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Review
. 2022 Oct 20:13:1028796.
doi: 10.3389/fmicb.2022.1028796. eCollection 2022.

Biological functions of sialic acid as a component of bacterial endotoxin

Bartłomiej Dudek  1 , Jacek Rybka  2 , Gabriela Bugla-Płoskońska  1 , Agnieszka Korzeniowska-Kowal  2 , Bożena Futoma-Kołoch  1 , Aleksandra Pawlak  1 , Andrzej Gamian  2
Affiliations
Review

Biological functions of sialic acid as a component of bacterial endotoxin

Bartłomiej Dudek et al. Front Microbiol. .

Abstract

Lipopolysaccharide (endotoxin, LPS) is an important Gram-negative bacteria antigen. LPS of some bacteria contains sialic acid (Neu5Ac) as a component of O-antigen (O-Ag), in this review we present an overview of bacteria in which the presence of Neu5Ac has been confirmed in their outer envelope and the possible ways that bacteria can acquire Neu5Ac. We explain the role of Neu5Ac in bacterial pathogenesis, and also involvement of Neu5Ac in bacterial evading the host innate immunity response and molecular mimicry phenomenon. We also highlight the role of sialic acid in the mechanism of bacterial resistance to action of serum complement. Despite a number of studies on involvement of Neu5Ac in bacterial pathogenesis many aspects of this phenomenon are still not understood.

Keywords: Gram-negative bacteria; O-antigen; lipopolysaccharide; molecular mimicry; outer membrane; pathogenesis; sialic acid.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
(A) Schematic structure of LPS molecule: O-specific antigen chain has a variable length, thus the amount of sialic acid residues per LPS molecule can vary from none (in rough LPS) up to over one hundred (in so-called very-long-O-antigen LPS); (B) Chemical structures of most common members of neuraminic acids family: N-acetylneuraminic acid (Neu5Ac), 2-keto-3-deoxy-nonulosonic acid (Kdn), N-glycolylneuraminic acid (Neu5Gc), legionaminic acid (Leg), and pseudaminic acid (Pse), presented in simplified Fisher projection formula.
Figure 2
Figure 2
Structures of LPS containing Neu5Ac as a component of O-Ag.
Figure 3
Figure 3
Correlation between the presence of NeuAc in bacterial LPSs and complement activation. There are four possible ways of C activation depending on sialylated LPSs and outer membrane proteins. (A) The sialylated LOS of Haemophilus influenzae and Neisseria gonorrhoeae inhibits the activation of the alternative pathway (AP) of the complement system by binding of factor H. The binding of factor H requires the presence of gonococcal outer membrane protein PorB (Ram et al., 1998; Figueira et al., 2007; Madico et al., 2007). (B) Enterobacteriaceae such as Escherichia coli O104, E. coli O24, E. coli O56, Citrobacter braakii O37 and Salmonella O48 were killed via the AP pathway activation although they possessed sialylated LPSs (Bugla-Płoskońska and Doroszkiewicz, 2006; Bugla-Płoskońska et al., 2010a,b). (C) LPS with a low content (near the limit of detection) of sialic acid in LPS of Salmonella Isaszeg enabled C3 activation on OMPs in the range of molecular masses of 35–48 kDa (Futoma-Kołoch et al., 2015). (D) LPS with a high content of sialic acid of S. Ngozi and S. subsp. arizonae impeded C3 activation by OMPs in the range of molecular masses of 35–48 kDa (Futoma-Kołoch et al., 2015).
Figure 4
Figure 4
Pathways for deploying sialic acid on bacterial pathogens cell surface: Neisseria meningitidis, Neisseria gonorrhoeae (Shell et al., 2002; Lewis et al., 2015), Haemophilus influenzae (Jessamine and Ronald, 1990; Fox et al., 2006), Campylobacter jejuni (Chiu et al., 2007), Escherichia coli (Shen et al., 1999; Vimr et al., 2004; Severi et al., 2007). IM, inner membrane; PG, peptidoglycan; OM, outer membrane; LPS, lipopolysaccharide; CP, capsular polysaccharide.
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