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影响因子: 1.352 5年影响因子: 3.347 SJR: 1.022 SNIP: 0.55 CiteScore™: 2.19

ISSN 打印: 1040-8401
ISSN 在线: 2162-6472

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DOI: 10.1615/CritRevImmunol.v27.i3.40
pages 233-245

Rapid Clearance of Bacteria and Their Toxins: Development of Therapeutic Proteins

Meghan Kunkel
Biosciences Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA
Momchilo Vuyisich
Biosciences Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA
Gnana Gnanakaran
Theory Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA
George E. Bruening
Plant Pathology, UC Davis, Davis, CA 95616, USA
Abhaya M. Dandekar
Plant Sciences, UC Davis, Davis, CA 95616, USA
Edwin Civerolo
San Joaquin Valley Agricultural Sciences Center, USDA-ARS, Parlier, Parlier, CA 93648, USA
John J. Marchalonis
Department of Immunobiology, University of Arizona College of Medicine P.O. Box 24-5049 Tucson, AZ 85724
Goutam Gupta
Biosciences Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA

ABSTRACT

The emergence of pathogens and toxins with resistance against conventional drugs, vaccines, and host defense peptides and proteins warrants novel countermeasures that can efficiently capture and rapidly clear them. This article examines the utility of chimeric proteins with capture and clearance domains as a novel countermeasure against pathogens and their toxins. The capture and clearance domains are chosen from the large repertoire of host defense peptides and proteins. Although individual capture and clearance domains are rendered ineffective by pathogenic resistance mechanisms, chimeric scaffolds can be designed to retain their antimicrobial activity, even in the face of pathogenic resistance. Here, initial studies on the design of chimeric proteins targeted against (1) intact bacteria such as Xylella fastidiosa (plant pathogens), Salmonella spp. (food-borne pathogens), and Staphylococcus aureus (blood-borne pathogens); and (2) lethal toxins from Bacillus anthracis are described.


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