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.

Regulation of the β-Glucoside System in Escherchia coli K-12

Abstract: In Escherichia coli wild-type cells, a mutation at the beta-glucoside regulatory gene (bglR(+) to bglR(-)) leads to simultaneous expression of inducible phospho-beta-glucosidase B (bglB(+)) and a beta-glucoside-specific species of enzyme II (beta-glucoside transport I [bglC(+)]); an additional mutation (bglS(+) to bglS4) allows these enzymes to be formed constitutively. The bgl alleles have been mapped in the following order: pyrE, bglA, bglB, bglS, bglR, bglC, ilvD. The back mutation in the regulatory allele (bglR(-) to bglR(+)) caused the cessation of the expression of the bglB(+), bglS(+) or bglS4, bglC(+) alleles. However, a mutation in a strain with bglB(+), bglS4, bglR8, bglC(+) alleles, at the ini site that lies between the bglS4 and the bglR8 allele, allowed the expression of the bglS4 and bglB(+) alleles, but showed no affect on the expression of the bglC(+) allele. It is suggested that the ini mutation possesses a promotor-type function that in the absence of regulatory allele function (bglR8) renews the functioning of only the bglS4 and bglB(+) alleles. The complementation studies have shown that the bglB(+), bglS(+) or bglS4, bglC(+) alleles are expressed only in cis to the bglR(-) allele. In the constitutive strain (bglB(+), bglS4, bglR(-), bglC(+)), the expressed bglS4 allele formed a soluble product that acts in trans over the bglB(+) and bglC(+) alleles and that appears effective only when the bglB(+) and the bglC(+) alleles are expressed in cis to the bglR(-) allele. It thus showed that the constitutive biosynthesis of phospho-beta-glucosidase B and beta-glucoside transport I is under positive control. Since the regulatory allele bglR(-) lies between the bglS4 and the blgC(+) alleles, and acts in cis, it appears that the mutation (bglR(+) to bglR(-)) allows the initiation of transcription in one direction to express the bglS4, bglB(+) alleles and in the other to express the bglC(+) allele. The structural genes bglB and bglC lie adjacent to the regulatory genes bglR and bglS, and the structural genes are coordinately controlled by the regulatory genes. It is, therefore, proposed that the bglB, bglS, bglR, bglC genes form a bgl operon.

In vitro cross-resistance to daptomycin and host defense cationic antimicrobial peptides in clinical methicillin-resistant Staphylococcus aureus isolates.

Abstract: We investigated the hypothesis that methicillin-resistant Staphylococcus aureus (MRSA) isolates developing reduced susceptibilities to daptomycin (DAP; a calcium-dependent molecule acting as a cationic antimicrobial peptide [CAP]) may also coevolve reduced in vitro susceptibilities to host defense cationic antimicrobial peptides (HDPs). Ten isogenic pairs of clinical MRSA DAP-susceptible/DAP-resistant (DAPs/DAPr) strains were tested against two distinct HDPs differing in structure, mechanism of action, and origin (thrombin-induced platelet microbicidal proteins [tPMPs] and human neutrophil peptide-1 [hNP-1]) and one bacterium-derived CAP, polymyxin B (PMB). Seven of 10 DAPr strains had point mutations in the mprF locus (with or without yyc operon mutations), while three DAPr strains had neither mutation. Several phenotypic parameters previously associated with DAPr were also examined: cell membrane order (fluidity), surface charge, and cell wall thickness profiles. Compared to the 10 DAPs parental strains, their respective DAPr strains exhibited (i) significantly reduced susceptibility to killing by all three peptides (P < 0.05), (ii) increased cell membrane fluidity, and (iii) significantly thicker cell walls (P < 0.0001). There was no consistent pattern of surface charge profiles distinguishing DAPs and DAPr strain pairs. Reduced in vitro susceptibility to two HDPs and one bacterium-derived CAP tracked closely with DAPr in these 10 recent MRSA clinical isolates. These results suggest that adaptive mechanisms involved in the evolution of DAPr also provide MRSA with enhanced survivability against HDPs. Such adaptations appear to correlate with MRSA variations in cell membrane order and cell wall structure. DAPr strains with or without mutations in the mprF locus demonstrated significant cross-resistance profiles to these unrelated CAPs.