Analysis of Bacterial Phosphorylcholine-Related Genes Reveals an Association between Type-Specific Biosynthesis Pathways and Biomolecules Targeted for Phosphorylcholine Modification

Zhang, Yuan; Jen, Freda E.-C.; Edwards, Jennifer; Jennings, Michael P.

doi:10.1128/spectrum.01583-23

Cited by 2 publications

(2 citation statements)

References 87 publications

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“…While these bacteria are distantly related at the evolutionary scale, they are all covered by variable serotypes of polysaccharide capsules. Moreover, phosphocholine (PC) derivatives are found in the cell wall teichoic acid or C polysaccharide of S. pneumoniae 6 , lipopolysaccharide of H. influenzae 7 , and pilus of N. meningitidis 8 . It is completely unknown why the spleen is particularly important for host resistance to these bacteria.…”

Section: Introductionmentioning

confidence: 99%

Splenic red pulp macrophages eliminate the liver-resistantStreptococcus pneumoniaeduring bloodstream infection

Huang,

Zhao,

et al. 2024

Preprint

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The spleen is well-known for defense against invasive infections of encapsulated bacteria, particularly Streptococcus pneumoniae (pneumococcus). However, the precise mechanism of the splenic anti-bacterial immunity remains elusive. Here we report that red pulp (RP) macrophages execute the splenic defense against S. pneumoniae in mice, with the help of natural antibodies (nAbs) and complement system. The spleen slowly but substantially cleared encapsulated pneumococci from the bloodstream in the early phase of blood infection, especially the serotypes that resist to liver filtration. Among splenic macrophage subpopulations, only the lack of RP macrophages led to the complete loss of the splenic immunity. Intravital microscopy detected direct capture and phagocytic killing of circulating pneumococci by RP macrophages in the absence of neutrophils and inflammatory monocytes. Likewise, plasma nAbs targeting pneumococcal cell wall phosphocholine and complement protein C3 were essential for RP macrophage-mediated immune clearance. Our findings have thus uncovered the long-sought immune pathway against invasive pneumococcal infections in the spleen.

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Section: Introductionmentioning

confidence: 99%

Splenic red pulp macrophages eliminate the liver-resistantStreptococcus pneumoniaeduring bloodstream infection

Huang,

Zhao,

et al. 2024

Preprint

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“…Previous studies exploring IgA reactivity have predominantly used polyclonal IgA from mucosal secretions or fecal samples, posing challenges in confirming the IgA polyreactivity at the monoclonal level [ 19 , 25 , 29 ]. Phosphorylcholine (PC), a well-known molecule present in both gram-positive and gram-negative bacteria [ 34 , 35 ], has been extensively studied for its immunogenicity and pathogenicity. PC, employed as a T cell–independent antigen, has been the focus of studies developing vaccines against respiratory infections caused by PC-abundant Streptococcus pneumoniae [ 11 , 27 ].…”

mentioning

confidence: 99%

Broad specificity of monoclonal IgA (TEPC15-IgA) for enteric bacteria via phosphorylcholine-mediated interaction

KOYAMA,

ITO,

USAMI

et al. 2024

The Journal of Veterinary Medical Science

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Immunoglobulin A (IgA) is notable for its broad specificity toward multiple bacteria. Phosphorylcholine (PC) plays a role in the infection of pathogenic bacteria carrying PC and in the induction of IgA responses in the host immune system. The commercially available mouse monoclonal IgA, TEPC15-IgA, is a distinctive antibody with specificity for PC, warranting further exploration of its response to PC-bearing enteric bacteria. In this study, using 17 different enteric bacteria, including 3 aerobic and 14 anerobic bacteria that could be cultured in vitro, we confirmed that TEPC15-IgA recognizes 4 bacterial species: Lactobacillus taiwanensis, Limosilactobacillus frumenti, Streptococcus infantis, and Escherichia coli, although reactivity varied. Interestingly, TEPC15-IgA did not react with four of six Lactobacillus species used. Moreover, distinct target molecules associated with PC in L. taiwanensis and L. frumenti were evident, differing in molecular weight. These findings suggest that the natural generation of PC-specific IgA could prevent PCmediated infections and potentially facilitate the formation of a microflora rich in indigenous bacteria with PC, particularly in the gastrointestinal tract.

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Analysis of Bacterial Phosphorylcholine-Related Genes Reveals an Association between Type-Specific Biosynthesis Pathways and Biomolecules Targeted for Phosphorylcholine Modification

Abstract: The modification of bacterial surface virulence factors with phosphorylcholine (ChoP) plays an important role in bacterial virulence and pathogenesis. However, the ChoP biosynthetic pathways in bacteria have not been fully understood.

Cited by 2 publications

References 87 publications

Splenic red pulp macrophages eliminate the liver-resistantStreptococcus pneumoniaeduring bloodstream infection

Splenic red pulp macrophages eliminate the liver-resistantStreptococcus pneumoniaeduring bloodstream infection

Broad specificity of monoclonal IgA (TEPC15-IgA) for enteric bacteria via phosphorylcholine-mediated interaction

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