Rifamycins, a group of bacterial RNA polymerase inhibitors, are the firstline antimicrobial drugs to treat tuberculosis. In light of the emergence of rifamycinresistant bacteria, development of new RNA polymerase inhibitors that kill rifamycinresistant bacteria with high bioavailability is urgent. Structural analysis of bacterial RNA polymerase in complex with inhibitors by crystallography and cryo-EM indicates that RNA polymerase inhibitors function through five distinct molecular mechanisms:inhibition of the extension of short RNA; competition with substrates; inhibition of the conformational change of the'bridge helix'; inhibition of clamp opening;inhibition of clamp closure. This article reviews the research progress of these five groups of RNA polymerase inhibitors to provide references for the modification of existing RNA polymerase inhibitors and the discovery of new RNA polymerase inhibitors.
Antitubercular Agents ; therapeutic use ; Bacteria ; drug effects ; enzymology ; DNA-Directed RNA Polymerases ; metabolism ; Drug Discovery ; trends ; Drug Resistance, Bacterial ; Enzyme Activation ; drug effects ; Enzyme Inhibitors ; pharmacology ; Humans ; RNA, Bacterial ; Tuberculosis ; drug therapy ; enzymology

Bacterial Proteins ; genetics ; metabolism ; Biofilms ; DNA-Binding Proteins ; genetics ; metabolism ; Flagella ; genetics ; metabolism ; Gene Expression Regulation, Bacterial ; Transcription Factors ; genetics ; metabolism ; Vibrio parahaemolyticus ; cytology ; genetics ; growth & development ; physiology

Fluoroquinolone (FQ) antibiotics are an important class of synthetic antibacterial agents. These are the most extensively used drugs for treating bacterial infections in the field of both human and veterinary medicine. Herein, the antibacterial and pharmacological properties of four fluoroquinolones: lomefloxacin, norfloxacin, ciprofloxacin, and ofloxacin have been studied. The objective of this study was to analyze the antibacterial characteristics of the different fluoroquinolones. Also, the pharmacological properties of the compounds including the Lipinski rule of five, absorption, distribution, metabolism, and excretion, LD50, drug likeliness, and toxicity were evaluated. We found that among all four FQ molecules, ofloxacin showed the highest antibacterial activity through in silico assays with a strong interaction (−38.52 kJ/mol) with the antibacterial target protein (topoisomerase-II DNA gyrase enzyme). The pharmacological and pharmacokinetic analysis also showed that the compounds ciprofloxacin, ofloxacin, lomefloxacin and norfloxacin have good pharmacological properties. Notably, ofloxacin was found to possess an IGC50 (concentration needed to inhibit 50% growth) value of 0.286 μg/L against the Tetrahymena pyriformis protozoa. It also tested negative for the Ames toxicity test, showing its non-carcinogenic character.
Absorption ; Anti-Bacterial Agents ; Bacterial Infections ; Ciprofloxacin ; Computer Simulation ; DNA Gyrase ; Fluoroquinolones* ; Humans ; Lethal Dose 50 ; Metabolism ; Norfloxacin ; Ofloxacin ; Tetrahymena pyriformis ; Toxicity Tests ; Veterinary Medicine

In order to clarify dynamic change of microbial community composition and to identify key functional bacteria in the cellulose degradation consortium, we studied several aspects of the biodegradation of filter papers and rice straws by the microbial consortium, the change of substrate degradation, microbial biomass and pH of fermentation broth. We extracted total DNA of the microbial consortium in different degradation stages for high-throughput sequencing of amplicons of bacterial 16 S rRNA genes. Based on the decomposition characteristics test, we defined the 12th, 72nd and 168th hours after inoculation as the initial stage, peak stage and end stage of degradation, respectively. The microbial consortium was mainly composed of 1 phylum, 2 classes, 2 orders, 7 families and 11 genera. With cellulose degradation, bacteria in the consortium showed different growth trends. The relative abundance of Brevibacillus and Caloramator decreased gradually. The relative abundance of Clostridium, Bacillus, Geobacillus and Cohnella increased gradually. The relative abundance of Ureibacillus, Tissierella, Epulopiscium was the highest in peak stage. The relative abundance of Paenibacillus and Ruminococcus did not change obviously in each stage. Above-mentioned 11 main genera all belonged to Firmicutes, which are thermophilic, broad pH adaptable and cellulose or hemicellulose degradable. During cellulose degradation by the microbial consortium, aerobic bacteria were dominant functional bacteria in the initial stage. However, the relative abundance of anaerobic bacteria increased gradually in middle and end stage, and replaced aerobic bacteria to become main bacteria to degrade cellulose.
Bacteria ; classification ; metabolism ; Biodegradation, Environmental ; Cellulose ; metabolism ; DNA, Bacterial ; genetics ; Microbial Consortia ; RNA, Ribosomal, 16S ; genetics

