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Chapter 6 : Diversification of Receptor Specificities and Its Biological Consequences

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Diversification of Receptor Specificities and Its Biological Consequences, Page 1 of 2

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Abstract:

This chapter discusses concept and presents examples of the various mechanisms for receptor specificity diversification. The best-known examples of this type of variation are the pathogenicity islands (PAIs), which carry genes that encode adhesins with distinct receptor specificity, as well as genes that confer other specific aspects of pathogenicity. The changes in receptor specificity emerging from either acquisition or deletion of PAIs are usually much more pronounced than with allelic variation. The organisms express at least two families of adhesins, each of which can vary in its receptor specificity. The mechanism that controls the variation of the pilus shaft is gene rearrangement. Genomic DNA encodes one complete pilin gene and multiple copies of incomplete pilin genes. To better understand the biological consequences of the rapid change in receptor specificity, the chapter addresses how changes in two major adhesins expressed by , type 1 and P fimbrial bacterial adhesins, affect host and tissue tropism of the organism. The intraspecies diversities in the receptor specificities of FimH and PapG are due to allelic variations in the fimH and papG genes. In conclusion, the remarkable diversity in the fine sugar specificity of the type 1 and P fimbrial lectins clearly illustrates the concept that functional diversity of fimbrial lectins plays an important role in host tropism, tissue tropism, and infectivity.

Citation: Ofek I, Hasty D, Doyle R. 2003. Diversification of Receptor Specificities and Its Biological Consequences, p 101-112. In Bacterial Adhesion to Animal Cells and Tissues. ASM Press, Washington, DC. doi: 10.1128/9781555817800.ch6

Key Concept Ranking

Type 1 Fimbriae
0.71861595
Type IV Pili
0.7092018
Heparan Sulfate Proteoglycans
0.4395369
0.71861595
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Figures

Image of FIGURE 6.1
FIGURE 6.1

Hypothetical model of pilus biogenesis. OM and CM indicate the outer and inner (cytoplasmic) membranes, respectively. The pre-PilE molecules initially float in the CM. They consist of a globular domain (shaded oval) on the periplasmic face of the CM, a transmembrane domain (black), and a positively charged signal sequence (gray). After processing by the pre-PilE signal peptidase (PilD), the PilE subunits associate via their hydrophobic stems to form a pilus. The core of the pilus, therefore, forms a continuous hydrophobic layer with the CM. The hydrophobic continuum facilitates polymerization and depolymerization of pili under control of the CM-associated polymerization center (PilDFGT, etc.). Alternative cleavage of pre- PilE at Ala40 leads to release of S-pilin (soluble subunits). Signal peptidase 1 (SP1) is thought to be responsible for S-pilin production. The assembled pili, and presumably also S-pilin, penetrate the OM through a pore formed by the multisubunit complex of Omc. PilC facilitates the penetration of pili through the pore and sticks to the pilus tip, where it acts as a human cell-specific adhesin. (Reprinted from reference with permission from the publisher.)

Citation: Ofek I, Hasty D, Doyle R. 2003. Diversification of Receptor Specificities and Its Biological Consequences, p 101-112. In Bacterial Adhesion to Animal Cells and Tissues. ASM Press, Washington, DC. doi: 10.1128/9781555817800.ch6
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Image of FIGURE 6.2
FIGURE 6.2

Schematic diagram of pilus variation in The major subunit of the pilus shaft, PilE, is a member of the type IV pilus family. The extreme antigenic variability found in however, appears to be unique among the type IV-expressing genera. The chromosomal locus for pilus expression contains a complete (expressed) gene. The chromosome also contains, often in clusters, up to 15 (or more) (silent) genes, all lacking the invariant N-terminal domain. Homologous recombination between the variable domain of and a partial gene leads to structural variation of the PilE protein. Silent genes may also be present due to transformation of genetic information from other strains, offering another pathway for genetic exchange with the segment, leading to even more diversity. Because of the large number of partial sequences available and the additional possibilities for horizontal exchange, a single strain could theoretically yield daughters that express thousands of different PilE proteins. also usually possess two distinct genes for the tip adhesin PilC, and PilC appears to be essential for adhesion, but it is also clear that changes in PilE structure influence the adhesion behavior of piliated strains.

