PMID:20660686

Citation	Singh, R, Ledesma, KR, Chang, KT and Tam, VH (2010) Impact of recA on levofloxacin exposure-related resistance development.Antimicrob. Agents Chemother. 54:4262-8
Abstract	Genetic mutations are one of the major mechanisms by which bacteria acquire drug resistance. One of the known mechanisms for inducing mutations is the SOS response system. We investigated the effect of disrupting recA, an inducer of the SOS response, on resistance development using an in vitro hollow-fiber infection model. A clinical Staphylococcus aureus isolate and a laboratory wild-type strain of Escherichia coli were compared to their respective recA-deleted isogenic daughter isolates. Approximately 2 × 10(5) CFU/ml of bacteria were subjected to escalating levofloxacin exposures for up to 120 h. Serial samples were obtained to ascertain simulated drug exposures and total and resistant bacterial burdens. Quinolone resistance determining regions of gyrA and grlA (parC for E. coli) in levofloxacin-resistant isolates were sequenced to confirm the mechanism of resistance. The preexposure MICs of the recA-deleted isolates were 4-fold lower than those of their respective parents. In S. aureus, a lower area under the concentration-time curve over 24 h at steady state divided by the MIC (AUC/MIC) was required to suppress resistance development in the recA-deleted mutant (an AUC/MIC of >23 versus an AUC/MIC of >32 was necessary in the mutant versus the parent isolate, respectively), and a prominent difference in the total bacterial burden was observed at 72 h. Using an AUC/MIC of approximately 30, E. coli resistance emergence was delayed by 24 h in the recA-deleted mutant. Diverse mutations in gyrA were found in levofloxacin-resistant isolates recovered. Disruption of recA provided additional benefits apart from MIC reduction, attesting to its potential role for pharmacologic intervention. The clinical relevance of our findings warrants further investigations.
Links	PubMed Online version:10.1128/AAC.00168-10
Keywords	Anti-Bacterial Agents; Bacterial Proteins; Chromatography, High Pressure Liquid; Escherichia coli; Microbial Sensitivity Tests; Mutation; Ofloxacin; Rec A Recombinases; Staphylococcus aureus
edit table

Main Points of the Paper

Please summarize the main points of the paper.

Materials and Methods Used

Please list the materials and methods used in this paper (strains, plasmids, antibodies, etc).

Phenotype Annotations

See Help:AnnotationTable for details on how to edit this table.
<protect>

Phenotype of	Taxon Information	Genotype Information (if known)	Condition Information	OMP ID	OMP Term Name	ECO ID	ECO Term Name	Notes	Status
a mutation or genetic difference within a strain	Taxon: Escherichia coli Strain: K-12 Substrain: MG1655 relA(del) NCBI Taxon ID: 83333	Genotype of Reference Strain: recA+ Genotype of Experimental Strain : recA(del)	Reference Condition:	OMP:0006040	decreased resistance to quinolone	ECO:0000016	loss-of-function mutant phenotype evidence	The recA(del) mutation reduced the MIC of levofloxacin (CHEBI:63598) to 25% that of the recA+ parent (described in text).
a mutation or genetic difference within a strain	Taxon: Escherichia coli Strain: K-12 Substrain: MG1655 NCBI Taxon ID: 83333	Genotype of Reference Strain: recA+ Genotype of Experimental Strain : recA(del)	Reference Condition:			ECO:0000016	loss-of-function mutant phenotype evidence	The recA(del) mutation delays the regrowth and emergence of resistant mutants by 24 h in a hollow-fiber infection model (Fig. 4).
edit table

</protect>

References

See Help:References for how to manage references in omp dev.