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Category: Microbial Genetics and Molecular Biology; Bacterial Pathogenesis
Genes for the Filamentous Hemagglutinin and Fimbriae of Bordetella pertussis: Colocation, Coregulation, and Cooperation?, Page 1 of 2
< Previous page | Next page > /docserver/preview/fulltext/10.1128/9781555818340/9781555810825_Chap10-1.gif /docserver/preview/fulltext/10.1128/9781555818340/9781555810825_Chap10-2.gifAbstract:
There is now evidence to show that filamentous hemagglutinin (FHA) and fimbriae act synergistically, a phenomenon which is reflected in the organization and regulation of their genes. Bordetella pertussis fimbriae have larger diameters (5 nm) and are much longer (up to several hundred nanometers long) than FHA. Three major fimbrial subunit genes, fim2, fim3, and fimX, have been identified in B. pertussis and are scattered around the chromosome. The fim2 and fim3 genes code for the serotype 2 and 3 fimbriae, respectively, while fimX is probably not expressed in most B. pertussis strains because of a deletion in its promoter region. Information about the function of FHA and fimbriae has also been obtained by studying mutants in animal models. Interestingly, the mutant strain was not affected in its ability to colonize the nasopharynx or lungs. The fact that both fimbrial and FHA mutants are affected in their ability to persist in the trachea suggests that fimbriae and FHA may cooperate not only in adherence to and invasion of macrophages but also in colonization of the trachea. There is evidence that other virulence factors also cooperate with FHA. Like fimbriae, pertussis toxin may facilitate the uptake of B. pertussis into macrophages by upregulating the CR3 receptor. Also, it has been proposed that pertactin and FHA interact with each other and that binding to some eukaryotic receptors requires this interaction.
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Organization and function of bvg, fha, and fim genes. Genes are represented by boxes, and arrowed lines indicate transcriptional units. The bvgA and bvgS genes code for a two-component sensory transduction system which translates environmental signals into transcriptional control of the fha and fim genes. BvgA is a positive regulator which binds to the promoter regions of the fha and fim genes. The fhaB gene codes for a large precursor molecule, which is transported across the inner (IM) and outer membrane (OM), after which it remains attached to the cell surface by means of its C-terminal region. This region is cleaved, and the resulting molecule (FHA) may be released from the cell or remain loosely associated with it. The fhaC gene codes for a protein which is required to transport FhaB across the outer membrane. The fimA gene probably represents the ancestral major fimbrial subunit gene. It contains a large deletion and is therefore inactive. The fimB gene codes for a periplasmic chaperon, which associates with fimbrial subunits to prevent nonproductive polymerization. The fimC gene codes for the anchorage protein, which is involved in the transport, assembly, and anchorage of fimbrial subunits. The fimD gene codes for the minor fimbrial subunit, which has been tentatively placed at the tip of the fimbrial structure. The fim2, fim3, and fimX genes code for the major fimbrial subunits and probably arose by duplication of fimA. The fimX gene is not expressed because of an inactive promoter.
Organization and function of bvg, fha, and fim genes. Genes are represented by boxes, and arrowed lines indicate transcriptional units. The bvgA and bvgS genes code for a two-component sensory transduction system which translates environmental signals into transcriptional control of the fha and fim genes. BvgA is a positive regulator which binds to the promoter regions of the fha and fim genes. The fhaB gene codes for a large precursor molecule, which is transported across the inner (IM) and outer membrane (OM), after which it remains attached to the cell surface by means of its C-terminal region. This region is cleaved, and the resulting molecule (FHA) may be released from the cell or remain loosely associated with it. The fhaC gene codes for a protein which is required to transport FhaB across the outer membrane. The fimA gene probably represents the ancestral major fimbrial subunit gene. It contains a large deletion and is therefore inactive. The fimB gene codes for a periplasmic chaperon, which associates with fimbrial subunits to prevent nonproductive polymerization. The fimC gene codes for the anchorage protein, which is involved in the transport, assembly, and anchorage of fimbrial subunits. The fimD gene codes for the minor fimbrial subunit, which has been tentatively placed at the tip of the fimbrial structure. The fim2, fim3, and fimX genes code for the major fimbrial subunits and probably arose by duplication of fimA. The fimX gene is not expressed because of an inactive promoter.
Nucleotide sequence similarities in the promoter region of bvg-activated genes. The fhaB sequence shown to bind to BvgA is overlined. Dots indicate sequence identities with the fhaB promoter region. Dashes refer to gaps introduced to increase the number of matches. The numbers refer to the distance to the initiation codons. The sequences of the following genes were obtained from previous reports: fhaB ( 30 ), fim3 ( 21 ), bvg ( 30 ), and fimB ( 48 ).
Nucleotide sequence similarities in the promoter region of bvg-activated genes. The fhaB sequence shown to bind to BvgA is overlined. Dots indicate sequence identities with the fhaB promoter region. Dashes refer to gaps introduced to increase the number of matches. The numbers refer to the distance to the initiation codons. The sequences of the following genes were obtained from previous reports: fhaB ( 30 ), fim3 ( 21 ), bvg ( 30 ), and fimB ( 48 ).
Binding features of the FHA molecule a
a See text for references.
b Numbers refer to the positions of the amino acid residues in FhaB.
Binding features of the FHA molecule a
a See text for references.
b Numbers refer to the positions of the amino acid residues in FhaB.