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].
• TolCs and TolC are functionally similar since tolC can complement the invasion-defective phenotype of a tolCs mutant, and tolCs is required for export of alpha-haemolysin by Salmonella [2].
• Here, we describe a genetic strategy for isolating missense tolC mutations that abolish the bacteriophage receptor activity of the TolC protein without influencing its role in antibiotic efflux [3].
• We have identified and characterized the outer-membrane protein-encoding gene tolC in the bacterial plant pathogen Erwinia chrysanthemi EC16 [4].

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 an attempt to identify a homologue of the Escherichia coli TolC in V. cholerae, we isolated a DNA fragment (pVC) that enabled an E. coli tolC mutant to grow in the presence of 0.05% deoxycholate (DOC) [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].
• When reintroduced into P. aeruginosa on multicopy plasmids, OpmG was able to complement the susceptibility of an opmG::miniTn5 mutant; however, cloned opmH, the proposed ortholog of Escherichia coli tolC according to our phylogenetic analysis, was able to only partially complement the opmH::miniTn5 mutant [7].

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 [8].
• Antibiotic susceptibility assays of the E. coli tolC-deficient mutant BL923 demonstrated a 64-fold increase in resistance to SDS and ethidium bromide upon introduction of the S. marcescens tolC-like hasF gene [9].

Biological context of tolC

• There was little effect on transcription as judged by the use of an ompF-lac operon fusion strain, and the tolC effect was probably due to a post-transcriptional effect [10].
• Here we report the isolation and characterization of tolC missense mutations that direct the synthesis of mutant TolC proteins partially disabled in their efflux role [11].
• The increased drug resistance and decreased drug accumulation caused by the hns deletion were completely suppressed by deletion of the multifunctional outer membrane channel gene tolC [12].
• Sequencing of the S. marcescens tolC-like hasF gene and subsequent amino acid sequence prediction revealed approximately 80% amino acid homology with the Escherichia coli TolC [9].
• The gene order is tolC dnaG uxaC [13].

Associations of tolC with chemical compounds

• Therefore, a tolC knockout mutant (strain ANS1) was constructed to eliminate the contribution of type I secretion systems to TLM resistance [14].
• In contrast, introduction of a mutant tolC gene did not complement the TolC deficiency and the frequency of MNNG-induced mutations remained high [8].

Analytical, diagnostic and therapeutic context of tolC

• Molecular cloning of the tolC locus of Escherichia coli K-12 with the use of transposon Tn10 [15].

References