Correlation between rpoB gene mutation in Mycobacterium avium subspecies paratuberculosis and clinical rifabutin and rifampicin resistance for treatment of Crohn’s disease

Beckler, Daniel; Elwasila, Sammer; Ghobrial, George; Valentine, John F.; Naser, Saleh A.

doi:10.3748/wjg.14.2723

Cited by 14 publications

(8 citation statements)

References 45 publications

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“…SNPs in a specific 81-bp region of the rpoB gene are associated with Rifampicin (RIF) resistance in M. tuberculosis [ 106 ]. Beckler et al [ 107 ] determined that several MAP isolates that were resistant to RIF and to Rifabutin, also had mutations in the rpo B gene (compared with K10). In the current study, the complete rpo B gene sequence was found to be identical in JIII-386, Telford and K-10.…”

Section: Resultsmentioning

confidence: 99%

Complete Genome Sequence of Ovine Mycobacterium avium subsp. paratuberculosis Strain JIII-386 (MAP-S/type III) and Its Comparison to MAP-S/type I, MAP-C, and M. avium Complex Genomes

et al. 2020

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Mycobacterium avium (M. a.) subsp. paratuberculosis (MAP) is a worldwide-distributed obligate pathogen in ruminants causing Johne’s disease. Due to a lack of complete subtype III genome sequences, there is not yet conclusive information about genetic differences between strains of cattle (MAP-C, type II) and sheep (MAP-S) type, and especially between MAP-S subtypes I, and III. Here we present the complete, circular genome of MAP-S/type III strain JIII-386 (DE) closed by Nanopore-technology and its comparison with MAP-S/type I closed genome of strain Telford (AUS), MAP-S/type III draft genome of strain S397 (U.S.), twelve closed MAP-C strains, and eight closed M.-a.-complex-strains. Structural comparative alignments revealed clearly the mosaic nature of MAP, emphasized differences between the subtypes and the higher diversity of MAP-S genomes. The comparison of various genomic elements including transposases and genomic islands provide new insights in MAP genomics. MAP type specific phenotypic features may be attributed to genes of known large sequence polymorphisms (LSPSs) regions I–IV and deletions #1 and #2, confirmed here, but could also result from identified frameshifts or interruptions of various virulence-associated genes (e.g., mbtC in MAP-S). Comprehensive core and pan genome analysis uncovered unique genes (e.g., cytochromes) and genes probably acquired by horizontal gene transfer in different MAP-types and subtypes, but also emphasized the highly conserved and close relationship, and the complex evolution of M.-a.-strains.

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Section: Resultsmentioning

confidence: 99%

Complete Genome Sequence of Ovine Mycobacterium avium subsp. paratuberculosis Strain JIII-386 (MAP-S/type III) and Its Comparison to MAP-S/type I, MAP-C, and M. avium Complex Genomes

et al. 2020

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“…MAP, like other mycobacteria, has been shown to have the presence of resistant strains to Rifamycin compounds (including Rifampicin and Rifabutin), due to the presence of the rpoB gene. This will influence the response to AMAT [45][46][47].…”

Section: Patient Age Years Sex Prior Therapies Amat (Y/n) Amat Regimmentioning

confidence: 99%

Profound remission in Crohn’s disease requiring no further treatment for 3–23 years: a case series

et al. 2020

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Background: Crohn's disease (CD) is rising in incidence and has a high morbidity and increased mortality. Current treatment use immunosuppressives but efficacy is suboptimal, and relapse is common. It has been shown that there is an imbalance present in the gut microbiome (dysbiosis) in CD with a possible infective aetiology-Mycobacterium avium subsp. paratuberculosis (MAP) being the most proposed. Antibacterial therapy and Faecal Microbiota Transplantation (FMT) are emerging treatments which can result in clinical and endoscopic remission, if employed correctly. The objective of this study was to report on the treatment and clinical outcomes of patients with CD in prolonged remission.Results: Ten patients were identified to have achieved prolonged remission for 3-23 years (median 8.5 years). Of these, 7/10 took targeted Anti-MAP therapy (AMAT) for a median 36 months and then ceased AMAT treatment. After stopping AMAT five patients underwent Faecal Microbiota Transplantation (FMT) (average four infusions). In 4/7, AMAT was combined with infliximab (mean of six infusions) that was withdrawn within 6 months after fistulae resolution. One patient achieved deep mucosal healing with AMAT alone. Of the 3/10 patients not prescribed AMAT, one had a combination of anti-inflammatory agents and a single antibiotic (metronidazole) followed by FMT. The other two received only FMT for Clostridioides difficile Infection. Conclusions:Prolonged remission has been achieved for 3-23 years with individualised treatments, with the majority using AMAT ± infliximab and FMT. Treatment with antibiotics and/or FMT provides a potential new avenue for treatment of CD. These findings should stimulate thinking, investigations and better therapy against MAP and the dysbiosis of the gut flora, to enable higher rates of prolonged remission.

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“…Similar mutations in the rpoB genes of M. kansasii, M. leprae, the MAC, and M. ulcerans also confer rifamycin resistance (30,190,195,233,275), although a significant proportion of resistant MAC strains may lack a missense mutation in this gene (195). The most common mutations associated with clinically acquired resistance in M. tuberculosis cluster in an 80-bp region of the rpoB gene, with approximately 80% of isolates having a mutation in codon 526 or 531 (305,461).…”

Section: Inhibition Of Nucleic Acid Synthesismentioning

confidence: 99%

Antimicrobial Susceptibility Testing, Drug Resistance Mechanisms, and Therapy of Infections with Nontuberculous Mycobacteria

2012

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SUMMARY Within the past 10 years, treatment and diagnostic guidelines for nontuberculous mycobacteria have been recommended by the American Thoracic Society (ATS) and the Infectious Diseases Society of America (IDSA). Moreover, the Clinical and Laboratory Standards Institute (CLSI) has published and recently (in 2011) updated recommendations including suggested antimicrobial and susceptibility breakpoints. The CLSI has also recommended the broth microdilution method as the gold standard for laboratories performing antimicrobial susceptibility testing of nontuberculous mycobacteria. This article reviews the laboratory, diagnostic, and treatment guidelines together with established and probable drug resistance mechanisms of the nontuberculous mycobacteria.

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Correlation between rpoB gene mutation in Mycobacterium avium subspecies paratuberculosis and clinical rifabutin and rifampicin resistance for treatment of Crohn’s disease

Cited by 14 publications

References 45 publications

Complete Genome Sequence of Ovine Mycobacterium avium subsp. paratuberculosis Strain JIII-386 (MAP-S/type III) and Its Comparison to MAP-S/type I, MAP-C, and M. avium Complex Genomes

Complete Genome Sequence of Ovine Mycobacterium avium subsp. paratuberculosis Strain JIII-386 (MAP-S/type III) and Its Comparison to MAP-S/type I, MAP-C, and M. avium Complex Genomes

Profound remission in Crohn’s disease requiring no further treatment for 3–23 years: a case series

Antimicrobial Susceptibility Testing, Drug Resistance Mechanisms, and Therapy of Infections with Nontuberculous Mycobacteria

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