Fitness Cost and Compensatory Evolution in Levofloxacin-Resistant Mycobacterium aurum

Author:

Pi Rui1,Liu Qingyun1,Takiff Howard E.234,Gao Qian1ORCID

Affiliation:

1. Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, School of Basic Medical Sciences, Shanghai Public Health Clinical Center Fudan University, Shanghai, China

2. Integrated Mycobacterial Pathogenomics Unit, Institut Pasteur, Paris, France

3. Department of Tuberculosis Control and Prevention, Shenzhen Nanshan Centre for Chronic Disease Control, Shenzhen, China

4. Instituto Venezolano de Investigaciones Cientificas, Caracas, Venezuela

Abstract

We isolated spontaneous levofloxacin-resistant strains of Mycobacterium aurum to study the fitness cost and compensatory evolution of fluoroquinolone resistance in mycobacteria. Five of six mutant strains with substantial growth defects showed restored fitness after being serially passaged for 18 growth cycles, along with increased cellular ATP level. Whole-genome sequencing identified putative compensatory mutations in the glgC gene that restored the fitness of the resistant strains, presumably by altering the bacterial energy metabolism.

Funder

MOST | National Science and Technology Program during the Twelfth Five-year Plan Period

National Natural Science Foundation of China

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

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