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Andres R Floto - One of the best experts on this subject based on the ideXlab platform.
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dissemination of Mycobacterium abscessus via global transmission networks
Nature microbiology, 2021Co-Authors: Jakko Van Ingen, Josephine M Bryant, Christopher Ruis, Scott C Bell, Rachel Thomson, Rebecca M Davidson, Nabeeh A Hasan, Michael J Strong, Andres R FlotoAbstract:Mycobacterium abscessus, a multidrug-resistant nontuberculous Mycobacterium, has emerged as a major pathogen affecting people with cystic fibrosis (CF). Although originally thought to be acquired independently from the environment, most individuals are infected with one of several dominant circulating clones (DCCs), indicating the presence of global transmission networks of M. abscessus. How and when these clones emerged and spread globally is unclear. Here, we use evolutionary analyses of isolates from individuals both with and without CF to reconstruct the population history, spatiotemporal spread and recent transmission networks of the DCCs. We demonstrate synchronous expansion of six unrelated DCCs in the 1960s, a period associated with major changes in CF care and survival. Each of these clones has spread globally as a result of rare intercontinental transmission events. We show that the DCCs, but not environmentally acquired isolates, exhibit a specific smoking-associated mutational signature and that current transmission networks include individuals both with and without CF. We therefore propose that the DCCs initially emerged in non-CF populations but were then amplified and spread through the CF community. While individuals with CF are probably the most permissive host, non-CF individuals continue to play a key role in transmission networks and may facilitate long-distance transmission.
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development of inhibitors against Mycobacterium abscessus trna m1g37 methyltransferase trmd using fragment based approaches
Journal of Medicinal Chemistry, 2019Co-Authors: Andrew J Whitehouse, S E Thomas, Karen P Brown, Alexander Fanourakis, Daniel S H Chan, Daben M J Libardo, Vitor Mendes, Helena I Boshoff, Andres R FlotoAbstract:Mycobacterium abscessus (Mab) is a rapidly growing species of multidrug-resistant nontuberculous mycobacteria that has emerged as a growing threat to individuals with cystic fibrosis and other pre-...
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Mycobacterium abscessus complex identification with matrix assisted laser desorption ionization time of flight mass spectrometry
Journal of Clinical Microbiology, 2015Co-Authors: Theofano Panagea, Andres R Floto, David H Pincus, Dorothy M Grogono, Melissa Jones, Josephine M Bryant, Julian Parkhill, Peter H GilliganAbstract:We determined that the Vitek MS Plus matrix-assisted laser desorption ionization–time of flight mass spectrometry using research-use-only (RUO) v.4.12 and in vitro-diagnostic (IVD) v.3.0 databases accurately identified 41 Mycobacterium abscessus subsp. abscessus and 13 M. abscessus subsp. massiliense isolates identified by whole-genome sequencing to the species but not the subspecies level, from Middlebrook 7H11 and Burkholderia cepacia selective agars. Peak analysis revealed three peaks potentially able to differentiate between subspecies.
Wonjung Koh - One of the best experts on this subject based on the ideXlab platform.
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rifabutin is active against Mycobacterium abscessus in mice
Antimicrobial Agents and Chemotherapy, 2020Co-Authors: Thomas Dick, Veronique Dartois, Wonjung Koh, Sung Jae Shin, Martin GengenbacherAbstract:There is no reliable cure for Mycobacterium abscessus lung disease. Rifampin is not used clinically due to poor in vitro potency. In contrast, we have shown that rifabutin, another approved rifamycin used to treat tuberculosis, is potent in vitro against M. abscessus Here, we report that rifabutin is as active as clarithromycin against M. abscessus K21 in NOD.CB17-Prkdcscid/NCrCrl mice. This suggests that rifabutin should be considered a repurposing candidate for patients with M. abscessus disease.
