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

Producción científica: Article › revisión exhaustiva

Resumen

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.

Idioma original	English
Número de artículo	130444
Publicación	Biochimica et Biophysica Acta - General Subjects
Volumen	1867
N.º	10
DOI	https://doi.org/10.1016/j.bbagen.2023.130444
Estado	Published - oct 2023

Nota bibliográfica

Publisher Copyright:
© 2023 Elsevier B.V.

Financiación

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 .

Financiadores	Número del financiador
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

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology

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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",

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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

Y1 - 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

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