epithelial Cells / Q000382:microbiology; D006801:Humans; D009844:Oligosaccharides / Q000494:pharmacology*; D011650:Pulmonary Alveoli / Q000382:microbiology*; D012141:Respiratory Tract Infections / Q000382:microbiology*
D009844:Oligosaccharides