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.

Serum Differentially Alters the Antifungal Properties of Echinocandin Drugs

Abstract: Antifungal efficacies of the echinocandin drugs caspofungin, micafungin, and anidulafungin were reduced significantly in the presence of 50% human serum, which yielded nearly equivalent MICs or minimum effective concentrations against diverse Candida spp. and Aspergillus spp. Consistent with a direct drug interaction, serum decreased the sensitivity of glucan synthase to echinocandin drugs.

Establishing In Vitro-In Vivo Correlations for Aspergillus fumigatus: the Challenge of Azoles versus Echinocandins

Abstract: Two clinical isolates of Aspergillus fumigatus, designated AT and DK, were recently obtained from patients failing caspofungin and itraconazole therapy, respectively. The isolates were tested by microdilution for susceptibility to itraconazole, voriconazole, posaconazole, ravuconazole, and caspofungin and by Etest for susceptibility to amphotericin B and caspofungin. Susceptibility testing documented that the DK isolate was azole resistant (itraconazole and posaconazole MICs, >4 microg/ml; voriconazole MIC, 2 microg/ml; ravuconazole MIC, 4 microg/ml), and the resistance was confirmed in a hematogenous mouse model, with mortality and the galactomannan index as the primary and secondary end points. Sequencing of the cyp51A gene revealed the M220K mutation, conferring multiazole resistance. The Etest, but not microdilution, suggested that the AT isolate was resistant to caspofungin (MIC, >32 microg/ml). In the animal model, this isolate showed reduced susceptibility to caspofungin. Sequencing of the FKS1 gene revealed no mutations; the enzyme retained full sensitivity in vitro; and investigation of the polysaccharide composition showed that the beta-(1,3)-glucan proportion was unchanged. However, gene expression profiling by Northern blotting and real-time PCR demonstrated that the FKS gene was expressed at a higher level in the AT isolate than in the susceptible control isolate. To our knowledge, this is the first report to document the presence of multiazole-resistant clinical isolates in Denmark and to demonstrate reduced susceptibility to caspofungin in a clinical A. fumigatus isolate with increased expression of the FKS gene. Further research to determine the prevalence of resistance in A. fumigatus worldwide, and to develop easier and reliable tools for the identification of such isolates in routine laboratories, is warranted.

Sequence and transcription mapping of Bacillus subtilis competence genes comB and comA, one of which is related to a family of bacterial regulatory determinants.

Abstract: The complete nucleotide sequences of the comA and comB loci of Bacillus subtilis were determined. The products of these genes are required for the development of competence in B. subtilis and for the expression of late-expressing competence genes. The major 5' termini of both the comA and comB transcripts were determined. The inferred promoters of both comA and comB contained sequences that were similar to those found at the -10 and -35 regions of promoters that are used by sigma A-RNA polymerase, the primary form of this enzyme in vegetative cells. The comB gene was located approximately 3 kilobase pairs upstream of the comA gene and encoded a 409-amino-acid protein with a predicted molecular weight of 46,693. The comA locus contained two open reading frames (ORFs) and comB contained one ORF. The predicted amino acid sequence of the comA ORF1 gene product consisted of 214 amino acids, with an aggregate molecular weight of 24,132. The ORF1 product was required for competence, while ORF2, which was cotranscribed with ORF1 and encoded a predicted protein of 126 amino acids, was not. The predicted protein sequence of the comA ORF1 gene product was found to be similar to that of several members of the effector class of procaryotic signal transducers. The C-terminal portion of the predicted comA sequence contained a possible helix-turn-helix motif, which is characteristic of DNA-binding proteins. comA ORF1 was cloned on a multicopy plasmid and was shown to complement the competence-deficient phenotype caused by the comA124 insertion of Tn917lac. Also, the presence of comA ORF1 in multiple copies interfered with sporulation. Anti-peptide antibodies raised to the predicted product of comA ORF1 reacted strongly with a single protein band of about 24,000 daltons in immunoblots. The possible roles of multiple signal transduction systems in triggering the development of competence are discussed.

Mesoporous silica nanoparticles inhibit cellular respiration.

Abstract: We studied the effect of two types of mesoporous silica nanoparticles, MCM-41 and SBA-15, on mitochondrial O2 consumption (respiration) in HL-60 (myeloid) cells, Jurkat (lymphoid) cells, and isolated mitochondria. SBA-15 inhibited cellular respiration at 25–500 µg/mL; the inhibition was concentration-dependent and time-dependent. The cellular ATP profile paralleled that of respiration. MCM-41 had no noticeable effect on respiration rate. In cells depleted of metabolic fuels, 50 µg/mL SBA-15 delayed the onset of glucose-supported respiration by 12 min and 200 µg/mL SBA-15 by 34 min; MCM-41 also delayed the onset of glucose-supported respiration. Neither SBA-15 nor MCM-41 affected cellular glutathione. Both nanoparticles inhibited respiration of isolated mitochondria and submitochondrial particles.