Capsular type-specific polysaccharide partially inhibits group B Streptococcus-induced pulmonary hypertension.
Capsular type-specific polysaccharide is thought to be an important pathogenetic factor in Group B streptococcus (GBS) sepsis. To determine the effects of capsular type-specific polysaccharide on GBS-induced hemodynamic responses, anesthetized infant piglets were infused for 3 h with three related GBS Type lb strains that express different amounts of capsular type-specific polysaccharide. A larger capsule strain and a smaller capsule strain were isolated from an infected infant and its mother, respectively. A capsule-deficient mutant was then made from the larger capsule strain by transposon insertion mutagenesis. The smaller capsule strain and capsule-deficient mutant caused similar elevations in mean pulmonary artery pressure and pulmonary vascular resistance index and reductions in cardiac index. The larger capsule strain caused moderate pulmonary hypertension, but this response was smaller than for the other two GBS strains. Further comparisons in responses between the large capsule strain and its capsule-deficient mutant were then performed using unanesthetized piglets. The mutant caused significantly greater pulmonary hypertension and arterial plasma thromboxane B2 levels than the large capsule strain. The pulmonary hypertension induced by both strains was reversed by dazmegrel, a thromboxane A2 synthase inhibitor. These results suggest that (1) capsular type-specific polysaccharide is not an essential component in the generation of acute hemodynamic responses; (2) expression of large amounts of capsular type-specific polysaccharide on the organism surface partially inhibits GBS-induced pulmonary hypertension; and (3) the inhibition of the pulmonary responses is due to reduced thromboxane A2 release.(ABSTRACT TRUNCATED AT 250 WORDS)
Li
J X
JX
Department of Pediatrics, University of Alabama, Birmingham 35233-7335.
Gray
B M
BM
Pritchard
D G
DG
Oliver
J R
JR
Grantham
K D
KD
Philips
J B
JB
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D016667:Bacterial Capsules / Q000633:toxicity*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006439:Hemodynamics / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000097:blood / Q000188:drug therapy / Q000453:epidemiology / Q000209:etiology* / Q000503:physiopathology; D007093:Imidazoles / Q000627:therapeutic use; D011135:Polysaccharides, Bacterial / Q000633:toxicity*; D013290:Streptococcal Infections / Q000097:blood / Q000188:drug therapy / Q000453:epidemiology / Q000209:etiology* / Q000503:physiopathology; D013292:Streptococcus agalactiae / Q000187:drug effects* / Q000302:isolation & purification / Q000472:pathogenicity*; D013552:Swine; D013929:Thromboxane B2 / Q000097:blood; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D007093:Imidazoles; D011135:Polysaccharides, Bacterial; C039242:dazmegrel; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D013930:Thromboxane-A Synthase