Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0348321 (Haemophilus)
 15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The genes involved in Haemophilus influenzae type b capsule expression are present as a duplication of an approximately 18-kb DNA segment (the Cap b locus). It has been shown previously that recombination occurs between the two copies of the repeat, resulting in deletion of one copy and loss of capsule expression at frequencies of 0.1%-0.5%. The present study tested the hypothesis that the duplicated arrangement could serve as a template for further amplification of capsule gene sequences. Southern hybridization analysis of 66 type b invasive isolates showed that amplifications exist and are moderately common (23/66 were amplified). In addition to three copies of the 18-kb repeat, four copies were detected in some strains, and up to five copies in 1 isolate. By ELISA, a five-copy strain made about six times more capsular polysaccharide than did an isogenic two-copy derivative. The evolutionary significance of the duplicated arrangement may be its ability to rapidly amplify under conditions where it is advantageous to produce more capsule.
 ...
PMID:Genes involved in Haemophilus influenzae type b capsule expression are frequently amplified. 842 Nov 69

Amplification of the Cap b locus of Haemophilus influenzae occurs frequently in clinical isolates and has been proposed to be a mechanism by which this organism evades host defense. To determine if amplification of this locus affected complement fixation, in vitro studies to determine complement-mediated bacteriolysis and complement-mediated opsonization of an isogenic set of organisms containing 2, 3, and 4 copies of the Cap b locus were performed. Organisms containing 4 copies of the Cap b locus were significantly more resistant to antibody-dependent, classical complement pathway-directed bacteriolysis than were organisms containing 2 copies. Organisms containing 3 copies of this locus exhibited intermediate susceptibility to lysis. Complement-mediated opsonization of these organisms was assessed by determining the degree of binding of bacteria to murine or human macrophages or to nonphagocytic cells transfected with the genes for human Mac-1, the complement receptor type 3. In all three assay systems, organisms containing 4 copies of the Cap b locus bound less well than did organisms containing 2 copies of this locus. Consistent with their decreased susceptibility to lysis and opsonization, organisms with 4 copies of the Cap b locus fixed less C3 than did organisms containing 2 copies. These data demonstrate that amplification of the Cap b locus is associated with decreased susceptibility to complement-mediated lysis and decreased complement-mediated opsonization and suggest that amplification is used by these pathogens to increase their resistance to complement-dependent host defense mechanisms [correction of mecanisms].
 ...
PMID:Effect of amplification of the Cap b locus on complement-mediated bacteriolysis and opsonization of type b Haemophilus influenzae. 889 Feb 38