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15.6 Recent Major Developments
15.6.1 PK34
PK34 is derived from Mycobacterium phage D29. The precursor of PK34 is a hypothetical protein D29p63. D29p63 is a highly conserved small protein family, found
in several mycobacteriophages. PK34 is a peptide composed of 34 amino acids that
include eight basic and five acidic amino acids with a predicted isoelectric point (pI)
of 10.25 (Wei et al. 2013). PK34 inhibits the growth of M. tuberculosis H37Rv with
an MIC of 50 μg/mL. In addition to antimycobacterial activity, PK34 inhibits various proinflammatory cytokines, leading to reduced inflammation and granuloma
formation in a mouse model of infection.
15.6.2 HCL2
HCL2 peptide derived from human mitochondrial protein COX3 was isolated by
Samuchiwal et al. (2014). The targets for HCL2 are ESAT-6 and CFP10. Secreted
antigenic ESAT-6 and CFP10 are virulence factors that play an important role in the
pathogenesis of M. tuberculosis and are secreted into the extracellular matrix during
broth culture of M. tuberculosis. Coexpression of HCL2 along with ESAT6 and
CFP10 in a bacterial three-hybrid system leads to disruption of binding association
of ESAT6 and CFP10. HCL2 could disrupt the heterodimeric interaction between
ESAT-6 and CFP10 in vivo. A constitutive expression of HCL2 in M. tuberculosis
H37Rv significantly inhibits the growth of the bacterium. Electron microscopic
studies of these cells revealed feeble cells with porous membranes. In vivo studies
with THP1 cells showed that HCL2-expressing M. tuberculosis showed reduced
survival compared to the wild type. An antigen-specific hyperproliferative response
was observed in mice infected with H37Rv expressing HCL2. The potential for use
of HCL2 also lies in its target specificity, as it was found to be nontoxic to other
bacteria as well as mice.
15.6.3 Temporins
Mohanram and Bhattacharjya (2016) have demonstrated the nonhemolytic and
broad-spectrum antibacterial properties of LG21, an LPS–temporin B hybrid. The
LG21 hybrid has a helical conformation forming a lollipop-like shape. The hydrophilic “head” consists of compacted bulky aromatic/cationic side chain/side chain
packing and the N-terminal end constitutes the thinner “stick” which is hydrophobic
in nature.
15 Antimycobacterial Peptides
15.6 Recent Major Developments
15.6.1 PK34
PK34 is derived from Mycobacterium phage D29. The precursor of PK34 is a hypothetical protein D29p63. D29p63 is a highly conserved small protein family, found
in several mycobacteriophages. PK34 is a peptide composed of 34 amino acids that
include eight basic and five acidic amino acids with a predicted isoelectric point (pI)
of 10.25 (Wei et al. 2013). PK34 inhibits the growth of M. tuberculosis H37Rv with
an MIC of 50 μg/mL. In addition to antimycobacterial activity, PK34 inhibits various proinflammatory cytokines, leading to reduced inflammation and granuloma
formation in a mouse model of infection.
15.6.2 HCL2
HCL2 peptide derived from human mitochondrial protein COX3 was isolated by
Samuchiwal et al. (2014). The targets for HCL2 are ESAT-6 and CFP10. Secreted
antigenic ESAT-6 and CFP10 are virulence factors that play an important role in the
pathogenesis of M. tuberculosis and are secreted into the extracellular matrix during
broth culture of M. tuberculosis. Coexpression of HCL2 along with ESAT6 and
CFP10 in a bacterial three-hybrid system leads to disruption of binding association
of ESAT6 and CFP10. HCL2 could disrupt the heterodimeric interaction between
ESAT-6 and CFP10 in vivo. A constitutive expression of HCL2 in M. tuberculosis
H37Rv significantly inhibits the growth of the bacterium. Electron microscopic
studies of these cells revealed feeble cells with porous membranes. In vivo studies
with THP1 cells showed that HCL2-expressing M. tuberculosis showed reduced
survival compared to the wild type. An antigen-specific hyperproliferative response
was observed in mice infected with H37Rv expressing HCL2. The potential for use
of HCL2 also lies in its target specificity, as it was found to be nontoxic to other
bacteria as well as mice.
15.6.3 Temporins
Mohanram and Bhattacharjya (2016) have demonstrated the nonhemolytic and
broad-spectrum antibacterial properties of LG21, an LPS–temporin B hybrid. The
LG21 hybrid has a helical conformation forming a lollipop-like shape. The hydrophilic “head” consists of compacted bulky aromatic/cationic side chain/side chain
packing and the N-terminal end constitutes the thinner “stick” which is hydrophobic
in nature.
15 Antimycobacterial Peptides