Azetidines Kill Multidrug-Resistant Mycobacterium tuberculosis without Detectable Resistance by Blocking Mycolate Assembly

Author:

Cui Yixin1,Lanne Alice2,Peng Xudan3,Browne Edward4,Bhatt Apoorva2,Coltman Nicholas J.5ORCID,Craven Philip1ORCID,Cox Liam R.1ORCID,Cundy Nicholas J.1ORCID,Dale Katie2,Feula Antonio1,Frampton Jon6,Fung Martin7,Morton Michael8,Goff Aaron9,Salih Mariwan1,Lang Xingfen3,Li Xingjian13,Moon Chris10,Pascoe Jordan10,Portman Vanessa4,Press Cara2,Schulz-Utermoehl Timothy4,Lee Suki7,Tortorella Micky D.37,Tu Zhengchao3,Underwood Zoe E.10ORCID,Wang Changwei3,Yoshizawa Akina1,Zhang Tianyu3ORCID,Waddell Simon J.9ORCID,Bacon Joanna10,Alderwick Luke211ORCID,Fossey John S.1ORCID,Neagoie Cleopatra3712ORCID

Affiliation:

1. School of Chemistry, University of Birmingham, Edgbaston, Birmingham, West Midlands B15 2TT, U.K.

2. Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Edgbaston, Birmingham, West Midlands B15 2TT, U.K.

3. State Key Laboratory of Respiratory Disease, China-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Science, 190 Kai Yuan Avenue, Science Park, Guangzhou 510530, China

4. Sygnature Discovery, The Discovery Building, BioCity, Pennyfoot Street, Nottingham NG1 1GR, U.K.

5. School of Biosciences, University of Birmingham, Edgbaston, Birmingham, West Midlands B15 2TT, U.K.

6. College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, West Midlands B15 2TT, U.K.

7. Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, 15 Science Park West Avenue NT, Hong Kong SAR

8. ApconiX Ltd, BIOHUB at Alderly Park, Nether Alderly, Cheshire SK10 4TG, U.K.

9. Department of Global Health and Infection, Brighton and Sussex Medical School, University of Sussex, Falmer BN1 9PX, U.K.

10. TB Research Group, National Infection Service, Public Health England (UKHSA), Manor Farm Road, Porton, Salisbury SP4 0JG, U.K.

11. Discovery Sciences, Charles River Laboratories, Chesterford Research Park, Saffron Walden CB10 1XL, U.K.

12. Visiting Scientist, School of Chemistry, University of Birmingham, Edgbaston, Birmingham, West Midlands B15 2TT, U.K.

Funder

National Key Research and Development Program of China

Public Health England

National Centre for the Replacement Refinement and Reduction of Animals in Research

EPSRC Centre for Doctoral Training in Additive Manufacturing

Chinese Academy of Sciences

Publisher

American Chemical Society (ACS)

Reference82 articles.

1. www.who.int/gho/tb/en/. World Health Organisation: Global Health Observatory (GHO) data www.who.int/gho/tb/en/.

2. Global tuberculosis report 2022; World Health Organization: Geneva, 2022, Licence: CC BY-NC-SA 3.0 IGO.

3. USPHS Tuberculosis Short-Course Chemotherapy Trial 21: Effectiveness, Toxicity, and Acceptability

4. Worldwide Emergence of Extensively Drug-resistant Tuberculosis

5. Multidrug-Resistant Tuberculosis

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