Citation: Ofek I, Hasty D, Doyle R. 2003. Diversification of Receptor Specificities and Its Biological Consequences, p 101-112. In Bacterial Adhesion to Animal Cells and Tissues. ASM Press, Washington, DC. doi: 10.1128/9781555817800.ch6
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Image of FIGURE 6.3
FIGURE 6.3

Phylogenetic analysis of FimH alleles. (A) Amino acid sequences of FimH variants. The alleles are listed based on an increasing Man1/Man3 binding ratio. The residues listed above the 11 alleles are the amino acid residues of the new alleles that vary from the original FimH sequence. Only polymorphic residues are shown, and the positions are numbered vertically from −16 of the leader peptide to +201 of the mature FimH. Δ indicates deleted residues. (B) Inferred phylogenetic network demonstrating evolutionary relationships of the FimH alleles shown in panel A. Each node represents a distinct FimH allele, numbered as in panel A. The allele labeled n represents a hypothetical FimH that differs from allele 2 by the substitution of Asp (N) for Tyr (T) in the leader sequence (residue −16) and phenotypically should be equivalent to allele 2. Internal nodes are shown in bold. The deduced sequences of the 11 FimH proteins exhibit greater than 99% homology, and the network showing their phylogenetic relationships is fully consistent, without any homoplasty. Branch lengths are scaled to the number of amino acids that differ between alleles. The deletion of 4 amino acids in FimH allele 10 is considered to be a single event, equivalent to one amino acid substitution. (Reprinted from reference with permission from the publisher.)

Citation: Ofek I, Hasty D, Doyle R. 2003. Diversification of Receptor Specificities and Its Biological Consequences, p 101-112. In Bacterial Adhesion to Animal Cells and Tissues. ASM Press, Washington, DC. doi: 10.1128/9781555817800.ch6
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Image of FIGURE 6.4
FIGURE 6.4

β-sheet topology diagram of the lectin (top) and pilin (bottom) domains of FimH (see reference for more details). Indicated on this diagram are variant amino acids which affect FimH function that were found either among naturally occurring isolates or in a random mutant library. Although the diagram is not precisely to scale, the relative positions of amino acids are indicated accurately. Residues indicated are those that caused enhanced monomannose binding (solid circles), those that caused complete loss of D-mannose binding (solid squares), and those that were neutral substitutions able to act in concert with other mutations to enhance monomannose binding (X's). The residues of the mannose binding site are also indicated (open circles). Interestingly, most of the residues that resulted in increased binding to monomannose units were found at the opposite end of the barrel-like lectin domain from the actual binding site. Furthermore, it is interesting that at least one residue in the pilin domain also affected the lectin binding activity, consistent with the notion that association of FimH with the main fimbrial shaft via its pilin domain affects the fine sugar specificity of the lectin domain (see the text). (Reprinted from reference with permission from the publisher.)

Citation: Ofek I, Hasty D, Doyle R. 2003. Diversification of Receptor Specificities and Its Biological Consequences, p 101-112. In Bacterial Adhesion to Animal Cells and Tissues. ASM Press, Washington, DC. doi: 10.1128/9781555817800.ch6
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References

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Tables

Generic image for table
TABLE 6.1

Major mechanisms for variation of receptor specificity of bacterial adhesins

Citation: Ofek I, Hasty D, Doyle R. 2003. Diversification of Receptor Specificities and Its Biological Consequences, p 101-112. In Bacterial Adhesion to Animal Cells and Tissues. ASM Press, Washington, DC. doi: 10.1128/9781555817800.ch6
Generic image for table
TABLE 6.2

Inter- and intraspecies diversity in the primary and fine sugar specificities of enterobacterial fimbrial lectins

Citation: Ofek I, Hasty D, Doyle R. 2003. Diversification of Receptor Specificities and Its Biological Consequences, p 101-112. In Bacterial Adhesion to Animal Cells and Tissues. ASM Press, Washington, DC. doi: 10.1128/9781555817800.ch6
Generic image for table
TABLE 6.3

Examples of PAIs encoding adhesins

Citation: Ofek I, Hasty D, Doyle R. 2003. Diversification of Receptor Specificities and Its Biological Consequences, p 101-112. In Bacterial Adhesion to Animal Cells and Tissues. ASM Press, Washington, DC. doi: 10.1128/9781555817800.ch6
Generic image for table
TABLE 6.4

Relationship between the fine receptor specificity and adhesion to cells from various tissues

Citation: Ofek I, Hasty D, Doyle R. 2003. Diversification of Receptor Specificities and Its Biological Consequences, p 101-112. In Bacterial Adhesion to Animal Cells and Tissues. ASM Press, Washington, DC. doi: 10.1128/9781555817800.ch6

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