@phdthesis{oai:niigata-u.repo.nii.ac.jp:02000976,
 author = {Weidengus, Gebremichal Gebretsadik},
 month = {2023-04-27, 2023-04-27},
 note = {Tuberculosis remains a public health crisis and a health security threat. There is an urgent need to develop new anti-tuberculosis drugs with novel modes of action to cure drug-resistant tuberculosis and shorten the chemotherapy period by sterilizing tissues infected with dormant bacteria. Lysocin E is an antibiotic that showed antibacterial activity against Staphylococcus aureus by binding to its menaquinone (commonly known as Vitamin K2). Unlike S. aureus, menaquinone is essential in both growing and dormant Mtb. This study aims to evaluate the anti-tuberculosis activities of lysocin E and decipher its mode of action. We show that lysocin E has high in vitro activity against both drug-susceptible and resistant Mycobacterium tuberculosis var. tuberculosis (Mtb), and dormant mycobacteria. Lysocin E is likely bound to menaquinone causing Mtb membrane disruption, inhibition of oxygen consumption and ATP synthesis. Thus, we have concluded that the high anti-tuberculosis activity of lysocin E is attributed to its synergistic effect of membrane disruption and respiratory inhibition. The efficacy of lysocin E against intracellular Mtb in macrophages was lower compared to its potent activity against Mtb in culture medium, probably due to its low ability to penetrate cells, but its efficacy in mice was still superior to that of streptomycin. Our findings indicate that lysocin E is a promising lead compound for the development of a new tuberculosis drug that cures drug-resistant and latent tuberculosis in a shorter period., Antimicrobial Agents and Chemotherapy. 2022, 66(9), e0017122., 新大院博(医)第1097号},
 school = {新潟大学, Niigata University},
 title = {Lysocin E targeting menaquinone in the membrane of Mycobacterium tuberculosis is a promising lead compound for anti-tuberculosis drugs},
 year = {}
}