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Gene Review

parC  -  DNA topoisomerase IV, subunit A

Escherichia coli str. K-12 substr. MG1655

 
 
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Disease relevance of parC

 

High impact information on parC

  • It is suggested that the parC and parE genes code for the subunits of a new topoisomerase, named topo IV [1].
  • Through mutagenesis, parA and parB were found to be essential for partitioning function, whereas parC did not appear to be required [6].
  • This lethal effect of ciprofloxacin was eliminated by additional mutations mapping in parC, one of the two genes encoding topoisomerase IV [7].
  • The -10 and -35 core promoter sequences are flanked by the two sets of five direct repeats in parC (the ParR boxes) [8].
  • Based on the Escherichia coli co-ordinates, the hotspots most favoured for giving rise to decreased susceptibility and/or full resistance to quinolones are at serine 83 and aspartate 87 of gyrA, and at serine 79 and aspartate 83 for parC [9].
 

Chemical compound and disease context of parC

 

Biological context of parC

  • DNA sequencing revealed point mutations in gyrA (Ser83-Leu, Asp87-Tyr, Asp87-Gly, Asp87-Ala), gyrB (Glu466-Asp, Asp426-Thr), and parC (Ser80-Ile, Ser80-Arg) [11].
  • Blocking protein secretion by thermoinduction of a secA(Ts) strain caused a chromosome segregation defect similar to that in parC mutants, and NO was active [12].
  • In addition, the parC and gyrA genes provide an example of the evolution of essential functions by gene duplication [13].
  • The DNA sequence of the S. typhimurium parC gene was determined and has 56% homology with the first 1400 base pairs of the Escherichia coli gryA gene, which encodes the A subunit of DNA gyrase, and 85% homology with the E. coli parC gene [13].
  • The analysis of the T. whipplei genome database allowed the identification not only of the gyrA gene but also the parC gene encoding the alpha subunit of the natural fluoroquinolone targets DNA gyrase (GyrA) and topoisomerase IV (ParC), respectively [4].
 

Associations of parC with chemical compounds

  • Clinafloxacin was highly active against S. pneumoniae 7785 (MIC, 0.125 microg/ml), and neither gyrA nor parC quinolone resistance mutations alone had much effect on this activity [14].
  • The objective of this study was to analyse an array of ciprofloxacin and norfloxacin derivatives in order to determine those with good activity against bacteria that already present fluoroquinolone resistance associated with mutations in the gyrA and/or parC genes [15].
  • Resistance to nalidixic acid was demonstrated in three isolates, two from patients who had travelled to India. In all three strains the resistance was linked to mutations in the gyrA gene alone or in both gyrA and parC genes [16].
  • However, the isolates with two mutation in gyrA regardless of whether there was a mutation in parC showed high MIC for the three fluoroquinolones (CIP, 0.75 to 32 <or=microg/ml; ENO, 3 to 32 <or=microg/ml; NOR, 3 to 32 <or=microg/ml ) [17].
 

