Selective Inhibition of Sialic Acid-Based Molecular Mimicry in Haemophilus influenzae Abrogates Serum Resistance

Heise, Torben; Langereis, Jeroen D.; Rossing, Emiel; Jonge, Marien I. de; Adema, Gosse J.; Büll, Christian; Boltje, Thomas J.

doi:10.1016/j.chembiol.2018.05.018

Cited by 27 publications

(59 citation statements)

References 30 publications

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“…A directed 11P6HΔsiaP gene deletion mutant was generated by allelic exchange of the target gene with a spectinomycin resistance cassette. Spectinomycin resistance cassettes with ϳ1,000-bp flanking sequences were amplified from the 86-028NPΔsiaP strain with primers R2866_0441_L1 (5=-TCAACAGAATTGACCGCACT-3=) and R2866_0441_R1 (5=-CTATGGCTTGGCAGGCTTAC-3=) (32). 11P6HΔsiaP gene deletion mutants were obtained by transformation of the PCR product by the method of Herriott et al (36) and selected by plating on sBHI agar plates containing 150 g/ml of spectinomycin.…”

Section: Methodsmentioning

confidence: 99%

Uptake of Sialic Acid by Nontypeable Haemophilus influenzae Increases Complement Resistance through Decreasing IgM-Dependent Complement Activation

et al. 2019

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Although nontypeable Haemophilus influenzae (NTHi) is a humanspecific nasopharyngeal commensal bacterium, it also causes upper respiratory tract infections in children and lower respiratory tract infections in the elderly, resulting in frequent antibiotic use. The transition from symbiotic colonizing bacterium to opportunistic pathogen is not completely understood. Incorporation of sialic acids into lipooligosaccharides is thought to play an important role in bacterial virulence. It has been known for more than 25 years that sialic acids increase resistance to complement-mediated killing; however, the mechanism of action has not been elucidated thus far. Here, we provide evidence that growth of NTHi in the presence of sialic acids Neu5Ac and Neu5Gc decreases complement-mediated killing through abrogating the classical pathway of complement activation by preventing mainly IgM antibody binding to the bacterial surface. Therefore, strategies that interfere with uptake or incorporation of sialic acids into the lipooligosaccharide, such as novel antibiotics and vaccines, might be worth exploring to prevent or treat NTHi infections.

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Section: Methodsmentioning

confidence: 99%

Uptake of Sialic Acid by Nontypeable Haemophilus influenzae Increases Complement Resistance through Decreasing IgM-Dependent Complement Activation

et al. 2019

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“…Another example is the non-typeable Haemophilus influenzae (NTHi), which is also able to take up sialic acids through a tripartite ATP-independent periplasmic (TRAP) transporter. Incorporation of the sialic acids in the NTHi membrane protects it from serum-mediated killing (97).…”

Section: Sialic Acids Used By Pathogens To Modulate Immunitymentioning

confidence: 99%

Modulation of Immune Tolerance via Siglec-Sialic Acid Interactions

2018

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One of the key features of the immune system is its extraordinary capacity to discriminate between self and non-self and to respond accordingly. Several molecular interactions allow the induction of acquired immune responses when a foreign antigen is recognized, while others regulate the resolution of inflammation, or the induction of tolerance to self-antigens. Post-translational signatures, such as glycans that are part of proteins (glycoproteins) and lipids (glycolipids) of host cells or pathogens, are increasingly appreciated as key molecules in regulating immunity vs. tolerance. Glycans are sensed by glycan binding receptors expressed on immune cells, such as C-type lectin receptors (CLRs) and Sialic acid binding immunoglobulin type lectins (Siglecs), that respond to specific glycan signatures by triggering tolerogenic or immunogenic signaling pathways. Glycan signatures present on healthy tissue, inflamed and malignant tissue or pathogens provide signals for “self” or “non-self” recognition. In this review we will focus on sialic acids that serve as “self” molecular pattern ligands for Siglecs. We will emphasize on the function of Siglec-expressing mononuclear phagocytes as sensors for sialic acids in tissue homeostasis and describe how the sialic acid-Siglec axis is exploited by tumors and pathogens for the induction of immune tolerance. Furthermore, we highlight how the sialic acid-Siglec axis can be utilized for clinical applications to induce or inhibit immune tolerance.

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“…In the immune system, sialoglycans such as sialyl Lewis x contribute to immune cell trafficking via binding to selectins on the endothelium (15), and they form the ligands for the immunomodulatory Siglec receptors that set the threshold for immune activation (16,17). Sialic acids also serve as binding sites for human pathogens and can be utilized by microorganisms for molecular mimicry (18,19). Furthermore, aberrant sialoglycan expression is associated with tumor growth, immune evasion, and metastasis (20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

Sialic acid O-acetylation: From biosynthesis to roles in health and disease

Visser

Moons

Timmermans

et al. 2021

Journal of Biological Chemistry

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

show abstract

Selective Inhibition of Sialic Acid-Based Molecular Mimicry in Haemophilus influenzae Abrogates Serum Resistance

Cited by 27 publications

References 30 publications

Uptake of Sialic Acid by Nontypeable Haemophilus influenzae Increases Complement Resistance through Decreasing IgM-Dependent Complement Activation

Uptake of Sialic Acid by Nontypeable Haemophilus influenzae Increases Complement Resistance through Decreasing IgM-Dependent Complement Activation

Modulation of Immune Tolerance via Siglec-Sialic Acid Interactions

Sialic acid O-acetylation: From biosynthesis to roles in health and disease

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