University of North Texas Health Science Center

About: University of North Texas Health Science Center is a education organization based out in Fort Worth, Texas, United States. It is known for research contribution in the topics: Population & Receptor. The organization has 2972 authors who have published 5401 publications receiving 153180 citations. The organization is also known as: UNT Health Science Center & UNTHSC.

The product of the pleiotropic Escherichia coli gene csrA modulates glycogen biosynthesis via effects on mRNA stability.

Abstract: The carbon storage regulator gene, csrA, modulates the expression of genes in the glycogen biosynthesis and gluconeogenesis pathways in Escherichia coli and has been cloned, mapped and sequenced (T. Romeo, M. Gong, M.Y. Liu, and A.M. Brun-Zinkernagel, J. Bacteriol. 175:4744-4755, 1993; T. Romeo and M. Gong, J. Bacteriol. 175:5740-5741, 1993). We have now conducted experiments that begin to elucidate a unique mechanism for csrA-mediated regulation. Steady-state levels of glgC transcripts, encoding ADP-glucose pyrophosphorylase, were elevated by up to sixfold in a csrA::kanR mutant and were less than 6.5% of wild-type levels in a strain containing pCSR10 (csrA+), as shown by S1 nuclease protection analysis. The rate of chemical decay of these transcripts after adding rifampin to cultures was dramatically reduced by the csrA::kanR mutation. Deletion studies of a glgC'-'lacZ translational fusion demonstrated that the region surrounding the initiation codon was important for csrA-mediated regulation and indicated that neither csrA-mediated regulation nor stationary phase induction of glgC expression originates at the level of transcript initiation. Cell-free (S-200) extracts containing the CsrA gene product potently and specifically inhibited the in vitro transcription-translation of glg genes. The deduced amino acid sequence of CsrA was found to contain the KH motif, which characterizes a subset of diverse RNA-binding proteins. The results indicate that CsrA accelerates net 5'-to-3' degradation of glg transcripts, potentially through selective RNA binding.

Meta-analysis: the efficacy, adverse events, and adherence related to first-line anti-Helicobacter pylori quadruple therapies

Abstract: Summary Background : Owing to rising drug-resistant Helicobacter pylori infections, currently recommended proton-pump inhibitor-based triple therapies are losing their efficacy, and regimens efficacious in the presence of drug resistance are needed. Aims : To summarize the efficacy, safety and adherence of first-line quadruple H. pylori therapies in adults. Methods : Meta-regression models identified factors explaining variation in the efficacy of first-line quadruple therapies from 145 treatment arms. Estimates of average efficacy were calculated within homogeneous groups. Results : Quadruple therapy containing a gastric acid inhibitor, bismuth, metronidazole and tetracycline was enhanced when omeprazole was included, treatment duration lasted 10–14 days, and when therapy took place in the Netherlands, Hong Kong and Australia. Treatment efficacy decreased as the prevalence of metronidazole resistance increased. Even in areas with a high prevalence of metronidazole resistance, this quadruple regimen eradicated more than 85% of H. pylori infections when it contained omeprazole and was given for 10–14 days. Furthermore, in the presence of clarithromycin resistance, this quadruple regimen eradicated 90–100% of H. pylori infections, while the currently recommended triple therapy containing clarithromycin, amoxicillin and a proton-pump inhibitor eradicated only 25–61% (P < 0.001). Adherence and adverse events for quadruple therapy were similar to currently recommended triple therapies. Conclusions : Guidelines should include quadruple therapy with a proton-pump inhibitor, a bismuth compound, metronidazole and tetracycline among recommended first-line anti-H. pylori therapies.

Can Ceftazidime-Avibactam and Aztreonam Overcome β-Lactam Resistance Conferred by Metallo-β-Lactamases in Enterobacteriaceae?

Abstract: Based upon knowledge of the hydrolytic profile of major β-lactamases found in Gram-negative bacteria, we tested the efficacy of the combination of ceftazidime-avibactam (CAZ-AVI) with aztreonam (ATM) against carbapenem-resistant enteric bacteria possessing metallo-β-lactamases (MBLs). Disk diffusion and agar-based antimicrobial susceptibility testing were initially performed to determine the in vitro efficacy of a unique combination of CAZ-AVI and ATM against 21 representative Enterobacteriaceae isolates with a complex molecular background that included blaIMP, blaNDM, blaOXA-48, blaCTX-M, blaAmpC, and combinations thereof. Time-kill assays were conducted, and the in vivo efficacy of this combination was assessed in a murine neutropenic thigh infection model. By disk diffusion assay, all 21 isolates were resistant to CAZ-AVI alone, and 19/21 were resistant to ATM. The in vitro activity of CAZ-AVI in combination with ATM against diverse Enterobacteriaceae possessing MBLs was demonstrated in 17/21 isolates, where the zone of inhibition was ≥21 mm. All isolates demonstrated a reduction in CAZ-AVI agar dilution MICs with the addition of ATM. At 2 h, time-kill assays demonstrated a ≥4-log10-CFU decrease for all groups that had CAZ-AVI with ATM (8 μg/ml) added, compared to the group treated with CAZ-AVI alone. In the murine neutropenic thigh infection model, an almost 4-log10-CFU reduction was noted at 24 h for CAZ-AVI (32 mg/kg every 8 h [q8h]) plus ATM (32 mg/kg q8h) versus CAZ-AVI (32 mg/kg q8h) alone. The data presented herein require us to carefully consider this new therapeutic combination to treat infections caused by MBL-producing Enterobacteriaceae.