Work

Lysocin E Targeting Menaquinone in the Membrane of Mycobacterium tuberculosis Is a Promising Lead Compound for Antituberculosis Drugs

Year: 2022

Type: article

Abstract: activity against both drug-susceptible and drug-resistant Mycobacterium tuberculosis var. tuberculosis and dormant mycobacteria. Lysocin E is likely bound to menaquinone, causing M. tuberculosis membrane disruption, inhibition of oxygen consumption, and ATP synthesis. Thus, we have concluded that the high antituberculosis activity of lysocin E is attributable to its synergistic effects of membrane disruption and respiratory inhibition. The efficacy of lysocin E against intracellular M. tuberculosis in macrophages was lower than its potent activity against M. tuberculosis 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.

Source: Antimicrobial Agents and Chemotherapy

DOI: 10.1128/aac.00171-22

Authors: Geberemichal Geberetsadik, Akane Inaizumi, Akihito Nishiyama, Takehiro Yamaguchi, Hiroshi Hamamoto, Suresh Panthee, Aki Tamaru, Manabu Hayatsu, Yusuke Mizutani, Shaban Amina Kaboso, Mariko Hakamata, Aleksandr Ilinov, Yuriko Ozeki, Yoshitaka Tateishi, Kazuhisa Sekimizu, Sohkichi Matsumoto

Institutions: Asossa University, Niigata University, National Institute of Infectious Diseases, Teikyo University, Texas A&M University, Osaka Prefectural Institute of Public Health, Osaka Institute of Public Health, Hokkaido University, Krasnoyarsk State Medical University, Universitas Airlangga

Language: English

Topic: Tuberculosis Research and Epidemiology

Subfield: Infectious Diseases

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: Japan Agency for Medical Research and Development, Ministry of Education, Culture, Sports, Science and Technology, Japan Society for the Promotion of Science

Awards: G1326020628, Functional analysis of novel substances from food materials showing strong abilities of innate immunity stimulation, Elucidation of Molecular Mechanism of Mycobacterial Latency via Mycobacterial Membrane Vesicles, G3806304657, G4191322110, G4267848195, Expanding functional genomics of nontuberculous mycobacteria for establishing strategies for prevention, predictive diagnosis and drug development, Development of rapid diagnosis of drug sensitivity and optimal choice of chemotherapeutic regimen in MAC pulmonary disease by making use of TnSeq, Establishment of the therapeutic platform of MAC pulmonary disease by identifying essential genes covering the genetic diversity of clinical strains, 結核の発病予測向上と治療期間短縮を目指した生物学的要因の探索

OpenAlex ID: W4291786491

FWCI: 1.514

Cites: 23

Cited by: 18

Related to: 10