PMID:2285321
| Citation |
Juhl, MJ and Clark, DP (1990) Thiophene-degrading Escherichia coli mutants possess sulfone oxidase activity and show altered resistance to sulfur-containing antibiotics. Appl. Environ. Microbiol. 56:3179-85 |
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| Abstract |
We have previously isolated mutants of Escherichia coli which show increased oxidation of heterocyclic furan and thiophene substrates. We have now found that strains carrying the thdA mutation express a novel enzyme activity which oxidizes a variety of substrates containing a sulfone (SO2) moiety. Both heterocyclic sulfones (e.g., tetramethylene sulfone) and simple aliphatic sulfones (e.g., ethyl sulfone) were oxidized. The thdA mutants were more resistant than wild-type strains to aromatic sulfone antibiotics such as dapsone. In contrast they showed increased susceptibility to thiolutin, a cyclic antibiotic containing sulfur at the sulfide level of oxidation. Several new thdA mutant alleles were isolated by selecting for increased oxidation of various aliphatic sulfur compounds. These new thdA mutants showed similar sulfone oxidase activity and the same map location (at 10.7 min) as the original thdA1 mutation. The constitutive fadR mutation was required for the phenotypic expression of thdA-mediated oxidation of sulfur compounds. However, the thdA-directed expression of sulfone oxidase activity was not fadR dependent. The thdC and thdD mutations probably protect against the toxicity of thiophene derivatives rather than conferring improved metabolic capability. |
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| Keywords |
Anti-Bacterial Agents/pharmacology; Bacterial Proteins/genetics; Bacterial Proteins/metabolism; Dapsone/metabolism; Dapsone/pharmacology; Drug Resistance, Microbial; Escherichia coli/drug effects; Escherichia coli/genetics; Escherichia coli/metabolism; Furans/metabolism; Genes, Bacterial; Oxidation-Reduction; Oxidoreductases/genetics; Oxidoreductases/metabolism; Oxidoreductases Acting on Sulfur Group Donors; Pyrrolidinones/pharmacology; Substrate Specificity; Sulfones/metabolism; Sulfoxides/metabolism; Thiazoles/metabolism; Thiazoles/pharmacology; Thiophenes/metabolism |
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Alleles and Phenotypes
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| Allele | Nt change(s) | AA change(s) | Phenotype: Type | Phenotype: Description | Reference | Availability | Comments |
|---|---|---|---|---|---|---|---|
|
thdA2 |
Mutation to the thdA gene |
Sensitivity to |
In minimum medium there is hypersensitivity toward thiolutin. |
These results were seen in mutant thdA3 as well as strains NAR11 and NAR41. | |||
|
thdA1 in NAR11 |
Mutation to the thdA gene |
Resistant to |
Dapsone resistance developed. |
This was also seen in strain NAR20. | |||
|
thdA1 in NAR11 |
Mutation to the thdA gene |
Resistant to |
Thiazolsulfone resistance developed. |
This was also seen in strain NAR20 and NAR30. See page 3181 for full details. | |||
|
thdA1 & fadR in MW5 |
Mutation to the thdA and fadR mutation. |
Resistant to |
Thiophene and Furan derivatives. |
It was found that the fadR was needed in conjunction to the thdA mutation in order for resistance to develop. See table 3 for full oxidation experiment results. | |||
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