No abstract available.
Aged ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Cefotaxime/analogs & derivatives/therapeutic use ; Cholangiopancreatography, Endoscopic Retrograde ; Gallstones/surgery ; Gram-Negative Anaerobic Bacteria/drug effects/genetics/*isolation & purification ; Gram-Negative Bacterial Infections/*diagnosis/drug therapy/microbiology ; Humans ; Male ; Metronidazole/therapeutic use ; Microbial Sensitivity Tests ; RNA, Ribosomal, 16S/chemistry/genetics/metabolism ; Sequence Analysis, DNA ; Tomography, X-Ray Computed

No abstract available.
Anti-Bacterial Agents/*pharmacology ; Azabicyclo Compounds/*pharmacology ; Bacterial Proteins/genetics ; Ceftazidime/*pharmacology ; Cephalosporins/*pharmacology ; DNA, Bacterial/genetics/metabolism ; Drug Resistance, Bacterial/*drug effects ; Gram-Negative Bacteria/drug effects/*isolation & purification ; Humans ; Microbial Sensitivity Tests ; Penicillanic Acid/*analogs & derivatives/pharmacology ; Pseudomonas aeruginosa/drug effects/isolation & purification ; Real-Time Polymerase Chain Reaction

Bacterial Proteins ; chemistry ; genetics ; metabolism ; DNA, Bacterial ; chemistry ; genetics ; metabolism ; Gene Expression Regulation, Bacterial ; physiology ; Glutathione ; metabolism ; Listeria monocytogenes ; chemistry ; genetics ; metabolism ; Peptide Termination Factors ; chemistry ; genetics ; metabolism

BACKGROUND: We evaluated the performance of four commercial nucleic acid amplification tests (NAATs: Xpert C. difficile, BD MAX Cdiff, IMDx C. difficile for Abbott m2000, and Illumigene C. difficile) for direct and rapid detection of Clostridium difficile toxin genes. METHODS: We compared four NAATs on the same set of 339 stool specimens (303 prospective and 36 retrospective specimens) with toxigenic culture (TC). RESULTS: Concordance rate among four NAATs was 90.3% (306/339). Based on TC results, the sensitivity and specificity were 90.0% and 92.9% for Xpert; 86.3% and 89.3% for Max; 84.3% and 94.4% for IMDx; and 82.4% and 93.7% for Illumigene, respectively. For 306 concordant cases, there were 11 TC-negative/NAATs co-positive cases and 6 TC-positive/NAATs co-negative cases. Among 33 discordant cases, 18 were only single positive in each NAAT (Xpert, 1; Max, 12; IMDx, 1; Illumigene, 4). Positivity rates of the four NAATs were associated with those of semi-quantitative cultures, which were maximized in grade 3 (>100 colony-forming unit [CFU]) compared with grade 1 (<10 CFU). CONCLUSIONS: Commercial NAATs may be rapid and reliable methods for direct detection of tcdA and/or tcdB in stool specimens compared with TC. Some differences in the sensitivity of the NAATs may partly depend on the number of toxigenic C. difficile in stool specimens.
Bacterial Proteins/genetics ; Bacterial Toxins/genetics ; Clostridium Infections/*diagnosis/microbiology ; Clostridium difficile/*genetics/isolation & purification ; DNA, Bacterial/*analysis/metabolism ; Enterotoxins/genetics ; Feces/*microbiology ; Humans ; *Multiplex Polymerase Chain Reaction ; Reagent Kits, Diagnostic ; Sensitivity and Specificity

