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rpoB mutation

Camilo Beltrán-Alzate, Fernando López Díaz, Marcela Romero-Montoya, Rama Sakamuri, Wei Li, Miyako Kimura, Patrick Brennan, Nora Cardona-Castro
An active search for Mycobacterium leprae drug resistance was carried out, 243 multibacillary patients from endemic regions of Colombia were included from 2004 to 2013 in a surveillance program. This program was a World Health Organization initiative for drug resistance surveillance in leprosy, where Colombia is a sentinel country. M. leprae DNA from slit skin smear and/or skin biopsy samples was amplified and sequenced to identify mutations in the drug resistance determining region (DRDR) in rpoB, folP1, gyrA, and gyrB, the genes responsible for rifampicin, dapsone and ofloxacin drug-resistance, respectively...
October 2016: PLoS Neglected Tropical Diseases
Neha S Shah, S Y Grace Lin, Pennan M Barry, Yi-Ning Cheng, Gisela Schecter, Ed Desmond
Background.  Data from international settings suggest that isolates of Mycobacterium tuberculosis with rpoB mutations testing phenotypically susceptible to rifampin (RIF) may have clinical significance. We analyzed treatment outcomes of California patients with discordant molecular-phenotypic RIF results. Methods.  We included tuberculosis (TB) patients, during 2003-2013, whose specimens tested RIF susceptible phenotypically but had a rpoB mutation determined by pyrosequencing. Demographic data were abstracted from the California TB registry...
September 2016: Open Forum Infectious Diseases
Nicola Casali, Agnieszka Broda, Simon R Harris, Julian Parkhill, Timothy Brown, Francis Drobniewski
BACKGROUND: A large isoniazid-resistant tuberculosis outbreak centred on London, United Kingdom, has been ongoing since 1995. The aim of this study was to investigate the power and value of whole genome sequencing (WGS) to resolve the transmission network compared to current molecular strain typing approaches, including analysis of intra-host diversity within a specimen, across body sites, and over time, with identification of genetic factors underlying the epidemiological success of this cluster...
October 2016: PLoS Medicine
Cláudia Gomes, Sandra Martínez-Puchol, Lidia Ruiz-Roldán, Maria J Pons, Juana Del Valle Mendoza, Joaquim Ruiz
The objective was to develop and characterise in vitro Bartonella bacilliformis antibiotic resistant mutants. Three B. bacilliformis strains were plated 35 or 40 times with azithromycin, chloramphenicol, ciprofloxacin or rifampicin discs. Resistance-stability was assessed performing 5 serial passages without antibiotic pressure. MICs were determined with/without Phe-Arg-β-Napthylamide and artesunate. Target alterations were screened in the 23S rRNA, rplD, rplV, gyrA, gyrB, parC, parE and rpoB genes. Chloramphenicol and ciprofloxacin resistance were the most difficult and easiest (>37...
September 26, 2016: Scientific Reports
Emmanuel Andre, Léonie Goeminne, Andrea M Cabibbe, Patrick Beckert, Benoît Kabamba Mukadi, Vanessa Mathys, Sébastien Gagneux, Stefan Niemann, Jakko Van Ingen, Emmanuelle Cambau
The rpoB gene codes for the RNA polymerase β subunit, which is the target of rifampicin, an essential drug in the treatment of tuberculosis and other mycobacterial infections. This gene is present in all bacteria, but its length and nucleotide sequence vary between bacterial species, including mycobacteria Mutations in the rpoB gene alter the structure of this protein and cause drug resistance. To describe the resistance-associated mutations, the scientific and medical communities have been using since 1993, a numbering system based on the Escherichia coli sequence annotation...
September 21, 2016: Clinical Microbiology and Infection
Didi Bang, Siri Rytcher Andersen, Edita Vasiliauskienė, Erik Michael Rasmussen
The emergence of extensively drug-resistant tuberculosis (XDR-TB) hampers infection control. To assess the performance of an extended rapid novel molecular analysis for the detection of resistance conferring mutations to fluoroquinolones (gyrA, gyrB genes) and aminoglycosides/cyclic peptides (16S rRNA rrs gene, eis promotor region) compared to phenotypic susceptibility and sequencing, 43 multidrug-resistant (MDR) and 10 susceptible clinical isolates were analyzed. Results were compared to a previous version...
August 31, 2016: Diagnostic Microbiology and Infectious Disease
Dulce Maria Juarez-Eusebio, Daniela Munro-Rojas, Raquel Muñiz-Salazar, Rafael Laniado-Laborín, Jose Armando Martinez-Guarneros, Carlos A Flores-López, Roberto Zenteno-Cuevas
Mexico is one of the most important contributors of multidrug resistance tuberculosis (MDR-TB) in Latin-America, however little is known about the molecular characteristics of these strains. For this reason, the objective of this work was to determine the genotype and characterize polymorphisms in genes associated with resistance to rifampicin, isoniazid, and second-line drugs in isolates from two regions of Mexico with high prevalence of drug resistant tuberculosis. Clinical isolates from individuals with confirmed MDR-TB were genotyped using MIRU-VNTR 12 loci...
