AK15 peptide

AK15 is a small mycobacteriophage-derived peptide. AK15 adopted cationic amphiphilic α-helical structure. Both AK15 and AK15–6 directly inhibited M. tb by trehalose 6, 6’-dimycolate (TDM)–binding and membrane–disruption. They both exhibited bactericidal activity, cell selectivity, and synergistic effects with rifampicin, and none induced drug resistance to M. tb. They efficiently attenuated mycobacterial load in the lung of M. tb–infected mice. AK15 and its isomer AK15–6 showed apparent affinity to mycobacterial cord factor. The pre–incubation of AK15 or AK15–6 with TDM blocked the anti–mycobacterial activity of the peptides. AK15 and its isomer AK15–6 impaired the surface morphology of M. tb. AK15 and its isomer AK15–6 increased the passive diffusion of the fluorescent dye into M. tb. AK15 and its isomer AK15–6 induced the leakage of intracellular ATP from M. tb. AK15 and its isomer AK15–6 showed cell selectivity to M. tb. Positively charged residues, aromatic residues and α–helix constitute the key structural requirements of the peptides. AK15 and its isomer AK15–6 showed none induced drug resistance to M. tb. AK15 and its isomer AK15–6 generated synergistic effects with rifampincin against M. tb. AK15 and its isomer AK15–6 exhibited thermal stability and low toxicity to mice. AK15 and its isomer AK15–6 restrained TDM-stimulated inflammatory signaling activation and inflammatory cytokine production in murine macrophages. AK15 and its isomer AK15–6 efficiently protected mice from M. tb infection. AK15 and its isomer AK15–6 enhanced modest basal immune responses in BMDMs and mice.