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About the Authors:
Daniil M. Prigozhin
* E-mail: [email protected]
Affiliation: Department of Molecular and Cell Biology and California Institute for Quantitative Biosciences, University of California, Berkeley, California, 94720, United States of America
Inna V. Krieger
Affiliations Los Alamos National Laboratory, Los Alamos, New Mexico, 87545, United States of America, Department of Biochemistry and Biophysics, Texas A & M University, College Station, Texas, 77843, United States of America
John P. Huizar
Affiliation: Department of Molecular and Cell Biology and California Institute for Quantitative Biosciences, University of California, Berkeley, California, 94720, United States of America
Daniela Mavrici
Affiliation: Department of Molecular and Cell Biology and California Institute for Quantitative Biosciences, University of California, Berkeley, California, 94720, United States of America
Geoffrey S. Waldo
Affiliation: Los Alamos National Laboratory, Los Alamos, New Mexico, 87545, United States of America
Li-Wei Hung
Affiliation: Los Alamos National Laboratory, Los Alamos, New Mexico, 87545, United States of America
James C. Sacchettini
Affiliation: Department of Biochemistry and Biophysics, Texas A & M University, College Station, Texas, 77843, United States of America
Thomas C. Terwilliger
Affiliation: Los Alamos National Laboratory, Los Alamos, New Mexico, 87545, United States of America
Tom Alber
Affiliation: Department of Molecular and Cell Biology and California Institute for Quantitative Biosciences, University of California, Berkeley, California, 94720, United States of America
Introduction
Mycobacterium tuberculosis (Mtb), the etiologic agent of tuberculosis (TB), presents major threats to public health worldwide [1]. Emergence of Mtb strains resistant to the front-line and second-line drugs underscores the necessity of developing new therapeutics [2]. The mycobacterial cell wall, a complex structure responsible for mediating Mtb interactions with the environment, is a validated drug target [3]. The cell wall consists of several layers: peptidoglycan, arabinogalactan, mycolic acids, and the polysaccharide capsule [4]. Key anti-TB drugs target the biosynthesis of arabinogalactan and mycolic acids [3]. Beta-lactams, antibiotics that target peptidoglycan biosynthesis and are effective against diverse bacterial pathogens, have not yet been deployed against Mtb due to the presence of an efficient beta-lactamase. Nonetheless, a combination of meropenem, a beta-lactam, and clavulanate, a beta-lactamase inhibitor, is being tested as a treatment for both active and latent TB [5]. Genetic, biochemical, and structural characterization of enzymes involved in peptidoglycan homeostasis is critical for development of this and other new therapeutics.