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Gene Review

parE  -  DNA topoisomerase IV subunit B

Streptococcus pneumoniae R6

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Disease relevance of parE


High impact information on parE

  • Naturally occurring parC, parE, and gyrA loci containing mutations in the quinolone-resistance-determining regions were introduced by transformation into S. pneumoniae strain R6 individually and in combinations [4].
  • Also evident were examples of interspecific transfer, with two isolates possessing a parE-parC gene region arising from viridans group streptococci [5].
  • An unusual isolate was found that showed only a single parE mutation and for which the ciprofloxacin MIC was lower (2 mg/liter) than that of levofloxacin (8 mg/liter) [6].
  • Eight isolates had amino acid changes at sites other than ParC/S79 and GyrA/S81; several strains contained mutations in gyrB, parE, or both loci [7].
  • The addition of ceftriaxone suppressed mutations in parC but led to a new mutation in parE in both strains [8].

Biological context of parE


Associations of parE with chemical compounds

  • Importantly, when gemifloxacin was examined against strains of S. pneumoniae with well-characterized ciprofloxacin resistance (including mutations in gyrase, parC and parE as well as efflux strains) there was little impact on the in vivo efficacy [11].
  • Eight of the 1037 S. pneumoniae strains were not susceptible to moxifloxacin and had mutations in gyrA (eight strains), parC (four strains) or parE (three strains) [12].
  • Addition of meropenem was able to completely suppress levofloxacin-induced mutations in WB4 and led to only one mutation in parE in KR4 [13].
  • MEASUREMENTS AND MAIN RESULTS: Ciprofloxacin, clinafloxacin, grepafloxacin, levofloxacin, and moxifloxacin were studied at subtherapeutic and therapeutic dosages against three quinolone-susceptible isolates of S. pneumoniae that lacked mutations in parC, parE, and gyrA [14].

Other interactions of parE

  • Non-susceptibility to quinolones was associated with mutations in parC and parE among European isolates [15].

Analytical, diagnostic and therapeutic context of parE

  • Mutations in the quinolone resistance-determining region (QRDR) were characterized by PCR and sequencing of parC, parE, and gyrA [16].


  1. Characterization of a mutation in the parE gene that confers fluoroquinolone resistance in Streptococcus pneumoniae. Perichon, B., Tankovic, J., Courvalin, P. Antimicrob. Agents Chemother. (1997) [Pubmed]
  2. Viridans group streptococci are donors in horizontal transfer of topoisomerase IV genes to Streptococcus pneumoniae. Balsalobre, L., Ferrándiz, M.J., Liñares, J., Tubau, F., de la Campa, A.G. Antimicrob. Agents Chemother. (2003) [Pubmed]
  3. In vitro exchange of fluoroquinolone resistance determinants between Streptococcus pneumoniae and viridans streptococci and genomic organization of the parE-parC region in S. mitis. Janoir, C., Podglajen, I., Kitzis, M.D., Poyart, C., Gutmann, L. J. Infect. Dis. (1999) [Pubmed]
  4. Fitness Costs of Fluoroquinolone Resistance in Streptococcus pneumoniae. Rozen, D.E., McGee, L., Levin, B.R., Klugman, K.P. Antimicrob. Agents Chemother. (2007) [Pubmed]
  5. Molecular evolution perspectives on intraspecific lateral DNA transfer of topoisomerase and gyrase loci in Streptococcus pneumoniae, with implications for fluoroquinolone resistance development and spread. Stanhope, M.J., Walsh, S.L., Becker, J.A., Italia, M.J., Ingraham, K.A., Gwynn, M.N., Mathie, T., Poupard, J.A., Miller, L.A., Brown, J.R., Amrine-Madsen, H. Antimicrob. Agents Chemother. (2005) [Pubmed]
  6. Levofloxacin-resistant invasive Streptococcus pneumoniae in the United States: evidence for clonal spread and the impact of conjugate pneumococcal vaccine. Pletz, M.W., McGee, L., Jorgensen, J., Beall, B., Facklam, R.R., Whitney, C.G., Klugman, K.P. Antimicrob. Agents Chemother. (2004) [Pubmed]
  7. Genetic analyses of mutations contributing to fluoroquinolone resistance in clinical isolates of Streptococcus pneumoniae. Weigel, L.M., Anderson, G.J., Facklam, R.R., Tenover, F.C. Antimicrob. Agents Chemother. (2001) [Pubmed]
  8. Ceftriaxone acts synergistically with levofloxacin in experimental meningitis and reduces levofloxacin-induced resistance in penicillin-resistant pneumococci. Flatz, L., Cottagnoud, M., Kühn, F., Entenza, J., Stucki, A., Cottagnoud, P. J. Antimicrob. Chemother. (2004) [Pubmed]
  9. Fluoroquinolone resistance mutations in the parC, parE, and gyrA genes of clinical isolates of viridans group streptococci. González, I., Georgiou, M., Alcaide, F., Balas, D., Liñares, J., de la Campa, A.G. Antimicrob. Agents Chemother. (1998) [Pubmed]
  10. Failure of levofloxacin treatment in community-acquired pneumococcal pneumonia. Endimiani, A., Brigante, G., Bettaccini, A.A., Luzzaro, F., Grossi, P., Toniolo, A.Q. BMC Infect. Dis. (2005) [Pubmed]
  11. Pharmacodynamics to combat resistance. Woodnutt, G. J. Antimicrob. Chemother. (2000) [Pubmed]
  12. In vitro activity of moxifloxacin against recent community-acquired respiratory tract pathogens isolated in France: a national survey. Decousser, J.W., Allouch, P.Y., Courvalin, P., Leclercq, R. Int. J. Antimicrob. Agents (2002) [Pubmed]
  13. Meropenem prevents levofloxacin-induced resistance in penicillin-resistant pneumococci and acts synergistically with levofloxacin in experimental meningitis. Cottagnoud, P., Cottagnoud, M., Acosta, F., Flatz, L., Kühn, F., Stucki, A., Entenza, J. Eur. J. Clin. Microbiol. Infect. Dis. (2003) [Pubmed]
  14. Evaluation of survival and pharmacodynamic relationships for five fluoroquinolones in a neutropenic murine model of pneumococcal lung infection. Ernst, E.J., Klepser, M.E., Petzold, C.R., Doern, G.V. Pharmacotherapy (2002) [Pubmed]
  15. Antimicrobial resistance of nasopharyngeal pneumococci from children from day-care centres and orphanages in Russia: results of a unique prospective multicentre study. Stratchounski, L.S., Kozlov, R.S., Appelbaum, P.C., Kretchikova, O.I., Kosowska-Shick, K. Clin. Microbiol. Infect. (2006) [Pubmed]
  16. Emergence and epidemiology of fluoroquinolone-resistant Streptococcus pneumoniae strains from Italy: report from the SENTRY Antimicrobial Surveillance Program (2001-2004). Deshpande, L.M., Sader, H.S., Debbia, E., Nicoletti, G., Fadda, G., Jones, R.N. Diagn. Microbiol. Infect. Dis. (2006) [Pubmed]
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