Abstract
The genes encoding the ParC and ParE subunits of topoisomerase IV of Streptococcus pneumoniae, together with the region encoding amino acids 46 to 172 (residue numbers are as in Escherichia coli) of the pneumococcal GyrA subunit, were partially characterized. The gyrA gene maps to a physical location distant from the gyrB and parC loci on the chromosome, whereas parC is closely linked to parE. Ciprofloxacin-resistant (Cpr) clinical isolates of S. pneumoniae had mutations affecting amino acid residues of the quinolone resistance-determining region of ParC (low-level Cpr) or in both quinolone resistance-determining regions of ParC and GyrA (high-level Cpr). Mutations were found in residue positions equivalent to the serine at position 83 and the aspartic acid at position 87 of the E. coli GyrA subunit. Transformation experiments suggest that ParC is the primary target of ciprofloxacin. Mutation in parC appears to be a prerequisite before mutations in gyrA can influence resistance levels.
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- Belland R. J., Morrison S. G., Ison C., Huang W. M. Neisseria gonorrhoeae acquires mutations in analogous regions of gyrA and parC in fluoroquinolone-resistant isolates. Mol Microbiol. 1994 Oct;14(2):371–380. doi: 10.1111/j.1365-2958.1994.tb01297.x. [DOI] [PubMed] [Google Scholar]
- Cullen M. E., Wyke A. W., Kuroda R., Fisher L. M. Cloning and characterization of a DNA gyrase A gene from Escherichia coli that confers clinical resistance to 4-quinolones. Antimicrob Agents Chemother. 1989 Jun;33(6):886–894. doi: 10.1128/aac.33.6.886. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fenoll A., Muñoz R., García E., de la Campa A. G. Molecular basis of the optochin-sensitive phenotype of pneumococcus: characterization of the genes encoding the F0 complex of the Streptococcus pneumoniae and Streptococcus oralis H(+)-ATPases. Mol Microbiol. 1994 May;12(4):587–598. doi: 10.1111/j.1365-2958.1994.tb01045.x. [DOI] [PubMed] [Google Scholar]
- Ferrero L., Cameron B., Manse B., Lagneaux D., Crouzet J., Famechon A., Blanche F. Cloning and primary structure of Staphylococcus aureus DNA topoisomerase IV: a primary target of fluoroquinolones. Mol Microbiol. 1994 Aug;13(4):641–653. doi: 10.1111/j.1365-2958.1994.tb00458.x. [DOI] [PubMed] [Google Scholar]
- Gasc A. M., Kauc L., Barraillé P., Sicard M., Goodgal S. Gene localization, size, and physical map of the chromosome of Streptococcus pneumoniae. J Bacteriol. 1991 Nov;173(22):7361–7367. doi: 10.1128/jb.173.22.7361-7367.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hanahan D. Studies on transformation of Escherichia coli with plasmids. J Mol Biol. 1983 Jun 5;166(4):557–580. doi: 10.1016/s0022-2836(83)80284-8. [DOI] [PubMed] [Google Scholar]
- Kato J., Nishimura Y., Imamura R., Niki H., Hiraga S., Suzuki H. New topoisomerase essential for chromosome segregation in E. coli. Cell. 1990 Oct 19;63(2):393–404. doi: 10.1016/0092-8674(90)90172-b. [DOI] [PubMed] [Google Scholar]
- Luttinger A. The twisted 'life' of DNA in the cell: bacterial topoisomerases. Mol Microbiol. 1995 Feb;15(4):601–606. doi: 10.1111/j.1365-2958.1995.tb02369.x. [DOI] [PubMed] [Google Scholar]
- Margerrison E. E., Hopewell R., Fisher L. M. Nucleotide sequence of the Staphylococcus aureus gyrB-gyrA locus encoding the DNA gyrase A and B proteins. J Bacteriol. 1992 Mar;174(5):1596–1603. doi: 10.1128/jb.174.5.1596-1603.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Muñoz R., Bustamante M., de la Campa A. G. Ser-127-to-Leu substitution in the DNA gyrase B subunit of Streptococcus pneumoniae is implicated in novobiocin resistance. J Bacteriol. 1995 Jul;177(14):4166–4170. doi: 10.1128/jb.177.14.4166-4170.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Peng H., Marians K. J. Escherichia coli topoisomerase IV. Purification, characterization, subunit structure, and subunit interactions. J Biol Chem. 1993 Nov 15;268(32):24481–24490. [PubMed] [Google Scholar]
- Reece R. J., Maxwell A. DNA gyrase: structure and function. Crit Rev Biochem Mol Biol. 1991;26(3-4):335–375. doi: 10.3109/10409239109114072. [DOI] [PubMed] [Google Scholar]
- Ronda C., García J. L., López R. Characterization of genetic transformation in Streptococcus oralis NCTC 11427: expression of the pneumococcal amidase in S. oralis using a new shuttle vector. Mol Gen Genet. 1988 Dec;215(1):53–57. doi: 10.1007/BF00331302. [DOI] [PubMed] [Google Scholar]
- Swanberg S. L., Wang J. C. Cloning and sequencing of the Escherichia coli gyrA gene coding for the A subunit of DNA gyrase. J Mol Biol. 1987 Oct 20;197(4):729–736. doi: 10.1016/0022-2836(87)90479-7. [DOI] [PubMed] [Google Scholar]
- Takiff H. E., Salazar L., Guerrero C., Philipp W., Huang W. M., Kreiswirth B., Cole S. T., Jacobs W. R., Jr, Telenti A. Cloning and nucleotide sequence of Mycobacterium tuberculosis gyrA and gyrB genes and detection of quinolone resistance mutations. Antimicrob Agents Chemother. 1994 Apr;38(4):773–780. doi: 10.1128/aac.38.4.773. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tomasz A. Cellular metabolism in genetic transformation of pneumococci: requirement for protein synthesis during induction of competence. J Bacteriol. 1970 Mar;101(3):860–871. doi: 10.1128/jb.101.3.860-871.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tomasz A. Multiple-antibiotic-resistant pathogenic bacteria. A report on the Rockefeller University Workshop. N Engl J Med. 1994 Apr 28;330(17):1247–1251. doi: 10.1056/NEJM199404283301725. [DOI] [PubMed] [Google Scholar]
- Wang J. C. DNA topoisomerases. Annu Rev Biochem. 1985;54:665–697. doi: 10.1146/annurev.bi.54.070185.003313. [DOI] [PubMed] [Google Scholar]
- Wang Y., Huang W. M., Taylor D. E. Cloning and nucleotide sequence of the Campylobacter jejuni gyrA gene and characterization of quinolone resistance mutations. Antimicrob Agents Chemother. 1993 Mar;37(3):457–463. doi: 10.1128/aac.37.3.457. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wolfson J. S., Hooper D. C. Fluoroquinolone antimicrobial agents. Clin Microbiol Rev. 1989 Oct;2(4):378–424. doi: 10.1128/cmr.2.4.378. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yanisch-Perron C., Vieira J., Messing J. Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors. Gene. 1985;33(1):103–119. doi: 10.1016/0378-1119(85)90120-9. [DOI] [PubMed] [Google Scholar]
- Yoshida H., Bogaki M., Nakamura M., Nakamura S. Quinolone resistance-determining region in the DNA gyrase gyrA gene of Escherichia coli. Antimicrob Agents Chemother. 1990 Jun;34(6):1271–1272. doi: 10.1128/aac.34.6.1271. [DOI] [PMC free article] [PubMed] [Google Scholar]