Public Health Research Institute

About: Public Health Research Institute is a based out in . It is known for research contribution in the topics: Population & Randomized controlled trial. The organization has 4889 authors who have published 8149 publications receiving 276945 citations.

A temporal signal, independent of agr, is required for hla but not spa transcription in Staphylococcus aureus.

Abstract: Staphylococcus aureus exoprotein expression is controlled by a global regulon known as agr. This system activates transcription of some target genes and represses transcription of others. Target genes expressed postexponentially such as alpha-hemolysin (hla) are activated by agr; target genes expressed during exponential phase such as protein A (spa) are repressed by agr. A unique feature of the agr system is that this transcriptional regulation is mediated by a 517-nucleotide transcript, RNAIII. While it is clear that agr differentially regulates the expression of exponential and postexponential exoproteins, the precise role of agr in the temporal control of these events has not yet been explored. In this report, we examine the effects of expressing RNAIII, the agr regulator, under the control of the inducible beta-lactamase (bla) promoter at different times in the growth cycle. We confirm previous results showing that agr is required for postexponential-phase expression of hla and further show that a separate postexponential-phase signal independent of agr function is also needed for activation of hla transcription. We also show that in an agr mutant transcription of spa occurs throughout the growth cycle, is inhibited immediately upon induction of RNAIII, and is thus indifferent to the postexponential signal required for hla activation. Images

Breakthrough Invasive Candidiasis in Patients on Micafungin

Abstract: For Candida species, a bimodal wild-type MIC distribution for echinocandins exists, but resistance to echinocandins is rare. We characterized isolates from patients with invasive candidiasis (IC) breaking through ≥3 doses of micafungin therapy during the first 28 months of its use at our center: MICs were determined and hot-spot regions within FKS genes were sequenced. Eleven of 12 breakthrough IC cases identified were in transplant recipients. The median duration of micafungin exposure prior to breakthrough was 33 days (range, 5 to 165). Seventeen breakthrough isolates were recovered: FKS hot-spot mutations were found in 5 C. glabrata and 2 C. tropicalis isolates; of these, 5 (including all C. glabrata isolates) had micafungin MICs of >2 μg/ml, but all demonstrated caspofungin MICs of >2 μg/ml. Five C. parapsilosis isolates had wild-type FKS sequences and caspofungin MICs of 0.5 to 1 μg/ml, but 4/5 had micafungin MICs of >2 μg/ml. The remaining isolates retained echinocandin MICs of ≤2 μg/ml and wild-type FKS gene sequences. Breakthrough IC on micafungin treatment occurred predominantly in severely immunosuppressed patients with heavy prior micafungin exposure. The majority of cases were due to C. glabrata with an FKS mutation or wild-type C. parapsilosis with elevated micafungin MICs. MIC testing with caspofungin identified all mutant strains. Whether the naturally occurring polymorphism within the C. parapsilosis FKS1 gene responsible for the bimodal wild-type MIC distribution is also responsible for micafungin MICs of >2 μg/ml and clinical breakthrough or an alternative mechanism contributes to the nonsusceptible echinocandin MICs in C. parapsilosis requires further study.

ComA, a phosphorylated response regulator protein of Bacillus subtilis, binds to the promoter region of srfA.

Abstract: ComA is a response regulator protein of Bacillus subtilis which is required for the transcription of several genes which are involved in late-growth expression and in responses to environmental stress. Among these genes are degQ, gsiA, and srfA. The last is an operon needed for the development of genetic competence, surfactin production, and normal sporulation. We show here that partially purified ComA protein, isolated from an overproducing Escherichia coli strain, is phosphorylated in vitro by incubation with acetyl phosphate and that ComA could bind specifically to a DNA fragment containing the promoter of srfA and associated sequences. The binding affinity is enhanced when ComA is phosphorylated. DNase I protection analysis identified two protected sites located upstream from the srfA promoter. The presence of DNase I-hypersensitive bonds induced by ComA binding which are located between the protected sequences is consistent with a model for ComA action involving the bending of DNA.