Escherichia coli genes involved in resistance to pyrazinoic acid, the active component of the tuberculosis drug pyrazinamide.
The natural resistance of Escherichia coli to pyrazinoic acid (POA), the active derivative of pyrazinamide, was investigated. The TolC mutant was found to be more susceptible to POA and other weak acids than the wild-type strain. Mutation in EmrB but not AcrB efflux protein slightly increased POA susceptibility. Two transposon mutants with increased susceptibility to POA were found to harbor mutations in acnA encoding aconitase-1 and ygiY encoding a putative two-component sensor protein. Complementation of the AcnA and YgiY mutants conferred resistance to POA, whereas the complemented TolC mutant became resistant to POA and other weak acids.
Schaller
Alain
A
Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, 615 N. Wolfe Street, Baltimore, MD 21205, USA.
Guo
Ming
M
Gisanrin
Oluwatosin
O
Zhang
Ying
Y
D000581:Amidohydrolases / Q000378:metabolism; D000995:Antitubercular Agents / Q000494:pharmacology*; D003001:Cloning, Molecular; D003470:Culture Media; D004251:DNA Transposable Elements; D004352:Drug Resistance, Microbial; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D005798:Genes, Bacterial; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D009535:Nicotinamidase / Q000378:metabolism; D011718:Pyrazinamide / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D014169:Transformation, Bacterial
D000995:Antitubercular Agents; D003470:Culture Media; D004251:DNA Transposable Elements; D011718:Pyrazinamide; C005296:pyrazinoic acid; D000581:Amidohydrolases; C022490:pyrazinamide deamidase; D009535:Nicotinamidase