e-journal

Structural engineering of a phage lysin that targets Gram-negative pathogens

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Bacterial pathogens are becoming increasingly resistant to antibiotics. As an alternative therapeutic strategy, phage therapy reagents containing purified viral lysins have been developed against Grampositive organisms but not against Gram-negative organisms due to the inability of these types of drugs to cross the bacterial outer membrane. We solved the crystal structures of a Yersinia pestis outer membrane transporter called FyuA and a bacterial toxin called pesticin that targets this transporter. FyuA is a β-barrel membrane protein belonging to the family of TonB dependent transporters,whereas pesticin is a soluble protein with two domains, one that binds to FyuA and another that is structurally similar to phage T4 lysozyme. The structure of pesticin allowed us to design a phage therapy reagent comprised of the FyuA binding domain of pesticin fused to the N-terminus of T4 lysozyme. This hybrid toxin kills
specific Yersinia and pathogenic E. coli strains and, importantly, can e the pesticin immunity protein (Pim) giving it a distinct advantage over pesticin. Furthermore, because FyuA is required for virulence and is more common in pathogenic bacteria, the hybrid toxin also has the advantage of targeting primarily disease-causing bacteria
rather than indiscriminately eliminating natural gut flora.

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Ketersediaan

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Informasi Detail

Judul Seri

PNAS

No. Panggil

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Penerbit

: ., 2012

Deskripsi Fisik

PNAS ∣ June 19, 2012 ∣ vol. 109 ∣ no. 25 ∣ 9857–9862

Bahasa

English

ISBN/ISSN

doi/10.1073/pnas.120

Klasifikasi

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Tipe Isi

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Tipe Media

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Tipe Pembawa

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Edisi

June 19, 2012 ∣ vol. 109 ∣ no. 25

Subjek

KESEHATAN

Info Detail Spesifik

-

Pernyataan Tanggungjawab

Wati/Agus

Versi lain/terkait

Lampiran Berkas

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