Bacterial Polysaccharide A (PSA) & Bacteroides fragilis

What does to be instrumental for Bacteroides fragilis success as a commensal?

Production of Bacterial Polysaccharide A (PSA) by Bacteroides fragilis has been proposed to be instrumental for the bacterium’s success as a commensal (9). It is suggested that Bacterial Polysaccharide A (PSA), produced by Bacteroides fragilis, is an identified symbiont factor model for immunomodulation. Thus, PSA could be one of the potentially numerous bacterial cell components capable of promoting protective responses against neuroinflammation (1)

What immune effect does PSA (polysaccharide A) have on the host?

Bacterial Polysaccharide A (PSA) induces regulatory T cells (Tregs) and stimulates secretion of the anti-inflammatory cytokine Interleukin-10 (IL-10) (2, 3)

The Bacterial Polysaccharide A (PSA) from the capsule of Bacteroides fragilis is essential for balancing immune cell populations in the gut (4). It can induce MHC class II / HLA class II Human-dependent CD4+ T cell expansion; PSA was the first identified nonpeptide antigen capable of exerting this kind of response and revealing a role for polysaccharides as antigens (8).

Immunomodulatory activities of Bacterial Polysaccharide A (PSA) during Bacteroides fragilis colonization include correcting systemic T cell deficiencies and Th1/Th2 imbalances and directing lymphoid organogenesis (5)

Which components of Bacteroides fragilis play a significant role in the immune effects?

Bacteroides fragilis produces immunomodulatory capsular polysaccharides that stimulate the production of Anti-inflammatory cytokines and the conversion of CD4+ T cells into RAR-related Orphan Receptor Gamma/T (ROR-gamma/t) Isoform 2 (NR1F3)t + Foxp3 + Colonic Treg cells that produce IL-10 (2, 3, 5, 6)

How does Bacteroides fragilis modulate its surface polysaccharides?

Through phase-variable synthesis — the biosynthesis loci for seven of its eight capsular polysaccharides (PSA–PSH) contain invertible promoters that can switch orientation between "ON" and "OFF" relative to the downstream biosynthesis operon (7)

How many polysaccharides does Bacteroides fragilis produce, and how are they regulated?

Eight polysaccharides (PSA through PSH) are produced; seven of the eight are regulated by these invertible promoter switches (7)

What controls expression of these polysaccharides?

Reversible, DNA-inversion-based promoter switching — a form of phase variation — rather than fixed genetic expression (7)

Does PSA have a protective role in disease?

Yes — PSA confers protection against experimental colitis, based on multiple cited studies (2, 5, 11, 12). Polysaccharide A (PSA) from Bacteroides fragilis promotes normal immune homeostasis and protects against Experimental Colitis through the suppression of Interleukin-17 (IL-17) / IL-17A (mCTLA-8) Production (2, 10, 13, 14).

Why is PSA classified as "anti-inflammatory"?

Because of its combined effects: Treg induction, IL-10 secretion, and demonstrated protection in colitis models — together establishing its immunomodulatory, anti-inflammatory profile (2, 3, 5, 11)

Are there harmful effects of the capsular polysccharides?

If this bacterium translocates from the intestine to the peritoneum, then the capsular polysaccharides can cause inflammation, which results in the formation of an abscess (3, 15)

References

(1) Erturk-Hasdemir et al. 2021
(2) Mazmanian et al. 2008
(3) Surana & Kasper 2012 Immunol Rev. 245: 13–26
(4) Zheng et al. 2020c Cell Res. 30: 492-506
(5) Round & Mazmanian 2010
(6) Zeng & Chi 2015 Trends Immunol. 36: 3-12
(7) Krinos et al. 2001
(8) Johnson et al. 2015a Journal of Biological Chemistry 290: 5007-5014
(9) Hooper et al. 2012
(10) Mazmanian et al. 2005
(11) Dasgupta et al. 2014 Cell Host and Microbe. 15: 413-423
(12) Chang et al. 2017 PLoS One 12: e0180025
(13) Tzianabos et al. 1999 J Immunol. 163: 893–97
(14) Wang et al. 2006a J Exp Med. 203: 2853–63
(15) Browne et al. 2017

see also:
Bacterial Polysaccharide A (PSA) & Immunomodulation
Gut microbiota & Multiple sclerosis (MS)
MHC class II & Polysaccharide A (PSA)