e-journal

Kdo2-lipid A: structural diversity and impact on immunopharmacology

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3-deoxy-d-manno-octulosonic acid-lipid A (Kdo2-lipid A) is the essential component of lipopolysaccharide in most Gram-negative bacteria and the minimal structural component to sustain bacterial viability. It serves as the active component of lipopolysaccharide to stimulate potent host immune responses through the complex of Toll-like-receptor 4 (TLR4) and myeloid differentiation protein 2. The entire biosynthetic pathway of Escherichia coli Kdo2-lipid A has been elucidated and the nine enzymes of the pathway are shared by most Gram-negative bacteria, indicating conserved Kdo2-lipid A structure across different species. Yet many bacteria can modify the structure of their Kdo2-lipid A which serves as a strategy to modulate bacterial virulence and adapt to different growth environments as well as to avoid recognition by the mammalian innate immune systems. Key enzymes and receptors involved in Kdo2-lipid A biosynthesis, structural modification and its interaction with the TLR4 pathway represent a clear opportunity for immunopharmacological exploitation. These include the development of novel antibiotics targeting key biosynthetic enzymes and utilization of structurally modified Kdo2-lipid A or correspondingly engineered live bacteria as vaccines and adjuvants. Kdo2-lipid A/TLR4 antagonists can also be applied in anti-inflammatory interventions. This review summarizes recent knowledge on both the fundamental processes of Kdo2-lipid A biosynthesis, structural modification and immune stimulation, and applied research on pharmacological exploitations of these processes for therapeutic development.
Key words: Kdo2 -lipid A, lipopolysaccharide, endotoxin, Gram-negative bacteria, outer membrane.

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Ketersediaan

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Informasi Detail

Judul Seri

Biological Reviews

No. Panggil

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Penerbit

U.K : John Wiley & Sons Ltd., 2015

Deskripsi Fisik

Biological Reviews 2015

Bahasa

English

ISBN/ISSN

doi: 10.1111/brv.121

Klasifikasi

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Tipe Isi

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Tipe Media

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Tipe Pembawa

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Edisi

(2015), 90, pp. 408–427.

Subjek

PSIKOLOGI

Info Detail Spesifik

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Pernyataan Tanggungjawab

Mutia/Agus

Versi lain/terkait

Lampiran Berkas

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