September 13, 2016: Infection, Genetics and Evolution
Franziska Pietsch, Jessica M Bergman, Gerrit Brandis, Linda L Marcusson, Anna Zorzet, Douglas L Huseby, Diarmaid Hughes
OBJECTIVES: Resistance to the fluoroquinolone drug ciprofloxacin is commonly linked to mutations that alter the drug target or increase drug efflux via the major AcrAB-TolC transporter. Very little is known about other mutations that might also reduce susceptibility to ciprofloxacin. We discovered that an Escherichia coli strain experimentally evolved for resistance to ciprofloxacin had acquired a mutation in rpoB, the gene coding for the β-subunit of RNA polymerase. The aim of this work was to determine whether this mutation, and other mutations in rpoB, contribute to ciprofloxacin resistance and, if so, by which mechanism...
September 12, 2016: Journal of Antimicrobial Chemotherapy
Sophia B Georghiou, Marva Seifert, Shou-Yean Lin, Donald Catanzaro, Richard S Garfein, Roberta L Jackson, Valeriu Crudu, Camilla Rodrigues, Thomas C Victor, Antonino Catanzaro, Timothy C Rodwell
BACKGROUND: Rapid molecular diagnostics, with their ability to quickly identify genetic mutations associated with drug resistance in Mycobacterium tuberculosis clinical specimens, have great potential as tools to control multi- and extensively drug-resistant tuberculosis (M/XDR-TB). The Qiagen PyroMark Q96 ID system is a commercially available pyrosequencing (PSQ) platform that has been validated for rapid M/XDR-TB diagnosis. However, the details of the assay's diagnostic and technical performance have yet to be thoroughly investigated in diverse clinical environments...
2016: BMC Infectious Diseases
Leonie Greipel, Sebastian Fischer, Jens Klockgether, Marie Dorda, Samira Mielke, Lutz Wiehlmann, Nina Cramer, Burkhard Tümmler
The chronic airway infections with Pseudomonas aeruginosa in people with cystic fibrosis (CF) are treated with aerosolized antibiotics, oral fluoroquinolones and/or intravenous combination therapy with aminoglycosides and β-lactam antibiotics. An international strain collection of 361 P. aeruginosa isolates from 258 CF patients seen at 30 CF clinics was examined for mutations in 17 antimicrobial susceptibility and resistance loci that had been identified as hot spots of mutation by genome sequencing of serial isolates from a single CF clinic...
August 29, 2016: Antimicrobial Agents and Chemotherapy
Benjamin J Metcalf, Sopio Chochua, Robert E Gertz, Zhongya Li, Hollis Walker, Theresa Tran, Paulina A Hawkins, Anita Glennen, Ruth Lynfield, Yuan Li, Lesley McGee, Bernard Beall
OBJECTIVES: We assessed our whole genome sequence (WGS) pipeline for accurate prediction of current antimicrobial phenotypes. METHODS: For 2316 invasive pneumococcal isolates (IPD) recovered during 2015 we compared WGS pipeline data to broth dilution testing (BDT) for 18 antimicrobials. RESULTS: For 11 antimicrobials categorical discrepancies were assigned when WGS-predicted minimum inhibitory concentrations (MICs) and BDT MICs resulted in different predictions for susceptibility, intermediate-resistance or resistance, ranging from 0...
August 16, 2016: Clinical Microbiology and Infection
Nurul-Ain Ismail, Mohd Fazli Ismail, Siti Suraiya Md Noor, Siti Nazrina Camalxaman
BACKGROUND: Drug resistant tuberculosis (DR-TB) remains a public health issue that is of major concern on a global scale. The characterisation of clinical isolates may provide key information regarding the underlying mechanisms of drug resistance, and helps to augment therapeutic options. This study aims to evaluate the frequency of gene mutations associated with Rifampicin (RIF) and Isoniazid (INH) resistance among nine clinical isolates. METHODS: A total of nine drug resistant Mycobacterium tuberculosis clinical isolates were screened for genetic mutations in rpoB and katusing polymerase chain reaction (PCR) amplification and DNA sequencing...
January 2016: Malaysian Journal of Medical Sciences: MJMS
Irfan Ullah, Aamer Ali Shah, Anila Basit, Mazhar Ali, Afsar Khan, Ubaid Ullah, Muhammad Ihtesham, Sumaira Mehreen, Anita Mughal, Arshad Javaid
BACKGROUND: Multi-drug resistant tuberculosis (MDR-TB) is a major public health problem especially in developing countries. World Health Organization (WHO) recommends use of Xpert MTB/RIF assay to simultaneously detecting Mycobacterium tuberculosis (MTB) and rifampicin (RIF) resistance. The primary objective of this study was to determine the frequency of MDR-TB in patients suspected to have drug resistance in Khyber Pakhtunkhwa. The frequency of probes for various rpoB gene mutations using Xpert MTB/RIF assay within 81 bp RRDR (Rifampicin Resistance Determining Region) was the secondary objective...
