Rifabutin and rifampin resistance levels and associated rpoB mutations in clinical isolates of Mycobacterium tuberculosis complex

Berrada, Zenda L.; Lin, Shou-Yean Grace; Rodwell, Timothy C.; Nguyen, Duylinh; Schecter, Gisela; Pham, Lucy; Janda, J. Michael; ElMaraachli, Wael; Catanzaro, Antonino; Desmond, Edward

doi:10.1016/j.diagmicrobio.2016.01.019

Cited by 61 publications

(56 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Some of these drawbacks could be overcome by designing the assay to specifically address the detection of synonymous mutations as recently done for the Xpert Ultra; however, this strategy requires a priori knowledge of all the possible silent mutations in the targeted region. Fourth, clear understanding of the relationship between genotype and phenotype and clinical outcome is not always available, and several factors contribute in complicating the clinical interpretation of genetic polymorphisms …”

Section: Discussionmentioning

confidence: 99%

“…Fourth, clear understanding of the relationship between genotype and phenotype and clinical outcome is not always available, and several factors contribute in complicating the clinical interpretation of genetic polymorphisms. 19,78,79,[182][183][184][185][186][187][188][189] Beside determination of drug resistance patterns, the era of personalized medicine advocates for improved interpretation of genotype for clinical management. Increasing evidence supports that different groups of bacteria (lineages) have different features in terms of host-pathogen interactions and/or transmission (reviewed in Ref.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Drug resistance mechanisms and drug susceptibility testing for tuberculosis

et al. 2018

View full text Add to dashboard Cite

Tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB) is the deadliest infectious disease and the associated global threat has worsened with the emergence of drug resistance, in particular multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB). Although the World Health Organization (WHO) End-TB Strategy advocates for universal access to antimicrobial susceptibility testing, this is not widely available and/or it is still underused. The majority of drug resistance in clinical MTB strains is attributed to chromosomal mutations. Resistance-related mutations could also exert certain fitness cost to the drug-resistant MTB strains and growth fitness could be restored by the presence of compensatory mutations. Understanding these underlying mechanisms could provide an important insight into TB pathogenesis and predict the future trend of MDR-TB global pandemic. This review covers the mechanisms of resistance in MTB and provides a comprehensive overview of current phenotypic and molecular approaches for drug susceptibility testing, with particular attention to the methods endorsed and recommended by the WHO.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Drug resistance mechanisms and drug susceptibility testing for tuberculosis

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Although high-level cross-resistance between the two rifamycins is reported, some studies have shown RFB susceptibility in RIF-resistant strains of M. tuberculosis in association with specific rpoB mutations (Cavusoglu et al, 2004; Yoshida et al, 2010; Jamieson et al, 2014; ElMaraachli et al, 2015). Thus, it has been argued that knowing the type of rpoB mutation may have clinical implications for guiding rifamycin-based therapeutic regimens (Sirgel et al, 2013; Berrada et al, 2016). …”

Section: Introductionmentioning

confidence: 99%

Correlation of rpoB Mutations with Minimal Inhibitory Concentration of Rifampin and Rifabutin in Mycobacterium tuberculosis in an HIV/AIDS Endemic Setting, South Africa

Rukasha

Said

Omar³

et al. 2016

Front. Microbiol.

View full text Add to dashboard Cite

Treatment of tuberculosis (TB) and HIV co-infections is often complicated by drug-to-drug interactions between anti-mycobacterial and anti-retroviral agents. Rifabutin (RFB) is an alternative to rifampin (RIF) for TB regimens and is recommended for HIV patients concurrently receiving protease inhibitors because of reduced induction of CYP3A4. This study sought to determine the proportion of RFB susceptible isolates among RIF-resistant strains in a high HIV prevalence setting in South Africa. In addition, the study explored the association between rpoB mutations and minimum inhibitory concentrations (MIC) of RIF and RFB. A total of 189 multidrug resistant (MDR) Mycobacterium tuberculosis isolates from the Centre for Tuberculosis repository were analyzed. The MICs were determined using a MYCOTB Sensititre plate method and the rpoB gene was sequenced. Of the 189 MDR isolates, 138 (73%) showed resistance to both RIF and RFB, while 51 (27%) isolates were resistant to RIF but retained susceptibility to RFB. The S531L was the most frequent rpoB point mutation in 105/189 (56%) isolates, followed by H526Y in 27/189 (14%) isolates. Resistance to both RIF and RFB was found predominantly in association with mutations S531L (91/105, 87%), H526Y (20/27, 74%), and H526D (15/19, 79%), while D516V (15/17, 88%), and L533P (3/4, 75%) were found in RIF-resistant, RFB-susceptible isolates. This study has shown that up to 27% of MDR-TB patients in South Africa may benefit from a treatment regimen that includes RFB.

show abstract

“…At times, variants with lower MICs are preferentially selected at lower rifampicin concentrations in the laboratory and clinic (van Ingen et al, 2011;Lindsey et al, 2013;Berrada et al, 2016). Mutations with high rifampicin resistance confer growth defect because they occur close to the catalytic site of RNA polymerase (Campbell et al, 2001) and consequently are detrimental to the cell (Brandis & Hughes, 2018).…”

Section: Fitness Estimates Help Understand the Biochemical Basis For mentioning

confidence: 99%

CRISPR /Cas9 recombineering‐mediated deep mutational scanning of essential genes in Escherichia coli

Choudhury

Fenster

Fankhauser

et al. 2020

Molecular Systems Biology

View full text Add to dashboard Cite

Deep mutational scanning can provide significant insights into the function of essential genes in bacteria. Here, we developed a high‐throughput method for mutating essential genes of Escherichia coli in their native genetic context. We used Cas9‐mediated recombineering to introduce a library of mutations, created by error‐prone PCR, within a gene fragment on the genome using a single gRNA pre‐validated for high efficiency. Tracking mutation frequency through deep sequencing revealed biases in the position and the number of the introduced mutations. We overcame these biases by increasing the homology arm length and blocking mismatch repair to achieve a mutation efficiency of 85% for non‐essential genes and 55% for essential genes. These experiments also improved our understanding of poorly characterized recombineering process using dsDNA donors with single nucleotide changes. Finally, we applied our technology to target rpoB, the beta subunit of RNA polymerase, to study resistance against rifampicin. In a single experiment, we validate multiple biochemical and clinical observations made in the previous decades and provide insights into resistance compensation with the study of double mutants.

show abstract

Rifabutin and rifampin resistance levels and associated rpoB mutations in clinical isolates of Mycobacterium tuberculosis complex

Cited by 61 publications

References 36 publications

Drug resistance mechanisms and drug susceptibility testing for tuberculosis

Drug resistance mechanisms and drug susceptibility testing for tuberculosis

Correlation of rpoB Mutations with Minimal Inhibitory Concentration of Rifampin and Rifabutin in Mycobacterium tuberculosis in an HIV/AIDS Endemic Setting, South Africa

CRISPR /Cas9 recombineering‐mediated deep mutational scanning of essential genes in Escherichia coli

Contact Info

Product

Resources

About