Biomedical Engineering Reference
In-Depth Information
1.1 New Paradigm for Pathogen Detection
A significant challenge at the forefront of research in the field of biodetection is
multiplex detection of unknown or uncharacterized pathogens or biologically
engineered microbes. Current systems are incapable of identifying these threat
agents because the specific assays have not been developed. In recent years, an
alternative approach to pathogen detection has emerged, in which the presence and
classification of microorganisms are determined by targeting generic factors. This
methodology is part of an emerging direction in the area of differential sensing,
which focuses on pattern-based detection sensors [
4
,
5
]. This trend is underscored
by advances in material science, biotechnology, and engineering that are providing
broader spectrum recognition capabilities (e.g., aptamers, peptides, engineered
proteins, and biomimetic materials) in complement to conventional antibodies
and DNA/RNA oligonucleotide sequences.
Natural and engineered antimicrobial peptides (AMPs) represent an enabling
technology for pattern-based detection systems. AMPs are key players in the innate
immune system that organisms use to kill infectious microorganisms. They recog-
nize molecular patterns on the surface of pathogens, e.g., lipopolysaccharide (LPS),
lipoteichoic acid (LTA), peptidoglycan, and phospholipids, in order to maximize
their antimicrobial efficacy [
6
]. Most AMPs share fundamental structural motifs
that are essential for their broad spectrum activity; however, there are considerable
differences in peptide sequences, lengths, and charges that differentially modulate
lipid membrane association. It has been proposed that cross-reactive AMP arrays,
which interact with overlapping but nonidentical binding specificities to different
microbial targets, can be exploited for broad spectrum discrimination in pathogen
detection assays [
7
,
8
]. Natural and engineered AMPs represent a new genre of
recognition elements that address the critical technology gap comprising the ability
to detect and categorize unknown, emerging, or engineered pathogenic bacteria,
viruses, and other disease-causing agents. Such a capability is central to appropriate
medical countermeasures and decontamination initiatives.
2 AMPs as Recognition Molecules
AMPs are host defense effector molecules found in organisms throughout the
evolutionary spectrum. They are implicated in the killing of microbes by phago-
cytic, epithelial, and other immunologically relevant cells of mammals, while
intricately regulating immune responses [
9
]. These molecules carry out their multi-
tude of functions by utilizing differences that exist between microbial and mamma-
lian cells. Significant distinctions between microbes and mammalian systems
include membrane composition, higher transmembrane potential, and the presence
of capsular polysaccharides, LPS, peptidoglycan, and LTA, some of which can be
stimuli that induce AMP expression [
9
]. The primary determinant of AMPs'
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