Gastrointestinal symptoms are commonly reported in as much as 65% of people with CF even independent of pancreatic enzyme replacement therapy (PERT) and the most frequent of these symptoms are bloating/distension, flatulence, abdominal pain and bowel habit changes. An alteration in the intestinal microbiome due to intestinal dysmotility, inflammation or other changes including pH changes in the intestine related to CFTR gene mutation may cause intestinal dysbiosis leading to a bacterial overgrowth in the proximal small intestine which may explain some of the findings of distension and bloating in CF.
Our small pilot study aims to investigate use of the only FDA-approved antibiotic, rifaximin for a GI syndrome- IBS, to treat bloating and global GI symptoms in CF patients with bloating and distension. Our goal is to recruit patients >12 years and age/sex matched into rifaximin and placebo arms with total of 100 recruited subjects recruited.

开始日期2024-11-01

申办/合作机构

Wake Forest School of Medicine

[+3]

NCT06483737 / Not yet recruitingN/AIIT

Human Albumin Infusion in Liver Cirrhosis and Overt Hepatic Encephalopathy (HACHE): an Invesitgator-initiated, Open-label, Multicenter, Randomized Controlled Trial

Hepatic encephalopathy (HE), a severe complication of decompensated cirrhosis, is characterized as neurocognitive dysfunction. Emerging evidence suggests the potential role of human albumin infusion for the treatment of HE, but its optimal dosage remains undefined. Therefore, the investigators planned a randomized controlled trial (RCT) to compare the efficacy of human albumin infusion at different dosages in in patients with liver cirrhosis and overt HE.

开始日期2024-10-01

申办/合作机构

中国人民解放军北部战区总医院

NCT06652087 / RecruitingN/AIIT

The Effect of Correction of Bacterial Overgrowth Syndrome in the Small Intestine on Cardiac Function in Patients with Heart Failure with Preserved Ejection Fraction

Single-center, double-blind, randomized, controlled intervention study of the effect of correction of bacterial overgrowth syndrome in the small intestine (SIBO) on cardiac function in patients with heart failure with preserved ejection fraction (HFpEF) (SIBO-HFpEF). The aim of the study is to evaluate the efficacy and safety of rifaximin in patients with HFpEF and SIBO.

开始日期2024-09-02

申办/合作机构

I.M. Sechenov First Moscow State Medical University

100 项与 Bacterial RNAP 相关的临床结果

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100 项与 Bacterial RNAP 相关的转化医学

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0 项与 Bacterial RNAP 相关的专利（医药）

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项与 Bacterial RNAP 相关的文献（医药）

2015-12-01·Antimicrobial Agents and Chemotherapy2区 · 医学

Fitness Cost of Rifampin Resistance in Neisseria meningitidis: In Vitro Study of Mechanisms Associated with rpoB H553Y Mutation

2区 · 医学

Article

作者: Pagliuca, Chiara ; Bucci, Cecilia ; Alifano, Pietro ; Pastore, Gabiria ; Colicchio, Roberta ; Salvatore, Paola ; Sammartino, Josè Camilla ; Talà, Adelfia ; Scaglione, Elena ; Cicatiello, Annunziata Gaetana ; Pagliarulo, Caterina

ABSTRACT Rifampin chemoprophylaxis against Neisseria meningitidis infections led to the onset of rifampin resistance in clinical isolates harboring point mutations in the rpoB gene, coding for the RNA polymerase β chain. These resistant strains are rare in medical practice, suggesting their decreased fitness in the human host. In this study, we isolated rifampin-resistant rpoB mutants from hypervirulent serogroup C strain 93/4286 and analyzed their different properties, including the ability to grow/survive in different culture media and in differentiated THP-1 human monocytes and to compete with the wild-type strain in vitro . Our results demonstrate that different rpoB mutations (H553Y, H553R, and S549F) may have different effects, ranging from low- to high-cost effects, on bacterial fitness in vitro . Moreover, we found that the S549F mutation confers temperature sensitivity, possibly explaining why it is observed very rarely in clinical isolates. Comparative high-throughput RNA sequencing analysis of bacteria grown in chemically defined medium demonstrated that the low-cost H553Y substitution resulted in global transcriptional changes that functionally mimic the stringent response. Interestingly, many virulence-associated genes, including those coding for meningococcal type IV pili, porin A, adhesins/invasins, IgA protease, two-partner secretion system HrpA/HrpB, enzymes involved in resistance to oxidative injury, lipooligosaccharide sialylation, and capsular polysaccharide biosynthesis, were downregulated in the H553Y mutant compared to their level of expression in the wild-type strain. These data might account for the reduced capacity of this mutant to grow/survive in differentiated THP-1 cells and explain the rarity of H553Y mutants among clinical isolates.

