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Pseudomonas aeruginosa II lectin stops human ciliary beating: therapeutic implications of fucose
E C Adam1, B S Mitchell, D U Schumacher
1Department of Human Morphology, University of Southampton, United Kingdom.
Abstract:
Respiratory tract infection by Pseudomomas aeruginosa may be life-threatening for intensive care patients and patients with cystic fibrosis (CF). The colonization of airways can be facilitated by bacterial lectins (carbohydrate-binding proteins) that attach bacteria to the glycoconjugates of the mucosa. We show in this paper that the fucose-specific lectin P. aeruginosa agglutinin II (PAII) produced by these bacteria can, in addition to facilitating bacterial adhesion, arrest ciliary beating in human airways in vitro. This inhibitory effect of the lectin can be abolished by preincubating PAII with its specific sugar, fucose. Furthermore, ciliary beating is completely restored by addition of fucose 2 h after administration of PAII to cell cultures. Therefore, adding a simple monosaccharide to nebulizers may improve the management of P. aeruginosa infection by abrogating the effect of PAII on ciliary beating, thus restoring part of the nonspecific pulmonary defense mechanisms of the airways.
Insights
Pseudomonas aeruginosa lectin PAII halts airway ciliary beating, a key defense against respiratory tract infections. Fucose, a simple sugar, can block PAII
Area of Science:
- Microbiology
- Pulmonology
- Biochemistry
Background:
- Pseudomonas aeruginosa poses a severe threat to intensive care and cystic fibrosis patients.
- Bacterial lectins mediate airway colonization by binding to mucosal glycoconjugates.
- Understanding lectin-host interactions is crucial for developing new therapeutic strategies.
Purpose of the Study:
- To investigate the role of the fucose-specific lectin PAII from P. aeruginosa in respiratory tract infections.
- To determine the effect of PAII on human airway ciliary beating.
- To explore the potential of fucose as an antagonist to PAII's inhibitory effects.
Main Methods:
- In vitro studies using human airway cell cultures.
- Assessing the impact of purified PAII on ciliary beating.
- Evaluating the inhibitory and restorative effects of fucose on PAII-mediated ciliary dysfunction.
Main Results:
- P. aeruginosa agglutinin II (PAII) was shown to arrest ciliary beating in human airway cells.
- Pre-incubation of PAII with fucose abolished its inhibitory effect on ciliary beating.
- Addition of fucose restored ciliary beating even after PAII administration.
Conclusions:
- PAII contributes to P. aeruginosa pathogenesis by inhibiting airway ciliary function.
- Fucose can effectively counteract the detrimental effects of PAII on cilia.
- Nebulized fucose may represent a novel therapeutic approach to manage P. aeruginosa airway infections.