Rapid clearance of bacteria and their toxins: development of therapeutic proteins.
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.
Kunkel
Meghan
M
Biosciences Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
Vuyisich
Momchilo
M
Gnanakaran
Gnana
G
Bruening
George E
GE
Dandekar
Abhaya M
AM
Civerolo
Edwin
E
Marchalonis
John J
JJ
Gupta
Goutam
G
D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001419:Bacteria / Q000187:drug effects*; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015202:Protein Engineering; D054730:Protein Interaction Domains and Motifs; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D001427:Bacterial Toxins; D011993:Recombinant Fusion Proteins