2015-05-01·Journal of Biotechnology3区 · 工程技术

Rifampicin-resistance, rpoB polymorphism and RNA polymerase genetic engineering

3区 · 工程技术

Review

作者: Pasanisi, Daniela ; Palumbo, Carla ; Talà, Adelfia ; Alifano, Pietro

Following its introduction in 1967, rifampicin has become a mainstay of therapy in the treatment of tuberculosis, leprosy and many other widespread diseases. Its potent antibacterial activity is due to specific inhibition of bacterial RNA polymerase. However, resistance to rifampicin was reported shortly after its introduction in the medical practice. Studies in the model organism Escherichia coli helped to define the molecular mechanism of rifampicin-resistance demonstrating that resistance is mostly due to chromosomal mutations in rpoB gene encoding the RNA polymerase β chain. These studies also revealed the amazing potential of the molecular genetics to elucidate the structure-function relationships in bacterial RNA polymerase. The scope of this paper is to illustrate how rifampicin-resistance has been recently exploited to better understand the regulatory mechanisms that control bacterial cell physiology and virulence, and how this information has been used to maneuver, on a global scale, gene expression in bacteria of industrial interest. In particular, we reviewed recent literature regarding: (i) the effects of rpoB mutations conferring rifampicin-resistance on transcription dynamics, bacterial fitness, physiology, metabolism and virulence; (ii) the occurrence in nature of "mutant-type" or duplicated rifampicin-resistant RNA polymerases; and (iii) the RNA polymerase genetic engineering method for strain improvement and drug discovery.

2013-01-15·Journal of Bacteriology3区 · 生物学

High-Mobility-Group A-Like CarD Binds to a DNA Site Optimized for Affinity and Position and to RNA Polymerase To Regulate a Light-Inducible Promoter in Myxococcus xanthus

3区 · 生物学

Article

作者: Murillo, Francisco J. ; Padmanabhan, S. ; García-Heras, Francisco ; Elías-Arnanz, Montserrat ; Abellón-Ruiz, Javier

ABSTRACTThe CarD-CarG complex controls various cellular processes in the bacteriumMyxococcus xanthusincluding fruiting body development and light-induced carotenogenesis. The CarD N-terminal domain, which defines the large CarD_CdnL_TRCF protein family, binds to CarG, a zinc-associated protein that does not bind DNA. The CarD C-terminal domain resembles eukaryotic high-mobility-group A (HMGA) proteins, and its DNA binding AT hooks specifically recognize the minor groove of appropriately spaced AT-rich tracts. Here, we investigate the determinants of the only known CarD binding site, the one crucial in CarD-CarG regulation of the promoter of thecarQRSoperon (PQRS), a light-inducible promoter dependent on the extracytoplasmic function (ECF) σ factor CarQ.In vitro, mutating either of the 3-bp AT tracts of this CarD recognition site (TTTCCAGAGCTTT) impaired DNA binding, shifting the AT tracts relative to PQRShad no effect or marginally lowered DNA binding, and replacing the native site by the HMGA1a binding one at the human beta interferon promoter (with longer AT tracts) markedly enhanced DNA binding.In vivo, however, all of these changes deterred PQRSactivation in wild-typeM. xanthus, as well as in a strain with the CarD-CarG pair replaced by theAnaeromyxobacter dehalogenansCarD-CarG (CarDAd-CarGAd). CarDAd-CarGAdis functionally equivalent to CarD-CarG despite the lower DNA binding affinityin vitroof CarDAd, whose C-terminal domain resembles histone H1 rather than HMGA. We show that CarD physically associates with RNA polymerase (RNAP) specifically via interactions with the RNAP β subunit. Our findings suggest that CarD regulates a light-inducible, ECF σ-dependent promoter by coupling RNAP recruitment and binding to a specific DNA site optimized for affinity and position.