2016: BMC Infectious Diseases
Joanna Spinato, Élyse Boivin, Émilie Bélanger-Trudelle, Huguette Fauchon, Cécile Tremblay, Hafid Soualhine
BACKGROUND: The increasing emergence of drug-resistant tuberculosis presents a threat to the effective control of tuberculosis (TB). Rapid detection of drug-resistance is more important than ever to address this scourge. The purpose of this study was to genotypically characterize the first-line antitubercular drug-resistant isolates collected over 11 years in Quebec. RESULTS: The main mutations found in our resistant strains collection (n = 225) include: the S315T substitution in katG (50...
2016: BMC Microbiology
Jocelyn Ang, Lisa Yun Song, Sara D'Souza, Irene L Hong, Rohan Luhar, Madeline Yung, Jeffrey H Miller
UNLABELLED: We tested pairwise combinations of classical base analog mutagens in Escherichia coli to study possible mutagen synergies. We examined the cytidine analogs zebularine (ZEB) and 5-azacytidine (5AZ), the adenine analog 2-aminopurine (2AP), and the uridine/thymidine analog 5-bromodeoxyuridine (5BrdU). We detected a striking synergy with the 2AP plus ZEB combination, resulting in hypermutability, a 35-fold increase in mutation frequency (to 53,000 × 10(-8)) in the rpoB gene over that with either mutagen alone...
October 15, 2016: Journal of Bacteriology
I D Otchere, A Asante-Poku, S Osei-Wusu, A Baddoo, E Sarpong, A H Ganiyu, S Y Aboagye, A Forson, F Bonsu, A I Yahayah, K Koram, S Gagneux, D Yeboah-Manu
We spoligotyped and screened 1490 clinical Mycobacterium tuberculosis complex strains from Northern and Greater Accra regions of Ghana against INH and RIF using the microplate alamar blue phenotypic assay. Specific drug resistance associated genetic elements of drug resistant strains were analyzed for mutations. A total of 111 (7.5%), 10 (0.7%) and 40 (2.6%) were mono-resistant to INH, RIF, and MDR, respectively. We found the Ghana spoligotype to be associated with drug resistance (INH: 22.1%; p = 0.0000, RIF: 6...
July 2016: Tuberculosis
Patricia Fajardo-Cavazos, Wayne L Nicholson
Bacteria of the genus Staphylococcus are persistent inhabitants of human spaceflight habitats and represent potential opportunistic pathogens. The effect of the human spaceflight environment on the growth and the frequency of mutations to antibiotic resistance in the model organism Staphylococcus epidermidis strain ATCC12228 was investigated. Six cultures of the test organism were cultivated in biological research in canisters-Petri dish fixation units for 122 h on orbit in the International Space Station (ISS) as part of the SpaceX-3 resupply mission...
2016: Frontiers in Microbiology
Richa Kumari, Rajneesh Tripathi, Alok Prakash Pandey, Tuhina Banerjee, Pallavi Sinha, Shampa Anupurba
BACKGROUND: Drug resistance in tuberculosis is a major public health challenge in developing countries. The limited data available on drug resistance in extra pulmonary tuberculosis stimulated us to design our study on anti-tuberculosis drug resistance pattern in cases of extra pulmonary tuberculosis in a tertiary referral hospital of North India. We performed Geno Type MTBDRplus assay in comparison with conventional drug susceptibility testing by proportion method to study the mutation patterns in rpoB, katG and inhA genes...
2016: PloS One
Fedora Lanzas, Thomas R Ioerger, Harita Shah, William Acosta, Petros C Karakousis
The turnaround times for conventional methods used to detect Mycobacterium tuberculosis in sputum samples and to obtain drug susceptibility information are long in many developing countries, including Panama, leading to delays in appropriate treatment initiation and continued transmission in the community. We evaluated the performance of a molecular line probe assay, the Genotype MTBDRplus version 2.0 assay, in detecting M. tuberculosis complex directly in respiratory specimens from smear-positive tuberculosis cases from four different regions in Panama, as well as the most frequent mutations in genes conferring resistance to isoniazid (katG and inhA) and rifampin (rpoB)...
October 2016: Journal of Clinical Microbiology
Maite Villanueva, Ambre Jousselin, Kristoffer T Baek, Julien Prados, Diego O Andrey, Adriana Renzoni, Hanne Ingmer, Dorte Frees, William L Kelley
UNLABELLED: Staphylococcus aureus is capable of causing a remarkable spectrum of disease, ranging from mild skin eruptions to life-threatening infections. The survival and pathogenic potential of S. aureus depend partly on its ability to sense and respond to changes in its environment. Spx is a thiol/oxidative stress sensor that interacts with the C-terminal domain of the RNA polymerase RpoA subunit, leading to changes in gene expression that help sustain viability under various conditions...
October 1, 2016: Journal of Bacteriology
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