Bacteroides
Dongyou Liu in Laboratory Models for Foodborne Infections, 2017
Histolytic enzymes, such as hyaluronidase and chondroitin sulfatase present in some B. fragilis, can attack the host’s extracellular matrix. Proteases of B. fragilis have also been implicated in destroying brush border enzymes acting on the microvillus membranes for the final digestion of food and absorption of nutrients. Other enzymes, hemolysins (HlyA and HlyB), and neuraminidase encoded by the nanH gene are also important. Neuraminidase is found in many pathogenic bacteria and is generally considered as a virulence factor; this enzyme catalyzes the removal of the sialic acid from epithelial cells and immunoactive proteins such as IgG. Several B. fragilis strains have neuraminidase activity, and it has been suggested that this activity plays a role in the bacterial attachment to animal cells and to the hemagglutination.5
Galactosialidosis
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop in Atlas of Inherited Metabolic Diseases, 2020
The molecular defect is in the lysosomal PPCA, the existence of which became evident through studies of patients with galactosialidosis [18, 61]. This protein is normally synthesized as a 54 kDa precursor, which is modified post-translationally to 32 and 20 kDa polypeptides which proved to be the corrective factor [13, 16, 62]. Immunoprecipitation demonstrated absence of the 54, 32, and 20 kDa polypeptides in fibroblasts of patients with galactosialidosis [16]. Neuraminidase aggregates normally with β-galactosidase and protective factor in a large multimer that resists proteolytic degradation [62–65]. Neuraminidase requires protective protein for activity. The multimer aggregate correctly routes the two glycosidases to the lysosome and protects them from rapid lysosomal proteolysis. The isolation of the cDNA for the protective protein [58] and its expression in COS cells [59, 65] elucidated the structure, function, and physiology of the protein. The sequence begins with a signal peptide that is cleaved, followed by 298 amino acids of the 32 kDa protein, which is followed by the 20 kDa protein; the two make up the 54 kDa precursor. The latter, synthesized in COS cells from the cDNA, is taken up by the fibroblasts of patients with galactosialidosis and restores activity in both enzymes [58].
Antiviral therapeutics for viral infections of the central nervous system
Avindra Nath, Joseph R. Berger in Clinical Neurovirology, 2020
Zanamivir and oseltamivir are structurally similar compounds that work by competitively binding neuraminidase, a surface glycoprotein that is common to both influenza A and B. Neuraminidase is essential for the release and spread of newly formed virus, making this enzyme an attractive target for inhibiting viral replication. Specifically, neuraminidase enables the release of the new viral particle from the host cell by cleaving the terminal sialic acid from glycoproteins on the cell surface. It also facilitates the migration of virus through mucous, allowing spread through the respiratory tract. Zanamivir is a synthetic competitive inhibitor, while oseltamivir is an ethyl ester prodrug that is converted to its active form by hepatic esterases. Both are administered orally and, therefore, are of limited value in the treatment of CNS disease.
Exploring the biomedical potential of a novel modified glass ionomer cement against the pandrug-resistant oral pathogen Candida albicans SYN-01
Published in Journal of Oral Microbiology, 2023
Nessma A. El Zawawy, Samy El-Safty, El-Refaie Kenawy, Sara Ibrahim Salem, Sameh S. Ali, Yehia A.-G. Mahmoud
Neuraminidase, or sialidase, is an exoglycosidase hydrolyzing α-linkage of the terminal sialic acids of various sialoglycoconjugates in diverse organisms, including viruses and microorganisms [31]. This enzyme modifies cell-surface-located sialoglycoconjugates, which play important roles in the regulation of cell-to-cell and cell-to-molecule interactions by mediating cell recognition or adhesion processes [32]. Neuraminidases are widely expressed as virulence factors by several mucosal pathogens [33]. Surprisingly, recent evidence suggests that neuraminidase activity may influence biofilm formation [34]. Although neuraminidase production of some microorganisms was considered the main virulence factor to cause infections, the mechanism of fungal neuraminidase in dental caries is not clearly defined [35,36]. Thus, our study may be, up to the moment, the first to provide an insight into the role of fungal neuraminidase enzyme in dental infections.
Mass spectrometry for the identification and analysis of highly complex glycosylation of therapeutic or pathogenic proteins
Published in Expert Review of Proteomics, 2020
Yukako Ohyama, Kazuki Nakajima, Matthew B. Renfrow, Jan Novak, Kazuo Takahashi
The influenza virus also uses protein glycosylation as a key component of its host-cell entry and immune evasion. Specifically, the surface proteins of the viral particles, hemagglutinin and neuraminidase, play vital roles in infection. The number of N-glycans in the hemagglutinin globular domain changes as it circulates in the human population. Although the N-glycans on hemagglutinin are not as densely clustered as those found on HIV-1 Env, they play a role in immune evasion by masking antigenic sites from antibodies (for review see [140]). However, soluble C-type lectins, such as the mannose-binding lectin and surfactant protein, are known to recognize influenza hemagglutinin glycans and promote innate immune responses by macrophages and other immune mechanisms [141,142]. Viral hemagglutinin protein binds sialic acid groups of cellular surface proteins to achieve viral attachment and entry. Human influenza viruses bind preferentially to α2,6-linked sialic acid, whereas avian influenza viruses use α2,3-linked sialic acid. Amino acids at key positions in the hemagglutinin receptor that affect binding specificity have been identified in the seasonal human and avian viruses [143]. The influenza neuraminidase is vital for viral entry into the respiratory tract to bypass the sialic acid-rich mucus proteins. Neuraminidase is also required for release of newly formed viral particles from the cell surface of host cells [144]. Thus, drugs that are structural mimics of sialic acid can inhibit the activity of influenza neuraminidase and represent a viable treatment option (for review see [145]).
The use of antiviral drugs in children
Published in Journal of Chemotherapy, 2022
Marco Antonio Motisi, Agnese Tamborino, Sara Parigi, Luisa Galli, Maurizio de Martino, Elena Chiappini
Neuraminidase promotes the release of the virion from the infected host cell. Neuraminidase inhibitors are active against influenza type A and B viruses. Zanamivir is approved by the EMA for inhalation by children over the age of five. The dose is similar to that indicated for adults: two 5 mg inhalations twice daily for five days. Oseltamivir is approved by the EMA from birth age, administered twice daily for five days. Both drugs are also approved for post-exposure prevention. A systematic review involving 74 studies carried out in 2012 showed a reduction in the duration of influenza symptoms, complication rates and mortality with zanamivir and oseltamivir [10]. This success and the presence of viral strains with neuraminidase mutations that may affect their binding to oseltamivir led to the subsequent development of two more drugs in this class: peramivir, which can be administered intravenously in a single dose and is approved by the EMA for treatment in children over the age of two but not for post-exposure prophylaxis, and laninamavir, which has been approved in Japan for use in adults and children since 2010 and can be administered by inhalation in a single dose. Laninamivir has also proven effective against oseltamivir-resistant virus strains in adults [11]. It is used by inhalation as a single dose (40 mg over the age of ten and 20 mg under the age of ten), and is also approved in Japan for post-exposure prophylaxis.
Related Knowledge Centers
- Genome
- Glycosidic Bond
- Virulence
- Epitope
- Influenza
- Glycoside Hydrolase
- Neuraminic Acid
- Viral Neuraminidase
- Sialidase-1
- Sialidase-2