Disease relevance of tolC

• In this study, we characterized two genes in the F. tularensis genome, tolC and a gene we term ftlC, whose products have high homology with the Escherichia coli TolC protein [1].
• However, deletion of tolC, but not ftlC, caused a significant attenuation of virulence in a mouse model of tularemia that could be complemented by addition of tolC in trans [1].
• Erwinia chrysanthemi tolC is involved in resistance to antimicrobial plant chemicals and is essential for phytopathogenesis [2].
• A tolC homolog protects the cell from toxicity by mediating the efflux of AQDS [3].

High impact information on tolC

• Thus, tolC is a critical virulence factor of F. tularensis in addition to its role in multidrug resistance, which suggests the presence of a functional type I secretion system [1].
• Neither tolC nor ftlC was required for replication of the live vaccine strain in murine bone marrow-derived macrophages [1].
• In order to create an easily selectable marker in this region, we inserted transposon-10, which carries a gene determining resistance to tetracycline (tet) near 66 min, and the order tolC-dnaG-sigma-tet was determined [4].
• As tolC is a highly pleiotropic locus, affecting the expression of many genes, it is possible that some of the TolC phenotypes are a direct result of this topological change [5].
• BepC fully complemented the resistance to drugs such as chloramphenicol and acriflavine but was incapable of restoring hemolysin secretion in the tolC mutant of E. coli [6].

Chemical compound and disease context of tolC

• When the wild-type E. coli tolC gene was introduced into a strain lacking the gene, TolC function was restored and the frequency of induction by MNNG became similar to that of the wild-type [7].
• A tolC-deficient strain of E. coli (BL923) containing pUCHF/hasF was analyzed for susceptibility to fluoroquinolones (ciprofloxacin, norfloxacin, and ofloxacin), chloramphenicol, sodium dodecyl sulfate (SDS), and ethidium bromide [8].

Biological context of tolC

• We have sequenced about 5 kb of the Escherichia coli chromosome downstream from the tolC gene, looking for a topoisomerase gene [9].

Anatomical context of tolC

• HlyA remained in the periplasm unless the hlyD and tolC gene products were present in addition to the hybrid [10].
• We have investigated the cause of the temporary accumulation of the 46 000-Mr intermediate and we postulate that the presence of a rare codon AGA (Arg) at codon 402 of the tolC mRNA halts translating ribosomes owing to a limiting amount of the tRNAArg (AGA) species in the cell [11].

Associations of tolC with chemical compounds

• Therefore, the avirulent phenotype could be the result of an inability to secrete a necessary virulence factor, or an increased sensitivity to complement and detergents as a result of a subtle alteration in the lipopolysaccharide (LPS) associated with tolC mutations [12].
• No modification of telithromycin accumulation was detected in E. aerogenes acrAB or tolC derivatives compared to that in the parental strain [13].
• The delta tolC mutant was more sensitive to nonane than the delta acrAB mutant [14].
• In contrast, introduction of a mutant tolC gene did not complement the TolC deficiency and the frequency of MNNG-induced mutations remained high [7].

References