Small molecule inhibitors of the fosfomycin resistance enzyme FosM from Mycobacterium abscessus

Skye Chiasson; Tatum Smith; Landon Bello; Nishad Thamban Chandrika; Keith D. Green; Sylvie Garneau-Tsodikova; Matthew K. Thompson

doi:10.1016/j.bbagen.2023.130444

Small molecule inhibitors of the fosfomycin resistance enzyme FosM from Mycobacterium abscessus

Skye Chiasson, Tatum Smith, Landon Bello, Nishad Thamban Chandrika, Keith D. Green, Sylvie Garneau-Tsodikova, Matthew K. Thompson

Research output: Contribution to journal › Article › peer-review

Abstract

Fosfomycin is a safe broad-spectrum antibiotic that has not achieved widespread use because of the emergence of fosfomycin-modifying enzymes. Inhibition of fosfomycin-modifying enzymes could be used to help combat pathogens like Mycobacterium abscessus. Our previous work identified several inhibitors for the enzyme FosB from Staphylococcus aureus. We have tested those same compounds for inhibition of FosM, the fosfomycin-modifying enzyme from M. abscessus. The work described here will be used as the basis for more detailed studies into the inhibition of FosM.

Original language	English
Article number	130444
Journal	Biochimica et Biophysica Acta - General Subjects
Volume	1867
Issue number	10
DOIs	https://doi.org/10.1016/j.bbagen.2023.130444
State	Published - Oct 2023

Bibliographical note

Publisher Copyright:
© 2023 Elsevier B.V.

Funding

This work was supported by The University of Alabama startup funds, the Cystic Fibrosis Foundation Grant # THOMPS2010 , and National Institutes of Health grant # 1R15GM148956 . This work was supported by The University of Alabama startup funds, the Cystic Fibrosis Foundation Grant #THOMPS2010, and National Institutes of Health grant #1R15GM148956.M. K. T. would like to acknowledge the generosity of the Richard N. Armstrong family and Vanderbilt University Department of Biochemistry for initial laboratory equipment along with plasmids and reagents specific to this project. S. C. would like to acknowledge the Department of Education GAANN Grant #P200A150329. M. K. T. would like to acknowledge the generosity of the Richard N. Armstrong family and Vanderbilt University Department of Biochemistry for initial laboratory equipment along with plasmids and reagents specific to this project. S. C. would like to acknowledge the Department of Education GAANN Grant # P200A150329 .

Funders	Funder number
National Institutes of Health (NIH)	1R15GM148956
U.S. Department of Education, OSERS	P200A150329
Cystic Fibrosis Foundation Headquarters	THOMPS2010
Department of Chemistry, Vanderbilt University
University of Alabama

Keywords

Antimicrobial resistance
ForM
Fosfomycin
Mycobacterium abscessus

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology

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10.1016/j.bbagen.2023.130444

Cite this

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title = "Small molecule inhibitors of the fosfomycin resistance enzyme FosM from Mycobacterium abscessus",

abstract = "Fosfomycin is a safe broad-spectrum antibiotic that has not achieved widespread use because of the emergence of fosfomycin-modifying enzymes. Inhibition of fosfomycin-modifying enzymes could be used to help combat pathogens like Mycobacterium abscessus. Our previous work identified several inhibitors for the enzyme FosB from Staphylococcus aureus. We have tested those same compounds for inhibition of FosM, the fosfomycin-modifying enzyme from M. abscessus. The work described here will be used as the basis for more detailed studies into the inhibition of FosM.",

keywords = "Antimicrobial resistance, ForM, Fosfomycin, Mycobacterium abscessus",

author = "Skye Chiasson and Tatum Smith and Landon Bello and Chandrika, \{Nishad Thamban\} and Green, \{Keith D.\} and Sylvie Garneau-Tsodikova and Thompson, \{Matthew K.\}",

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doi = "10.1016/j.bbagen.2023.130444",

language = "English",

volume = "1867",

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AU - Chiasson, Skye

AU - Smith, Tatum

AU - Bello, Landon

AU - Chandrika, Nishad Thamban

AU - Green, Keith D.

AU - Garneau-Tsodikova, Sylvie

AU - Thompson, Matthew K.

PY - 2023/10

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AB - Fosfomycin is a safe broad-spectrum antibiotic that has not achieved widespread use because of the emergence of fosfomycin-modifying enzymes. Inhibition of fosfomycin-modifying enzymes could be used to help combat pathogens like Mycobacterium abscessus. Our previous work identified several inhibitors for the enzyme FosB from Staphylococcus aureus. We have tested those same compounds for inhibition of FosM, the fosfomycin-modifying enzyme from M. abscessus. The work described here will be used as the basis for more detailed studies into the inhibition of FosM.

KW - Antimicrobial resistance

KW - ForM

KW - Fosfomycin

KW - Mycobacterium abscessus

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Small molecule inhibitors of the fosfomycin resistance enzyme FosM from Mycobacterium abscessus

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

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