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Mycobacterium abscessus pulmonary disease individual patient data meta analysis
European Respiratory Journal, 2019Co-Authors: Nakwon Kwak, Wonjung Koh, Byung Woo Jhun, Charles L Daley, Margareth Pretti Dalcolmo, Geoffrey Eather, Regina Gayoso, Naoki Hasegawa, Ho Namkoong, Jimyung ParkAbstract:Treatment of Mycobacterium abscessus pulmonary disease (MAB-PD), caused by M. abscessus subsp. abscessus, M. abscessus subsp. massiliense or M. abscessus subsp. bolletii, is challenging.We conducted an individual patient data meta-analysis based on studies reporting treatment outcomes for MAB-PD to clarify treatment outcomes for MAB-PD and the impact of each drug on treatment outcomes. Treatment success was defined as culture conversion for ≥12 months while on treatment or sustained culture conversion without relapse until the end of treatment.Among 14 eligible studies, datasets from eight studies were provided and a total of 303 patients with MAB-PD were included in the analysis. The treatment success rate across all patients with MAB-PD was 45.6%. The specific treatment success rates were 33.0% for M. abscessus subsp. abscessus and 56.7% for M. abscessus subsp. massiliense For MAB-PD overall, the use of imipenem was associated with treatment success (adjusted odds ratio (aOR) 2.65, 95% CI 1.36-5.10). For patients with M. abscessus subsp. abscessus, the use of azithromycin (aOR 3.29, 95% CI 1.26-8.62), parenteral amikacin (aOR 1.44, 95% CI 1.05-1.99) or imipenem (aOR 7.96, 95% CI 1.52-41.6) was related to treatment success. For patients with M. abscessus subsp. massiliense, the choice among these drugs was not associated with treatment outcomes.Treatment outcomes for MAB-PD are unsatisfactory. The use of azithromycin, amikacin or imipenem was associated with better outcomes for patients with M. abscessus subsp. abscessus.
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mycobacteriological characteristics and treatment outcomes in extrapulmonary Mycobacterium abscessus complex infections
International Journal of Infectious Diseases, 2017Co-Authors: Suk Hyeon Jeong, Sung Jae Shin, Su Young Kim, Hee Jae Huh, Nam Yong Lee, Cheolin Kang, Doo Ryeon Chung, Kyong Ran Peck, Wonjung KohAbstract:Summary Objectives The differentiation between Mycobacterium abscessus subspecies abscessus ( M. abscessus ) and Mycobacterium abscessus subspecies massiliense ( M. massiliense ) and determination of the presence of inducible resistance to macrolide antibiotics are important factors in the management of patients with Mycobacterium abscessus complex (MABC) infections. Unlike pulmonary MABC infections, little information on extrapulmonary MABC infections is available. Methods The molecular identification of clinical isolates was performed, and the clinical characteristics and treatment outcomes of 20 consecutive patients with extrapulmonary MABC infections were assessed. Results M. abscessus and M. massiliense each caused 10 (50%) of the cases. Eight (80%) M. abscessus isolates that had inducible resistance to clarithromycin harbored an intact erm (41) gene of the T28 variant, whereas two (20%) M. abscessus isolates had the C28 erm (41) variant and were susceptible to clarithromycin. All M. massiliense isolates had a truncated erm (41) gene and were susceptible to clarithromycin. The drug susceptibility profiles other than clarithromycin were similar for the M. abscessus and M. massiliense isolates. Of the 20 patients, 17 (85%) showed a favorable outcome, including all patients with M. massiliense infection and 70% (7/10) of patients with M. abscessus infection. Favorable outcomes were associated with M. massiliense and M. abscessus isolates with a non-functional erm (41) gene ( p =0.049). Conclusions Precise species and subspecies identification and the determination of macrolide susceptibility are recommended for the optimal treatment of extrapulmonary MABC infections.
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mycobacterial characteristics and treatment outcomes in Mycobacterium abscessus lung disease
Clinical Infectious Diseases, 2017Co-Authors: Wonjung Koh, Su Young Kim, Byeongho Jeong, Kyeongman Jeon, Kyoung Un Park, Byung Woo Jhun, H K Lee, Hye Yun Park, Dae Hun Kim, Hee Jae HuhAbstract:Background Treatment outcomes of patients with Mycobacterium abscessus subspecies abscessus lung disease are poor, and the microbial characteristics associated with treatment outcomes have not been studied systematically. The purpose of this study was to identify associations between microbial characteristics and treatment outcomes in patients with M. abscessus lung disease. Methods Sixty-seven consecutive patients with M. abscessus lung disease undergoing antibiotic treatment for ≥12 months between January 2002 and December 2012 were included. Morphotypic and genetic analyses were performed on isolates from 44 patients. Results Final sputum conversion to culture negative occurred in 34 (51%) patients. Compared to isolates from 24 patients with persistently positive cultures, pretreatment isolates from 20 patients with final negative conversion were more likely to exhibit smooth colonies (9/20, 45% vs 2/24, 8%; P = .020), susceptibility to clarithromycin (7/20, 35% vs 1/24, 4%; P = .015), and be of the C28 sequevar with regard to the erm(41) gene (6/20, 30% vs 1/24, 4%; P = .035). Mycobacterium abscessus lung disease recurred in 5 (15%) patients after successful completion of antibiotic therapy. Genotypic analysis revealed that most episodes (22/24, 92%) of persistently positive cultures during antibiotic treatment and all cases of microbiologic recurrence after treatment completion were caused by different M. abscessus genotypes within a patient. Conclusions Precise identification to the subspecies level and analysis of mycobacterial characteristics could help predict treatment outcomes in patients with M. abscessus lung disease. Treatment failures and recurrences are frequently associated with multiple genotypes, suggesting reinfection. Clinical trials registration NCT00970801.
