title: Interaction of pneumolysin-sufficient and -deficient isogenic variants of Streptococcus pneumoniae with human respiratory mucosa.
abstract: Streptococcus pneumoniae is the most common cause of community-acquired pneumonia, and pneumolysin, a hemolytic toxin, is thought to be an important virulence factor. We have studied the interaction of a pneumolysin-sufficient type II S. pneumoniae strain (PL+) and an otherwise identical pneumolysin-deficient derivative (PL-) with human respiratory mucosa in an organ culture with an air interface for up to 48 h. Ciliary beat frequency (CBF) was measured by a photometric technique, and adherence to and invasion of the epithelium were assessed by scanning and transmission electron microscopy. PL+ and PL- caused a progressive fall in CBF compared with the control which became significant (P < 0.01) at 24 h for PL+ and at 48 h for PL-. At 24 h, there was a significant increase in the percentage of the mucosa of the organ culture that was damaged for PL+ compared with the control (P < 0.01) and PL- (P < 0.02). At 48 h, there was a significant increase in mucosal damage for both PL+ (P < 0.005) and PL- (P < 0.05) compared with the control. At 24 and 48 h, PL+ and PL- adhered predominantly to mucus and damaged cells. PL+ infection alone caused separation of tight junctions between epithelial cells, and at 48 h PL+ cells were adherent to the separated edges of otherwise healthy unciliated cells. PL+ and PL- both caused damage to the epithelial cell ultrastructure. S. pneumoniae infection caused patchy damage to the respiratory mucosa and a lowered CBF. These changes were more severe and occurred earlier with the pneumolysin-sufficient variant.
authors: Host Defence Unit, Royal Brompton National Heart and Lung Institute, London, United Kingdom.
authors: C F
authors: CF
authors: Rayner
authors: A D
authors: AD
authors: Jackson
authors: A
authors: A
authors: Rutman
authors: A
authors: A
authors: Dewar
authors: T J
authors: TJ
authors: Mitchell
authors: P W
authors: PW
authors: Andrew
authors: P J
authors: PJ
authors: Cole
authors: R
authors: R
authors: Wilson
mesh_terms: D000234:Adenoids / Q000382:microbiology*; D001422:Bacterial Adhesion; D001426:Bacterial Proteins; D002923:Cilia / Q000648:ultrastructure; D008855:Microscopy, Electron, Scanning; D009092:Mucous Membrane / Q000382:microbiology; D009093:Mucus; D009924:Organ Culture Techniques; D013296:Streptococcus pneumoniae / Q000472:pathogenicity*; D013301:Streptolysins / Q000172:deficiency / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; D013301:Streptolysins; C032290:plY protein, Streptococcus pneumoniae