Mechanisms of Fluoroquinolone Resistance in Staphylococcus aureus

Kaatz, Glenn W.; Seo, Susan M.; Ruble, Cheryl A.

doi:10.1093/infdis/163.5.1080

Cited by 132 publications

(119 citation statements)

References 25 publications

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“…The SA-1199B strain contains a point mutation in grlA (topoisomerase IV A subunit gene) resulting in an amino acid substitution in GrlA (A116E), and it also overexpresses the NorA efflux pump (norA++) by way of a promoter up-mutation. 19,20 Compounds 3, 5, aripiprazole (7), ebastine (8), sertindole (9), and ziprasidone (10) demonstrate an inhibition of EtBr efflux in the SA-1199B strain of >70%, which is comparable to that of the reference compound, 1 (≥80%) ( Table 1). These six compounds were tested for their intrinsic antibacterial activity.…”

mentioning

confidence: 89%

Ligand Promiscuity between the Efflux Pumps Human P-Glycoprotein and S. aureus NorA

Brincat

Broccatelli

Sabatini

et al. 2012

ACS Med. Chem. Lett.

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Thirty-two diverse compounds were evaluated for their ability to inhibit both Pgp-mediated efflux in mouse T-lymphoma L5178 MDR1 and NorA-mediated efflux in S. aureus SA-1199B. Only four compounds were strong inhibitors of both efflux pumps. Three compounds were found to inhibit Pgp exclusively and strongly, while seven compounds inhibited only NorA. These results demonstrate that Pgp and NorA inhibitors do not necessarily overlap, opening the way to safer therapeutic use of effective NorA inhibitors.

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mentioning

confidence: 89%

Ligand Promiscuity between the Efflux Pumps Human P-Glycoprotein and S. aureus NorA

Brincat

Broccatelli

Sabatini

et al. 2012

ACS Med. Chem. Lett.

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“…Permeability changes occur either via decreased permeability of the hydrophilic pores (OMP) or through alteration of the active transport (efflux) pump (Kaatz et al, 1991), thereby decreasing the intracellular content of fluoroquinolones. The enzymes that degrade quinolone antibacterial agents have not been observed.…”

Section: Bacterial Resistancementioning

confidence: 99%

Quinolones: a class of antimicrobial agents

Sárközy¹

2001

Vet. Med. - Czech

119

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ABSTRACT:The fluoroquinolones are a series of synthetic antibacterial agents that are used in the treatment of a variety of bacterial infections. These agents inhibit the DNA gyrase, abolishing its activity by interfering with the DNA-rejoining reaction. The inhibition of the resealing leads to the liberation of fragments that are subsequently destroyed by the bacterial exonucleases. All fluoroquinolones accumulate within bacteria very rapidly, so that a steady-state intrabacterial concentration is obtained within a few minutes. Resistance develops slowly and is usually chromosomal and not plasmid mediated. However, development of resistance and transfer between animal and human pathogens has become a fervently argued issue among the microbiologists. Another concern regarding the use of new quinolones in the veterinary field is a possible detrimental effect on the environment. It still seems unlikely that the controlled use of veterinary quinolones will give rise to unfavorable effects on the environment.

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“…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]. The concentrations of quinolones at which resistant mutants of bacteria can be isolated in vitro are 8-16-fold lower than the MIC's for quinolones after subcultivation of these mutants [6].…”

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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Mechanisms of Fluoroquinolone Resistance in Staphylococcus aureus

Cited by 132 publications

References 25 publications

Ligand Promiscuity between the Efflux Pumps Human P-Glycoprotein and S. aureus NorA

Ligand Promiscuity between the Efflux Pumps Human P-Glycoprotein and S. aureus NorA

Quinolones: a class of antimicrobial agents

Occurrence of quinolone resistance inStaphylococcus aureusfrom nosocomial infection

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