Chapter 5 : Role of Phosphorylcholine in Respiratory Tract Colonization

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Role of Phosphorylcholine in Respiratory Tract Colonization, Page 1 of 2

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The majority of the homologous sequences were “housekeeping genes” that are widely distributed among both respiratory and nonrespiratory tract bacterial species. It appears that the expression of choline phosphate (ChoP) phosphorylcholine among respiratory tract organisms is an example of convergent evolution since ChoP is present on distinct bacterial structures in different species. An additional consideration is that in each of these species, ChoP is exposed on the bacterial cell surface, suggesting that it plays a role in host-bacterium interaction. The chapter focuses on phosphorylcholine expression. Exchanging the licD genes between the two strains with ChoP on different chain extensions was sufficient to switch its position. Therefore, in addition to the mechanism involving phase variation, structural rearrangements within the oligosaccharide have the potential to aid the evasion of an immune response targeting ChoP. The chapter also discusses the role of ChoP in the host-bacterium interaction and the advantages and disadvantages that expression of this host-like structure may confer on bacterial survival. A series of experiments examined whether bacteria are predominantly ChoP phase-on or phase-off during colonization and systemic infection. The efficacy of the human anti-ChoP IgG was assessed by using in vitro assays that correlate with protection against and infection. The surface expression of ChoP appears to be particularly common among species that colonize predominantly the upper respiratory tract. This allows for bacterial mimicry of the host cell surface since choline is a prominent feature of the host cell membrane.

Citation: Weiser J. 2005. Role of Phosphorylcholine in Respiratory Tract Colonization, p 61-72. In Nataro J, Cohen P, Mobley H, Weiser J (ed), Colonization of Mucosal Surfaces. ASM Press, Washington, DC. doi: 10.1128/9781555817619.ch5

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Humoral Immune Response
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Figure 1

Composite Western immunoblot with MAb TEPC-15, summarizing the common phosphorylcholine epitope on six species of mucosal pathogens and examples of variation in its expression. Lanes: 1 and 2, nontypeable strain H233 phase variants with ChoP and ChoP LPS, respectively; 3, strain R6 lipoteichoic acid; 4 and 5, phase variants of strain Jp-2 without and with ChoP LPS, respectively; 6 to 10, grown at 26.5, 30.0, 33.5, 37.0, and 39.5°C, respectively; 11, purified pilin; 12 to 14, piliated phase variants of strain MS11 without and with the ChoP-LPS. Reprinted from reference 58 with permission from Elsevier.

Citation: Weiser J. 2005. Role of Phosphorylcholine in Respiratory Tract Colonization, p 61-72. In Nataro J, Cohen P, Mobley H, Weiser J (ed), Colonization of Mucosal Surfaces. ASM Press, Washington, DC. doi: 10.1128/9781555817619.ch5
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Figure 2

Current model of the pathway for expression of ChoP in and its proposed interactions within the airway.

Citation: Weiser J. 2005. Role of Phosphorylcholine in Respiratory Tract Colonization, p 61-72. In Nataro J, Cohen P, Mobley H, Weiser J (ed), Colonization of Mucosal Surfaces. ASM Press, Washington, DC. doi: 10.1128/9781555817619.ch5
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Figure 3

When host cells are the sole source of choline, is able to acquire choline by a dependent mechanism. (A) Time course of expression of ChoP on the LPS in bacteria adherent to D562 cells. Strains Rd (ChoP) and Rd:: (ChoP) were allowed to adhere to host epithelial cells in a medium lacking free choline for the period indicted, and the presence of ChoP on the LPS was detected by Western blotting of whole-cell lysates using MAb TEPC-15 to ChoP. (B) GlpQ is required for to transfer choline from host epithelial cells. D562 cells were grown in medium containing [H]choline and infected with the strain indicated (or control without bacteria) for 4 h, and incorporation of the radiolabel was detected in the bacterial fraction as the mean of counts per minute per well ± standard deviation ( 3). Panels A and B reprinted from reference 11 with permission from Blackwell Publishing.

Citation: Weiser J. 2005. Role of Phosphorylcholine in Respiratory Tract Colonization, p 61-72. In Nataro J, Cohen P, Mobley H, Weiser J (ed), Colonization of Mucosal Surfaces. ASM Press, Washington, DC. doi: 10.1128/9781555817619.ch5
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Figure 4

Effect of an rPAF antagonist (PAF-Ra) on bacterial adherence. Adherence of nontypeable or to Detroit 562 pharyngeal epithelial cells in the presence or absence of 1 µM PAF-Ra [1-O-hexadecyl-2-acetyl--glycerol-3-phospho-(-trimethyl)hexanolamine] is expressed as a percentage of the inoculum binding to epithelial cells after 60 min and values represent the means of at least three determinations in duplicate. Error bars indicate standard deviation. Asterisks indicate 0.05 compared to first bar in each panel.

Citation: Weiser J. 2005. Role of Phosphorylcholine in Respiratory Tract Colonization, p 61-72. In Nataro J, Cohen P, Mobley H, Weiser J (ed), Colonization of Mucosal Surfaces. ASM Press, Washington, DC. doi: 10.1128/9781555817619.ch5
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Table 1

Bacteria expressing the ChoP antigen/structure

Citation: Weiser J. 2005. Role of Phosphorylcholine in Respiratory Tract Colonization, p 61-72. In Nataro J, Cohen P, Mobley H, Weiser J (ed), Colonization of Mucosal Surfaces. ASM Press, Washington, DC. doi: 10.1128/9781555817619.ch5

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