PURPOSE: In the gastric mucosa of Helicobacter pylori (H. pylori)-infected patients with gastritis or adenocarcinoma, proliferation of gastric epithelial cells is increased. Hyperproliferation is related to induction of oncogenes, such as β-catenin and c-myc. Even though transcription factors NF-κB and AP-1 are activated in H. pylori-infected cells, whether NF-κB or AP-1 regulates the expression of β-catenein or c-myc in H. pylori-infected cells has not been clarified. The present study was undertaken to investigate whether H. pylori-induced activation of NF-κB and AP-1 mediates the expression of oncogenes and hyperproliferation of gastric epithelial cells. MATERIALS AND METHODS: Gastric epithelial AGS cells were transiently transfected with mutant genes for IκBα (MAD3) and c-Jun (TAM67) or treated with a specific NF-κB inhibitor caffeic acid phenethyl ester (CAPE) or a selective AP-1 inhibitor SR-11302 to suppress activation of NF-κB or AP-1, respecively. As reference cells, the control vector pcDNA was transfected to the cells. Wild-type cells or transfected cells were cultured with or without H. pylori. RESULTS: H. pylori induced activation of NF-κB and AP-1, cell proliferation, and expression of oncogenes (β-catenein, c-myc) in AGS cells, which was inhibited by transfection of MAD3 and TAM67. Wild-type cells and the cells transfected with pcDNA showed similar activities of NF-κB and AP-1, proliferation, and oncogene expression regardless of treatment with H. pylori. Both CAPE and SR-11302 inhibited cell proliferation and expression of oncogenes in H. pylori-infected cells. CONCLUSION: H. pylori-induced activation of NF-κB and AP-1 regulates transcription of oncogenes and mediates hyperproliferation in gastric epithelial cells.
Blotting, Western ; Caffeic Acids ; Cell Line, Tumor ; Cell Proliferation ; DNA, Bacterial/analysis/genetics ; DNA-Binding Proteins/*metabolism ; Epithelial Cells/*metabolism ; Gastric Mucosa/*metabolism/pathology ; Gastritis/pathology ; Gene Expression Regulation, Bacterial ; Helicobacter Infections/metabolism/pathology/physiopathology ; Helicobacter pylori/pathogenicity/physiology ; Humans ; NF-kappa B/antagonists & inhibitors/*biosynthesis/metabolism ; Peptide Fragments ; Phenylethyl Alcohol/analogs & derivatives ; Proto-Oncogene Proteins c-jun ; Repressor Proteins ; Transcription Factor AP-1/*biosynthesis ; Transcription Factors/*metabolism ; beta Catenin/*metabolism

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) are important pathogens causing nosocomial infections in Korean hospitals. This study aimed to investigate the epidemiological and genetic diversity of clinical S. aureus isolates in healthcare settings from 2001 to 2008. METHODS: Samples and data were obtained from 986 individuals as part of the National Antimicrobial Surveillance Project, involving 10 regions nationwide. Molecular typing studies, including multilocus sequence typing (MLST) and staphylococcal cassette chromosome mec (SCCmec) typing were performed, and a representative clone of Korean MRSA was classified by combinational grouping using a DiversiLab (DL; bioMérieux, France) repetitive element polymerase chain reaction (rep-PCR) system. RESULTS: Nine Korean MRSA clones (KMRSA-1 to -9) were identified by analysis of genetic backgrounds and molecular characteristics. KMRSA-1 to -3, expressing clonal complex (CC) 5 (carrying SCCmec II), CC8 (carrying SCCmec III), and CC72 (carrying SCCmec IV) were spread nationwide. In contrast, KMRSA-6 was highly prevalent in Gyeongsangnam-do, and KMRSA-4 was highly prevalent in Jeollanam-do and Jeollabuk-do. CONCLUSIONS: Epidemic KMRSA clones were genetically similar to major clones identified from the USA, with the exception of KMRSA-2, which had the SCCmec III type. Our results provide important insights into the distribution and molecular genetics of MRSA strains in Korea and may aid in the monitoring of MRSA spread throughout the country.
Bacterial Proteins/genetics ; DNA, Bacterial/genetics/metabolism ; Electrophoresis, Gel, Pulsed-Field ; Hospitals ; Humans ; Methicillin-Resistant Staphylococcus aureus/*genetics/isolation & purification ; Multilocus Sequence Typing ; Multiplex Polymerase Chain Reaction ; Prevalence ; Republic of Korea/epidemiology ; Staphylococcal Infections/diagnosis/*epidemiology/microbiology