DNA gyrase gyrA mutations in ciprofloxacin-resistant strains of Staphylococcus aureus: close similarity with quinolone resistance mutations in Escherichia coli

Sreedharan, S; Oram, Mark; Jensen, Barbara; Peterson, Lance R.; Fisher, L. Mark

doi:10.1128/jb.172.12.7260-7262.1990

Cited by 165 publications

(144 citation statements)

References 22 publications

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“…On the basis of fluoroquinolone resistance mechanisms in E. coli, other workers have cloned and partially sequenced the gyr genes of S. aureus (31) Using genetic analysis and physical mapping techniques, we identified a novel gene that confers fluoroquinolone resistance in S. aureus. The linkage of these loci to thrB and trp suggests that ofxC is a genetically distinct gene from cfxB, but this hypothesis could not be confirmed by a direct cross between ofxC and cfxB.…”

Section: Discussionmentioning

confidence: 99%

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A novel locus conferring fluoroquinolone resistance in Staphylococcus aureus

1991

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Staphylococci have long been recognized as important agents of community-and hospital-acquired infections. When ciprofloxacin was released in the United States in 1987, it was hoped that it would be useful for the treatment of infections caused by multidrug-resistant strains of Staphylococcus aureus. The isolation of fluoroquinolone-resistant S. aureus (37), however, soon followed the introduction of these agents.Little is known about resistance mechanisms in S. aureus, but the mechanisms of fluoroquinolone resistance in Escherichia coli have been well described. In E. coli, the enzyme DNA gyrase is the target of fluoroquinolone action (5,9,11,34). DNA gyrase catalyzes the ATP-dependent supercoiling of DNA and the catenation and decatenation of DNA circles (4, 6). The enzyme is a tetramer of two A and two B subunits, encoded by the gyrA and gyrB genes, respectively. Mutations in either gene may confer quinolone resistance in E. coli. Distinct DNA gyrases have been isolated from the gram-positive species Bacillus subtilis (33) and Micrococcus luteus (18). DNA supercoiling activity has been identified in a cell lysate from one strain of S. aureus (35). A second mechanism of resistance to fluoroquinolones in E. coli is reduced drug accumulation associated with decreased expression of outer membrane porin protein OmpF (9, 10). S. aureus lacks an outer membrane; thus, drug resistance mechanisms must differ between these two species.Two mechanisms of quinolone resistance have been proposed in S. aureus. In one study, a DNA fragment that confers quinolone resistance was cloned from S. aureus in E. coli. This fragment appears to encode a hydrophobic protein that may be membrane associated. Introduction of this locus (norA) on a plasmid into E. coli and S. aureus resulted in resistance and reduced accumulation of some quinolones (39). In a second study, point mutations in the gyrA gene of

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Section: Discussionmentioning

confidence: 99%

“…Introduction of this locus (norA) on a plasmid into E. coli and S. aureus resulted in resistance and reduced accumulation of some quinolones (39). In a second study, point mutations in the gyrA gene of S. aureus were identified in quinolone-resistant members of susceptible and resistant pairs of clinical isolates (31).…”

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A novel locus conferring fluoroquinolone resistance in Staphylococcus aureus

1991

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“…For example, two adjacent nucleotide changes can result in markedly increased antibiotic drug resistance in bacterial pathogens (40,41). Biological waste disposal and decontamination practices, e.g., in hospitals where antibiotic-resistant infections are common, are focused on controlling organisms rather than free DNA molecules, and usually result in only partial DNA fragmentation (42).…”

Section: Possible Implications and Perspectivesmentioning

confidence: 99%

Bacterial natural transformation by highly fragmented and damaged DNA

Overballe‐Petersen¹,

Harms

Orlando³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

177

142

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DNA molecules are continuously released through decomposition of organic matter and are ubiquitous in most environments. Such DNA becomes fragmented and damaged (often <100 bp) and may persist in the environment for more than half a million years. Fragmented DNA is recognized as nutrient source for microbes, but not as potential substrate for bacterial evolution. Here, we show that fragmented DNA molecules (≥20 bp) that additionally may contain abasic sites, cross-links, or miscoding lesions are acquired by the environmental bacterium Acinetobacter baylyi through natural transformation. With uptake of DNA from a 43,000-y-old woolly mammoth bone, we further demonstrate that such natural transformation events include ancient DNA molecules. We find that the DNA recombination is RecA recombinase independent and is directly linked to DNA replication. We show that the adjacent nucleotide variations generated by uptake of short DNA fragments escape mismatch repair. Moreover, doublenucleotide polymorphisms appear more common among genomes of transformable than nontransformable bacteria. Our findings reveal that short and damaged, including truly ancient, DNA molecules, which are present in large quantities in the environment, can be acquired by bacteria through natural transformation. Our findings open for the possibility that natural genetic exchange can occur with DNA up to several hundreds of thousands years old. microbial evolution | horizontal gene transfer | DNA degradation | early life | anachronistic evolution

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“…There is always cross resistance between different quinolones which is mainly due to mutations affecting the gyr A-gene. The corresponding amino acid substitutions occurring in a definite region of the gyrase A protein of ciprofloxacin-resistant clinical isolates of S. aureus are analogous to those in quinolone-resistant Escherichia coli [4]. Also an efflux mechanism has been 414 W. WITTE AND H. GRIMM described for norfloxacin-resistant S. aureus [5].…”

Section: Introductionmentioning

confidence: 99%

Occurrence of quinolone resistance inStaphylococcus aureusfrom nosocomial infection

Witte

Grimm²

1992

Epidemiol. Infect.

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SUMMARYAmong 63 Staphylococcus aureus isolates (one isolate per one patient) counted from infections (from August to November 1991) in hospital T., eight exhibited resistance to fluoroquinolones. Seven of these quinolone-resistant isolates were multiply-and methicillin-resistant S. aureus (QR-MRSA). The results of phage-, plasmid-and genotyping (pulsed field electrophoresis) revealed that six different strain-clones of these MRSA were spread in the hospital. In vitro spontaneous mutants resistant to fluoroquinolones are 10-100-fold more frequent in MRSA than in other S. aureus when selected on isosensitest-agar containing 1 #g/ml of ciprofloxacin. However, the same mutant frequencies were found in strain 8325-4 with and without the mecA-determinant. The resistance phenotype was stable over 30 generations of subculture in nutrient broth as well in natural quinolone resistant MRSA as in mutants of other types of S. aureus selected in vitro. The phenotypic association of quinolone resistance and MRSA is rather likely due to a higher frequency of spontaneous resistant mutants which are present in natural populations of MRSA. Data of chemotherapy prior to the isolation of S. aureus show that three of seven patients from whom QR-MRSA were isolated were treated with a quinolone. In eight cases of infections with non-MRSA and quinolone treatment the isolated S. aureus strains were in vitro sensitive to quinolones.

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DNA gyrase gyrA mutations in ciprofloxacin-resistant strains of Staphylococcus aureus: close similarity with quinolone resistance mutations in Escherichia coli

Cited by 165 publications

References 22 publications

A novel locus conferring fluoroquinolone resistance in Staphylococcus aureus

A novel locus conferring fluoroquinolone resistance in Staphylococcus aureus

Bacterial natural transformation by highly fragmented and damaged DNA

Occurrence of quinolone resistance inStaphylococcus aureusfrom nosocomial infection

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