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Mutant Selection Window in Levofloxacin and Moxifloxacin Treatments of Experimental Pneumococcal Pneumonia in a Rabbit Model of Human Therapy. Delphine Croisier, 2004.For some pneumococci the fluoroquinolone MICs are low but the mutant prevention concentrations (MPCs) are high; this difference defines in vitro the mutant selection window (MSW) . We investigated in vivo the bacterial reduction and the occurrence of resistant mutants with moxifloxacin (MFX; 400 mg once daily) or levofloxacin (LVX; 500 mg twice daily) in treatments similar to those in humans with experimental pneumonia due to pneumococci (expPP) exhibiting various MICs and MPCs . The MIC/MPC for MFX and LVX and genotypes were as follows: strain 16089, 0.125/0.125 and 0.5/0.5 (wild type); strain MS1A, 0.25/0.25 and 1/2 (efflux); strain MS2A, 0.25/4 and 1.75/28 (parC79); strain MR3B4, 0.25/4 and 2/32 (parC79); strain M16, 0.5/2 and 8/32 (parC83); strain Gyr-1207, 1.5/3 and 8/16 (gyrA); and strain MQ3A, 4/4 and 16/64 (parC and gyrA) . Both drugs were efficient with wild type-expPP, but only MFX was efficient with efflux-expPP . No bacterial reduction was observed for parC-expPPs due to mutants observed in 18 to 100% of animals, depending on the strain and the drug tested . These mutants showed unbound area under the concentration-time curve and MICs of from 50 to 164 for MFX . The in vivo pharmacodynamic boundaries of the MSW were different for MFX and LVX . We conclude that, after LVX or MFX treatment, mutants occur in vivo if there is a preexisting parC mutation, since the drug concentrations fall below the MPCs of these strains . Since the MPC determination cannot be routinely determined, these phenotypes or genotypes should be detected by simple tests to guide the therapeutic options . Aquatic Snails, Passive Hosts of Mycobacterium ulcerans. Laurent Marsollier, 2004. Molecular Characterization of CcpA and Involvement of This Protein in Transcriptional Regulation of Lactate Dehydrogenase and Pyruvate Formate-Lyase in the Ruminal Bacterium Streptococcus bovis. Narito Asanuma, 2004.A ccpA gene that encodes global catabolite control protein A (CcpA) in Streptococcus bovis was identified and characterized, and the involvement of CcpA in transcriptional control of a gene (ldh) encoding lactate dehydrogenase (LDH) and a gene (pfl) encoding pyruvate formate-lyase (PFL) was examined . The ccpA gene was shown to be transcribed as a monocistronic operon . A catabolite-responsive element (cre) was found in the promoter region of ccpA, suggesting that ccpA transcription in S . bovis is autogenously regulated . CcpA required HPr that was phosphorylated at the serine residue at position 46 (HPr-[Ser-P]) for binding to the cre site, but glucose 6-phosphate, fructose 1,6-bisphosphate, and NADP had no effect on binding . Diauxic growth was observed when S . bovis was grown in a medium containing glucose and lactose, but it disappeared when ccpA was disrupted, which indicates that CcpA is involved in catabolite repression in S . bovis . The level of ccpA mRNA was higher when cells were grown on glucose than when they were grown on lactose, which was in line with the level of ldh mRNA . When cells were grown on glucose, the ldh mRNA level was lower but the pfl mRNA level was higher in a ccpA-disrupted mutant than in the parent strain, which suggests that ldh transcription is enhanced and pfl transcription is suppressed by CcpA . The ccpA-disrupted mutant produced less lactate and more formate than the parent, probably because the mutant had reduced LDH activity and elevated PFL activity . In the upper region of both ldh and pfl, a cre-like sequence was found, suggesting that the complex consisting of CcpA and HPr-[Ser-P] binds to the possible cre sites . Thus, CcpA appears to be involved in the global regulation of sugar utilization in S . bovis . A Turquoise Mutant Genetically Separates Expression of Genes Encoding Phycoerythrin and Its Associated Linker Peptides. Laura Ort Seib, 2002.During complementary chromatic adaptation (CCA), cyanobacterial light harvesting structures called phycobilisomes are restructured in response to ambient light quality shifts . Transcription of genes encoding components of the phycobilisome is differentially regulated during this process: red light activates cpcB2A2, whereas green light coordinately activates the cpeCDE and cpeBA operons . Three signal transduction components that regulate CCA have been isolated to date: a sensor-photoreceptor (RcaE) and two response regulators (RcaF and RcaC) . Mutations in the genes encoding these components affect the accumulation of both cpcB2A2 and cpeBA gene products . We have isolated and characterized a new pigmentation mutant called Turquoise 1 . We demonstrate that this mutant phenotype is due to a dramatic decrease in cpeBA transcript abundance and results from a lesion in the cpeR gene . However, in this mutant cpeCDE RNA levels remain near those found in wild-type cells . Our results show that the coordinate regulation of cpeBA and cpeCDE by green light can be uncoupled by the loss of CpeR, and we furnish the first genetic evidence that different regulatory mechanisms control these two operons . Sequence analysis of CpeR reveals that it shares limited sequence similarity to members of the PP2C class of protein serine/threonine phosphatases . We also demonstrate that cpeBA and cpeCDE retain light quality responsiveness in a mutant lacking the RcaE photoreceptor . This provides compelling evidence for the partial control of CCA through an as-yet-uncharacterized second light quality sensing system .
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