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advances in the management of pulmonary disease due to Mycobacterium abscessus complex
International Journal of Tuberculosis and Lung Disease, 2014Co-Authors: Wonjung Koh, Jason E Stout, Wing Wai YewAbstract:Mycobacterium abscessus complex is a group of rapidly growing mycobacteria, and an emerging cause of non-tuberculous mycobacterial lung disease in patients with cystic fibrosis and chronic lung diseases, such as bronchiectasis. M. abscessus complex is the most drug-resistant of the mycobacterial pathogens, resulting in limited therapeutic options and a high treatment failure rate. M. abscessus complex is comprised of three closely related subspecies: M. abscessus (sensu stricto), M. massiliense and M. bolletii. M. abscessus encodes a functional erythromycin ribosomal methylase gene, erm(41), which modifies the binding site for macrolide antibiotics, causing inducible macrolide resistance. However, this inducible macrolide resistance is not seen in M. massiliense, as the erm(41) gene of this subspecies is non-functional. Accordingly, treatment success rates with macrolide-based antibiotic treatment are much higher in patients with M. massiliense infections than in those infected with M. abscessus. Precise speciation of M. abscessus complex is important for predicting antibiotic susceptibilities and patient outcome.
Peter H Gilligan - One of the best experts on this subject based on the ideXlab platform.
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Mycobacterium abscessus complex identification with matrix assisted laser desorption ionization time of flight mass spectrometry
Journal of Clinical Microbiology, 2015Co-Authors: Theofano Panagea, Andres R Floto, David H Pincus, Dorothy M Grogono, Melissa Jones, Josephine M Bryant, Julian Parkhill, Peter H GilliganAbstract:We determined that the Vitek MS Plus matrix-assisted laser desorption ionization–time of flight mass spectrometry using research-use-only (RUO) v.4.12 and in vitro-diagnostic (IVD) v.3.0 databases accurately identified 41 Mycobacterium abscessus subsp. abscessus and 13 M. abscessus subsp. massiliense isolates identified by whole-genome sequencing to the species but not the subspecies level, from Middlebrook 7H11 and Burkholderia cepacia selective agars. Peak analysis revealed three peaks potentially able to differentiate between subspecies.
Dorothy M Grogono - One of the best experts on this subject based on the ideXlab platform.
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Mycobacterium abscessus complex identification with matrix assisted laser desorption ionization time of flight mass spectrometry
Journal of Clinical Microbiology, 2015Co-Authors: Theofano Panagea, Andres R Floto, David H Pincus, Dorothy M Grogono, Melissa Jones, Josephine M Bryant, Julian Parkhill, Peter H GilliganAbstract:We determined that the Vitek MS Plus matrix-assisted laser desorption ionization–time of flight mass spectrometry using research-use-only (RUO) v.4.12 and in vitro-diagnostic (IVD) v.3.0 databases accurately identified 41 Mycobacterium abscessus subsp. abscessus and 13 M. abscessus subsp. massiliense isolates identified by whole-genome sequencing to the species but not the subspecies level, from Middlebrook 7H11 and Burkholderia cepacia selective agars. Peak analysis revealed three peaks potentially able to differentiate between subspecies.
Sylvia Cardoso Leao - One of the best experts on this subject based on the ideXlab platform.
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emended description of Mycobacterium abscessus Mycobacterium abscessus subsp abscessus and Mycobacteriumabscessus subsp bolletii and designation of Mycobacteriumabscessus subsp massiliense comb nov
International Journal of Systematic and Evolutionary Microbiology, 2016Co-Authors: Enrico Tortoli, Sylvia Cardoso Leao, Maria Jesus Garcia, Thomas Kohl, Barbara A Brownelliott, Alberto Trovato, Sruthi Vasireddy, Christine Y Turenne, David E Griffith, Julie V PhilleyAbstract:The taxonomic position of members of the Mycobacterium abscessus complex has been the subject of intensive investigation and, in some aspects confusion, in recent years as a result of varying approaches to genetic data interpretation. Currently, the former species Mycobacterium massiliense and Mycobacterium bolletii are grouped together as Mycobacterium abscessus subsp. bolletii. They differ greatly, however, as the former M. bolletii has a functional erm(41) gene that confers inducible resistance to macrolides, the primary therapeutic antimicrobials for M. abscessus, while in the former M. massiliense the erm(41) gene is non-functional. Furthermore, previous whole genome studies of the M. abscessus group support the separation of M. bolletii and M. massiliense. To shed further light on the population structure of Mycobacterium abscessus, 43 strains and three genomes retrieved from GenBank were subjected to pairwise comparisons using three computational approaches: verage ucleotide dentity, enome to enome istance and single nucleotide polymorphism analysis. The three methods produced overlapping results, each demonstrating three clusters of strains corresponding to the same number of taxonomic entities. The distances were insufficient to warrant distinction at the species level, but met the criteria for differentiation at the subspecies level. Based on prior erm(41)-related phenotypic data and current genomic data, we conclude that the species M. abscessus encompasses, in adjunct to the presently recognized subspecies M. abscessus subsp. abscessus and M. abscessus subsp. bolletii, a third subspecies for which we suggest the name M. abscessus subsp. massiliense comb. nov. (type strain CCUG 48898T=CIP 108297T=DSM 45103T=KCTC 19086T).
