Effect of Pseudomonas aeruginosa rhamnolipids on mucociliary transport and ciliary beating

Abstract

Pseudomonas aeruginosa rhamnolipid causes ciliostasis and cell membrane damage to rabbit tissue, is a secretagogue in cats, and inhibits epithelial ion transport in sheep tissue. It could therefore perturb mucociliary clearance. We have investigated the effect of rhamnolipid on mucociliary transport in the anesthetized guinea pig and guinea pig and human respiratory epithelium in vitro. Application of rhamnolipid to the guinea pig tracheal mucosa reduced tracheal mucus velocity (TMV) in vivo in a dose-dependent manner: a 10-microgram bolus caused cessation of TMV without recovery; a 5-micrograms bolus reduced TMV over a period of 2 h by 22.6% (P = 0.037); a 2.5-microgram bolus caused no overall changes in TMV. The ultrastructure of guinea pig tracheal epithelium exposed to 10 micrograms of rhamnolipid in vivo was normal. Application of 1,000 micrograms/ml rhamnolipid had no effect on the ciliary beat frequency (CBF) of guinea pig tracheal rings in vitro after 30 min, but 250 micrograms/ml stopped ciliary beating after 3 h. Treatment with 100 micrograms/ml rhamnolipid caused immediate slowing of the CBF (P less than 0.01) of human nasal brushings (n = 7), which was maintained for 4 h. Mono- and dirhamnolipid had equivalent effects. The CBF of human nasal turbinate organ culture was also slowed by 100 micrograms/ml rhamnolipid, but only after 4 h (CBF test, 9.87 +/- 0.41 Hz; control, 11.48 +/- 0.27 Hz; P less than 0.05, n = 6), and there was subsequent recovery by 14 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Rhamnolipids, Microbial Virulence Factors, in Alzheimer’s Disease

“…The presence of RLs (up to 8 g/mL) in saliva specimens, yielded from cystic fibrosis patients, had been attributed to infection by P. aeruginosa, and denoted a direct relationship between the increased level of RLs and the clinical deterioration of the patient [68]. The RL amounts found in saliva specimens were much higher (as high as 65 g/mL) than these detected in secretions of a lung obtained from a cystic fibrosis patient [69].…”

“…The CSF samples were taken from different individuals than those who provided the serum samples. The average age of AD patients was 75 years (56-85), of MCI patients 70 years , and of controls 73.3 years (68)(69)(70)(71)(72)(73)(74)(75)(76)(77)(78)(79)(80)(81). Each sample was assayed in duplicate.…”

Development of an Antibody for Detection of Rhamnolipids Characterized as a Major Bacterial Virulence Factor

“…It was found that sputum samples obtained from P. aeruginosa-colonized Cystic fibrosis (CF) patients contained RLs (up to 8 μg/mL) and reported a correlation between elevated levels of RLs and worsened patient's clinical status [7]. These RL concentrations in sputum samples, however, might actually underestimate the concentrations present in the lower respiratory tract, as levels of 65 μg/mL were found in secretions of a lung removed from a CF patient [34]. Recently it was found that RL produced by different motile P. aeruginosa strains and clinical isolates from different sources including blood (PA strain 227 63 ± 10 μg/mL RL), skin (ranging approximately from 56, 538 and 702 μg/mL dependent from the strain PA-O, PA 264 and PA 1450 respectively), and Cystic fibrosis (CF) patients (795 ± 1 μg/mL of Rl from strain PA 391) [35].…”

The biology of bacterial colonization and invasion of the respiratory mucosa

“…Stimulate mucus production [8][9][10] Slow and disorganize ciliary beat [1,[11][12][13] Affect ion transport [14][15][16][17] Damage epithelium [1,11,13,[17][18][19]23] Enzymes that break down local immunoglobulin [24,25] Proteases cleave antibodies to create nonfunctional "blocking antibodies" IgA 1 proteases Exoproducts that alter immune effector cell function [24] Neutrophils: inhibit chemotaxis and phagocytosis, enhance oxidative metabolism Lymphocytes: impair cytokine production, activate suppressor T-cells Macrophages: reduce viability Bacterial adherence to epithelium [20][21][22] May be increased by environmental factors and in certain disease states Increased by epithelial damage Avoids clearance in secretions Enhances the effect of toxins released in the microenvironment of the epithelium Increases the availability of nutritional factors for bacterial growth Avoid immune surveillance [24,25,37,38] Antigenic heterogeneity of the bacterial surface Growth in biofilms Microcolonies of bacteria surround themselves with a polysaccharide gel Endocytosis, bacteria "hide" within epithelial cells …”