Analytical, diagnostic and therapeutic context of parC

References

  1. New topoisomerase essential for chromosome segregation in E. coli. Kato, J., Nishimura, Y., Imamura, R., Niki, H., Hiraga, S., Suzuki, H. Cell (1990) [Pubmed]
  2. Neisseria gonorrhoeae acquires mutations in analogous regions of gyrA and parC in fluoroquinolone-resistant isolates. Belland, R.J., Morrison, S.G., Ison, C., Huang, W.M. Mol. Microbiol. (1994) [Pubmed]
  3. Cloning and characterization of the parC and parE genes of Streptococcus pneumoniae encoding DNA topoisomerase IV: role in fluoroquinolone resistance. Pan, X.S., Fisher, L.M. J. Bacteriol. (1996) [Pubmed]
  4. Molecular evaluation of antibiotic susceptibility: Tropheryma whipplei paradigm. Masselot, F., Boulos, A., Maurin, M., Rolain, J.M., Raoult, D. Antimicrob. Agents Chemother. (2003) [Pubmed]
  5. Sequence analysis of the gyrA and parC homologues of a wild-type strain of Vibrio parahaemolyticus and its fluoroquinolone-resistant mutants. Okuda, J., Hayakawa, E., Nishibuchi, M., Nishino, T. Antimicrob. Agents Chemother. (1999) [Pubmed]
  6. Molecular analysis of the pRA2 partitioning region: ParB autoregulates parAB transcription and forms a nucleoprotein complex with the plasmid partition site, parS. Kwong, S.M., Yeo, C.C., Poh, C.L. Mol. Microbiol. (2001) [Pubmed]
  7. DNA gyrase and topoisomerase IV on the bacterial chromosome: quinolone-induced DNA cleavage. Chen, C.R., Malik, M., Snyder, M., Drlica, K. J. Mol. Biol. (1996) [Pubmed]
  8. Partitioning of plasmid R1. The parA operon is autoregulated by ParR and its transcription is highly stimulated by a downstream activating element. Jensen, R.B., Dam, M., Gerdes, K. J. Mol. Biol. (1994) [Pubmed]
  9. Mechanisms of fluoroquinolone resistance: an update 1994-1998. Piddock, L.J. Drugs (1999) [Pubmed]
  10. Targeting of DNA gyrase in Streptococcus pneumoniae by sparfloxacin: selective targeting of gyrase or topoisomerase IV by quinolones. Pan, X.S., Fisher, L.M. Antimicrob. Agents Chemother. (1997) [Pubmed]
  11. Antimicrobial susceptibility and molecular characterization of avian pathogenic Escherichia coli isolates. Zhao, S., Maurer, J.J., Hubert, S., De Villena, J.F., McDermott, P.F., Meng, J., Ayers, S., English, L., White, D.G. Vet. Microbiol. (2005) [Pubmed]
  12. Effects of perturbing nucleoid structure on nucleoid occlusion-mediated toporegulation of FtsZ ring assembly. Sun, Q., Margolin, W. J. Bacteriol. (2004) [Pubmed]
  13. A cluster of genes that affects nucleoid segregation in Salmonella typhimurium. Luttinger, A.L., Springer, A.L., Schmid, M.B. New Biol. (1991) [Pubmed]
  14. DNA gyrase and topoisomerase IV are dual targets of clinafloxacin action in Streptococcus pneumoniae. Pan, X.S., Fisher, L.M. Antimicrob. Agents Chemother. (1998) [Pubmed]
  15. Antibacterial evaluation of a collection of norfloxacin and ciprofloxacin derivatives against multiresistant bacteria. Vila, J., Sánchez-Céspedes, J., Sierra, J.M., Piqueras, M., Nicolás, E., Freixas, J., Giralt, E. Int. J. Antimicrob. Agents (2006) [Pubmed]
  16. Susceptibility patterns of enteroaggregative Escherichia coli associated with traveller's diarrhoea: emergence of quinolone resistance. Vila, J., Vargas, M., Ruiz, J., Espasa, M., Pujol, M., Corachán, M., Jiménez de Anta, M.T., Gascón, J. J. Med. Microbiol. (2001) [Pubmed]
  17. Fluoroquinolone resistance and gyrA and parC mutations of Escherichia coli isolated from chicken. Lee, Y.J., Cho, J.K., Kim, K.S., Tak, R.B., Kim, A.R., Kim, J.W., Im, S.K., Kim, B.H. J. Microbiol. (2005) [Pubmed]
  18. Contributions of individual mechanisms to fluoroquinolone resistance in 36 Escherichia coli strains isolated from humans and animals. Everett, M.J., Jin, Y.F., Ricci, V., Piddock, L.J. Antimicrob. Agents Chemother. (1996) [Pubmed]
  19. Genetic characterization of highly fluoroquinolone-resistant clinical Escherichia coli strains from China: role of acrR mutations. Wang, H., Dzink-Fox, J.L., Chen, M., Levy, S.B. Antimicrob. Agents Chemother. (2001) [Pubmed]
  20. Molecular epidemiology and mutations at gyrA and parC genes of ciprofloxacin-resistant Escherichia coli isolates from a Taiwan medical center. Chen, J.Y., Siu, L.K., Chen, Y.H., Lu, P.L., Ho, M., Peng, C.F. Microb. Drug Resist. (2001) [Pubmed]
 
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