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multilocus sequence analysis and rpob sequencing of Mycobacterium abscessus sensu lato strains
Journal of Clinical Microbiology, 2011Co-Authors: Edouard Macheras, Sylvia Cardoso Leao, Annelaure Roux, Valerie Sivadontardy, Cristina Gutierrez, Sylvaine Bastian, Moises Palaci, Elvira Richter, Sabine Ruschgerdes, Gaby E PfyfferAbstract:Mycobacterium abscessus, Mycobacterium bolletii, and Mycobacterium massiliense (Mycobacterium abscessus sensu lato) are closely related species that currently are identified by the sequencing of the rpoB gene. However, recent studies show that rpoB sequencing alone is insufficient to discriminate between these species, and some authors have questioned their current taxonomic classification. We studied here a large collection of M. abscessus (sensu lato) strains by partial rpoB sequencing (752 bp) and multilocus sequence analysis (MLSA). The final MLSA scheme developed was based on the partial sequences of eight housekeeping genes: argH, cya, glpK, gnd, murC, pgm, pta, and purH. The strains studied included the three type strains (M. abscessus CIP 104536(T), M. massiliense CIP 108297(T), and M. bolletii CIP 108541(T)) and 120 isolates recovered between 1997 and 2007 in France, Germany, Switzerland, and Brazil. The rpoB phylogenetic tree confirmed the existence of three main clusters, each comprising the type strain of one species. However, divergence values between the M. massiliense and M. bolletii clusters all were below 3% and between the M. abscessus and M. massiliense clusters were from 2.66 to 3.59%. The tree produced using the concatenated MLSA gene sequences (4,071 bp) also showed three main clusters, each comprising the type strain of one species. The M. abscessus cluster had a bootstrap value of 100% and was mostly compact. Bootstrap values for the M. massiliense and M. bolletii branches were much lower (71 and 61%, respectively), with the M. massiliense cluster having a fuzzy aspect. Mean (range) divergence values were 2.17% (1.13 to 2.58%) between the M. abscessus and M. massiliense clusters, 2.37% (1.5 to 2.85%) between the M. abscessus and M. bolletii clusters, and 2.28% (0.86 to 2.68%) between the M. massiliense and M. bolletii clusters. Adding the rpoB sequence to the MLSA-concatenated sequence (total sequence, 4,823 bp) had little effect on the clustering of strains. We found 10/120 (8.3%) isolates for which the concatenated MLSA gene sequence and rpoB sequence were discordant (e.g., M. massiliense MLSA sequence and M. abscessus rpoB sequence), suggesting the intergroup lateral transfers of rpoB. In conclusion, our study strongly supports the recent proposal that M. abscessus, M. massiliense, and M. bolletii should constitute a single species. Our findings also indicate that there has been a horizontal transfer of rpoB sequences between these subgroups, precluding the use of rpoB sequencing alone for the accurate identification of the two proposed M. abscessus subspecies.
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Proposal that Mycobacterium massiliense and Mycobacterium bolletii be united and reclassified as Mycobacterium abscessus subsp. bolletii comb. nov., designation of Mycobacterium abscessus subsp. abscessus subsp. nov. and emended description of Mycoba
International journal of systematic and evolutionary microbiology, 2010Co-Authors: Sylvia Cardoso Leao, Enrico Tortoli, Jean Paul Euzéby, Maria Jesus GarciaAbstract:The names 'Mycobacterium abscessus subsp. abscessus' and 'Mycobacterium abscessus subsp. massiliense', proposed by Leao et al. (2009, J Clin Microbiol 47, 2691-2698), cannot be validly published. The purpose of this report is to provide a description in accordance with the Rules of the Bacteriological Code (1990 Revision). Moreover, the proposal of the name 'Mycobacterium abscessus subsp. massiliense' is contrary to Rule 38 and the correct name of this taxon, at the rank of subspecies, is Mycobacterium abscessus subsp. bolletii comb. nov. A description of Mycobacterium abscessus subsp. abscessus subsp. nov. and an emended description of Mycobacterium abscessus are also given.
