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15.1 Introduction
Antimicrobial peptides (AMPs) are cationic, amphipathic short stretches of amino
acid residues that are genetically encoded and have been demonstrated to play an
important role in host innate immunity. These naturally occurring peptides have
been attributed with an array of activities, including broad-spectrum antibacterial,
antiviral, antifungal and antiparasitic activities (Wang et al. 2000). In addition, the
AMPs have properties such as immune modulation, chemotaxis, wound healing and
anticancerous activity. LAMP is a free database (Zhao et al. 2013), available at:
http://biotechlab.fudan.edu.cn/database/lamp, which details over 5000 naturally
occurring as well as synthetic peptides along with the class, structure and major
functions attributed to these peptides. The secondary structures taken up contribute
to the antimicrobial potentials of these peptides.
The AMPs are classified into four classes based on their secondary structures
(Wang 2015):
1. α-Helix
2. β-Hairpin structure
3. Antiparallel β-sheet
4. Linear peptides
Antimicrobial peptides have a unique structure and diverse mechanism of action
(Waghu et al. 2014). Some peptides act on the membrane of the bacteria through
electrostatic interactions, some act on the ion channels thereby changing the internal pH of the organism, other peptides in addition to targeting the membrane can
also act on intracytoplasmic molecules like lipid II, and certain peptides can traverse
the membrane and accumulate inside the cytoplasm, thereby reducing the viability
of the microbe.
The main models explaining membrane disruption include Carpet model, where
peptide aligns parallel to the surface of the membrane, increasing the surface tension of the membrane leading to its disruption. In Barrel-stave model, the hydrophobic end of peptide inserts into the membrane and the hydrophilic ends jutting out,
thus forming pores in the membrane. In “toroidal pore” model, the peptides have
extensive lattice-like conformation with membrane lipids forming pores (Brogden
et al. 2003; Yeaman and Yount 2003; Duplantier and van Hoek 2013). Disruption of
cytochrome C and cell wall synthesis machinery (Wenzel et al. 2014), molecular
electroporation model (Miteva et al. 1999) and sinking raft mechanism (Pokorny
and Almeida 2005) are some of the other models explaining membrane disruption
by AMPs. Mycobacterium tuberculosis complex (MTB complex) consists of M.
tuberculosis, M. africanum and M. bovis and the Bacillus Calmette-Guérin strain,
M. microti, M. canetti, M. caprae, M. pinnipedii, M. suricattae and M. mungi, which
are related species of acid fast bacteria that cause tuberculosis in humans
(Frothingham et al. 1994). Tuberculosis infects one third of the world population,
S.M. Thayil and A.K. Kesavan
15.1 Introduction
Antimicrobial peptides (AMPs) are cationic, amphipathic short stretches of amino
acid residues that are genetically encoded and have been demonstrated to play an
important role in host innate immunity. These naturally occurring peptides have
been attributed with an array of activities, including broad-spectrum antibacterial,
antiviral, antifungal and antiparasitic activities (Wang et al. 2000). In addition, the
AMPs have properties such as immune modulation, chemotaxis, wound healing and
anticancerous activity. LAMP is a free database (Zhao et al. 2013), available at:
http://biotechlab.fudan.edu.cn/database/lamp, which details over 5000 naturally
occurring as well as synthetic peptides along with the class, structure and major
functions attributed to these peptides. The secondary structures taken up contribute
to the antimicrobial potentials of these peptides.
The AMPs are classified into four classes based on their secondary structures
(Wang 2015):
1. α-Helix
2. β-Hairpin structure
3. Antiparallel β-sheet
4. Linear peptides
Antimicrobial peptides have a unique structure and diverse mechanism of action
(Waghu et al. 2014). Some peptides act on the membrane of the bacteria through
electrostatic interactions, some act on the ion channels thereby changing the internal pH of the organism, other peptides in addition to targeting the membrane can
also act on intracytoplasmic molecules like lipid II, and certain peptides can traverse
the membrane and accumulate inside the cytoplasm, thereby reducing the viability
of the microbe.
The main models explaining membrane disruption include Carpet model, where
peptide aligns parallel to the surface of the membrane, increasing the surface tension of the membrane leading to its disruption. In Barrel-stave model, the hydrophobic end of peptide inserts into the membrane and the hydrophilic ends jutting out,
thus forming pores in the membrane. In “toroidal pore” model, the peptides have
extensive lattice-like conformation with membrane lipids forming pores (Brogden
et al. 2003; Yeaman and Yount 2003; Duplantier and van Hoek 2013). Disruption of
cytochrome C and cell wall synthesis machinery (Wenzel et al. 2014), molecular
electroporation model (Miteva et al. 1999) and sinking raft mechanism (Pokorny
and Almeida 2005) are some of the other models explaining membrane disruption
by AMPs. Mycobacterium tuberculosis complex (MTB complex) consists of M.
tuberculosis, M. africanum and M. bovis and the Bacillus Calmette-Guérin strain,
M. microti, M. canetti, M. caprae, M. pinnipedii, M. suricattae and M. mungi, which
are related species of acid fast bacteria that cause tuberculosis in humans
(Frothingham et al. 1994). Tuberculosis infects one third of the world population,
S.M. Thayil and A.K. Kesavan