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Study of Mutations in the DNA gyrase gyrA Gene of Escherichia coli.

Pourahmad Jaktaji R, Mohiti E - Iran J Pharm Res (2010)

Bottom Line: Most of ciprofloxacin-resistant mutants possess mutations in QRDR region and precisely at Ser-83.However, mutations outside of this region were also found at Tyr-50 and Ala-119.In conclusion, the presence of mutations at amino acids 50 and 119 suggests that in addition to QRDR section and Tyr-122, these sites are also essential for DNA gyrase activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Faculty of Science, University of Shahrekord, Shahrekord, Iran.

ABSTRACT
Quinolones are a large and widely consumed class of synthetic drugs. Expanded-spectrum quinolones, like ciprofloxacin are highly effective against Gram-negative bacteria, especially Escherichia coli. In E. coli the major target for quinolones is DNA gyrase. This enzyme is composed of two subunits, GyrA and GyrB encoding by gyrA and gyrB, respectively. Mutations in either of these genes cause quinolone resistance. Mutations in QRDR section of gyrA are more common in quinolone resistant clinical isolates. However, a mutation outside of this region was also reported. Thus, this study was aimed to provide more information on mutations sites in gyrA. For this purpose, spontaneous ciprofloxacin resistant mutants arisen in cultures of E. coli ATCC 25922 and MG1655 were isolated on LB agar containing ciprofloxacin. Next, the MICs of these clones were measured and the presence of mutation in gyrA was investigated. Results showed that the frequency of ciprofloxacin resistant mutants in cultures of E. coli strains was low. However, these mutants had different MICs, depending on the day of isolation. Most of ciprofloxacin-resistant mutants possess mutations in QRDR region and precisely at Ser-83. However, mutations outside of this region were also found at Tyr-50 and Ala-119. In conclusion, the presence of mutations at amino acids 50 and 119 suggests that in addition to QRDR section and Tyr-122, these sites are also essential for DNA gyrase activity.

No MeSH data available.


Related in: MedlinePlus

Structure of ciprofloxacin
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Figure 1: Structure of ciprofloxacin

Mentions: Quinolones are a large and widely consumed class of synthetic drugs (1). First-generation (acidic) quinolones, including nalidixic acid and oxolinic acid, have been only used for treatment of urinary tract infections (2). However, modification of subsequent generations has increased their spectrum and potency. One of these modifications has been the addition of a fluorine atom at position C-6 of drug molecules, for instance in ciprofloxacin (CFX), which leads to wide potent activity against different Gram-negative bacteria (1). Moreover, due to the presence of a secondary amine in addition to carboxylic acid found in all members of family, CFX is a amphoteric quinolone rather than acidic one (Figure 1).


Study of Mutations in the DNA gyrase gyrA Gene of Escherichia coli.

Pourahmad Jaktaji R, Mohiti E - Iran J Pharm Res (2010)

Structure of ciprofloxacin
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3869551&req=5

Figure 1: Structure of ciprofloxacin
Mentions: Quinolones are a large and widely consumed class of synthetic drugs (1). First-generation (acidic) quinolones, including nalidixic acid and oxolinic acid, have been only used for treatment of urinary tract infections (2). However, modification of subsequent generations has increased their spectrum and potency. One of these modifications has been the addition of a fluorine atom at position C-6 of drug molecules, for instance in ciprofloxacin (CFX), which leads to wide potent activity against different Gram-negative bacteria (1). Moreover, due to the presence of a secondary amine in addition to carboxylic acid found in all members of family, CFX is a amphoteric quinolone rather than acidic one (Figure 1).

Bottom Line: Most of ciprofloxacin-resistant mutants possess mutations in QRDR region and precisely at Ser-83.However, mutations outside of this region were also found at Tyr-50 and Ala-119.In conclusion, the presence of mutations at amino acids 50 and 119 suggests that in addition to QRDR section and Tyr-122, these sites are also essential for DNA gyrase activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Faculty of Science, University of Shahrekord, Shahrekord, Iran.

ABSTRACT
Quinolones are a large and widely consumed class of synthetic drugs. Expanded-spectrum quinolones, like ciprofloxacin are highly effective against Gram-negative bacteria, especially Escherichia coli. In E. coli the major target for quinolones is DNA gyrase. This enzyme is composed of two subunits, GyrA and GyrB encoding by gyrA and gyrB, respectively. Mutations in either of these genes cause quinolone resistance. Mutations in QRDR section of gyrA are more common in quinolone resistant clinical isolates. However, a mutation outside of this region was also reported. Thus, this study was aimed to provide more information on mutations sites in gyrA. For this purpose, spontaneous ciprofloxacin resistant mutants arisen in cultures of E. coli ATCC 25922 and MG1655 were isolated on LB agar containing ciprofloxacin. Next, the MICs of these clones were measured and the presence of mutation in gyrA was investigated. Results showed that the frequency of ciprofloxacin resistant mutants in cultures of E. coli strains was low. However, these mutants had different MICs, depending on the day of isolation. Most of ciprofloxacin-resistant mutants possess mutations in QRDR region and precisely at Ser-83. However, mutations outside of this region were also found at Tyr-50 and Ala-119. In conclusion, the presence of mutations at amino acids 50 and 119 suggests that in addition to QRDR section and Tyr-122, these sites are also essential for DNA gyrase activity.

No MeSH data available.


Related in: MedlinePlus