Population Structure and Local Adaptation of MAC Lung Disease Agent Mycobacterium avium subsp. hominissuis

Yano, Hirokazu; Iwamoto, Tomotada; Nishiuchi, Yukiko; Nakajima, Chie; Старкова, Д. А.; Mokrousov, Igor; Narvskaya, Olga; Yoshida, Shiomi; Arikawa, Kentaro; Nakanishi, Noriko; Osaki, Ken; Nakagawa, Ichirô; Ato, Manabu; Suzuki, Yasuhiko; Maruyama, Fumito

doi:10.1093/gbe/evx183

Cited by 47 publications

(74 citation statements)

References 83 publications

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“…In comparison to the population structure and highly similar clones of M. abscessus in US CF patients, M. avium, M. intracellulare and M. chimaera isolates were genetically diverse and largely unclustered. Additionally, US M. avium isolates were, by and large, distinct from clinical populations and lineages described previously in Asian studies 24,25 . US lineages of M. avium also grouped with reference isolates from non-CF patients, environmental samples from Europe 27,28 , and zoonotic isolates from Belgium 37 59 and lateral gene transfer of loci e.g.…”

Section: Discussionmentioning

confidence: 58%

“…No dominant clones of M. avium were observed. Of the previously described lineages of M. avium that included primarily Asian isolates 24,25 , only one US CF isolate was observed in the East Asian lineage (reference strain TH135 36 ). The highest proportion of CF-RDP M. avium isolates fell into lineage 3 (30/80 = 37%) followed by lineage 1 (16/80 = 20%), lineage 5 (14/80 = 17%), lineage 4 (12/80 = 15%), lineage 2 (7/80 = 8%), and the East-Asia lineage (1/80 = 1%).…”

Section: Mycobacterium Aviummentioning

confidence: 99%

“…To evaluate US M. avium isolates and lineages in a global context and among different hosts and reservoirs, we assessed their relationships to genomes from 15 clinical, 6 environmental, and 12 zoonotic isolates from Japan 24,25,36 , Germany [26][27][28] , Belgium 37 , Belarus (patient; unpublished), Canada (hen; unpublished) and France (pigeon; unpublished; Table S2). Lineage 1 included a respiratory isolate (IH-068) from a stable pulmonary patient in Japan 24 , a virulent isolate collected from a US HIV patient in 1983 (strain 104) 38 , one isolate from a US deer (unpublished), one isolate from a US bird (unpublished), two isolates collected from two German household dust samples 28 , four isolates from pigs in Belgium and Japan 25,37 and 16 CF-RDP isolates. Lineage 2 included a clinical isolate from Belarus (XTB13-223), a pulmonary isolate from Germany (MAH-P-9060-06), an isolate from a pig in Belgium 37 , and seven CF-RDP isolates.…”

Section: Mycobacterium Aviummentioning

confidence: 99%

“…Much of the current understanding of M. avium diversity in the US is based on genotyping methods such as variable nucleotide tandem repeats VNTR 18,19 and serotyping [20][21][22][23] , that lack the resolution of whole genome sequencing (WGS). Furthermore, genomic studies of M. avium are limited to non-CF isolate populations from Japan 24,25 and Germany [26][27][28] . US-based genomic studies of M. avium and other MAC species recovered from CF patients are needed to better understand modes of acquisition and the impact of genotype on clinical outcome.…”

Section: Introductionmentioning

confidence: 99%

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Population Genomics of Nontuberculous Mycobacteria Recovered from United States Cystic Fibrosis Patients

Epperson

et al. 2019

Preprint

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Nontuberculous mycobacteria (NTM) pose a threat to individuals with cystic fibrosis (CF) due to an increased prevalence of pulmonary infections, innate drug resistance of the bacteria, and potential transmission between CF patients. To explore the genetic diversity of NTM isolated from CF patients within the United States (US) and to identify potential transmission events, we sequenced and analyzed the genomes of 341 NTM isolates from 191 CF patients as part of a nationwide surveillance study. The most abundant species in the isolate cohort were Mycobacterium abscessus (59.5%), followed by species in the Mycobacterium avium complex (37.5%). Phylogenomic analyses of the three M. abscessus subspecies revealed that more than half of CF patients had isolates in one of four dominant clones, including two dominant clones of M. abscessus subspecies abscessus and two dominant clones of M. abscessus subspecies massiliense. M. avium isolates from US CF patients, however, do not have dominant clones and are phylogenetically diverse. Longitudinal NTM isolates were compared to determine genome-wide single nucleotide polymorphisms (SNPs) that occur within patients over time. This information was used to compare between and within-patient SNP distributions, to quantitatively define SNP thresholds suggestive of transmission, and calculate a posterior probability of recent transmission given the SNP distance between two isolates from different patients. Out of 114 patients with M. abscessus subspecies, ten clusters of highly similar isolates from 26 patients were identified. Among the 26 patients in the M. abscessus clusters, 12 attended the same CF care centers. No highly similar isolate clusters were observed in M. avium. Our study reveals the contrasting genomic diversity and epidemiology of two major NTM taxa and the potential for between-patient exposure and cross-transmission of these emerging pathogens.

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Section: Discussionmentioning

confidence: 58%

Section: Mycobacterium Aviummentioning

confidence: 99%

Section: Mycobacterium Aviummentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Population Genomics of Nontuberculous Mycobacteria Recovered from United States Cystic Fibrosis Patients

Epperson

et al. 2019

Preprint

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“…Following comparative genomic analysis was carried out as previously reported (50). In brief, the pan and core genomes were defined using Roary software (51).…”

Section: Methodsmentioning

confidence: 99%

Genome-wide assessment ofMycobacterium tuberculosisconditionally essential metabolic pathways

Minato

Gohl

Thiede

et al. 2019

Preprint

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Better understanding of essential cellular functions in pathogenic bacteria is important for the development of more effective antimicrobial agents. We performed a comprehensive identification of essential genes in Mycobacterium tuberculosis, the major causative agent of tuberculosis, using a combination of transposon insertion sequencing (Tn-seq) and comparative genomic analysis. To identify conditional essential genes by Tn-seq, we used media with different nutrient composition. Although many conditional gene essentialities were affected by the presence of relevant nutrient sources, we also found that the essentiality of genes in a subset of metabolic pathways was unaffected by metabolites. Comparative genomic analysis revealed that not all essential genes identified by Tn-seq were fully conserved within the M. tuberculosis complex including some existing anti-tubercular drug target genes. In addition, we utilized an available M. tuberculosis genome-scale metabolic model, iSM810, to predict M. tuberculosis gene essentiality in silico. Comparing the sets of essential genes experimentally identified by Tn-seq to those predicted in silico reveals the capabilities and limitations of gene essentiality predictions highlighting the complexity of M. tuberculosis essential metabolic functions. This study provides a promising platform to study essential cellular functions in M. tuberculosis.Author SummaryMycobacterium tuberculosis causes 10 million cases of tuberculosis (TB) each year resulting in over one million deaths. TB therapy is challenging because it requires a minimum of six months of treatment with multiple drugs. Protracted treatment times and the emergent spread of drug resistant TB necessitate the identification of novel targets for drug discovery to curb this global health threat. Essential functions, defined as those indispensable for growth and/or survival, are potential targets for new antimicrobial drugs. In this study, we aimed to define gene essentialities of M. tuberculosis on a genome-wide scale to comprehensively identify potential targets for drug discovery. We utilized a combination of experimental (functional genomics) and in silico approaches (comparative genomics and flux balance analysis). Our functional genomics approach identified sets of genes whose essentiality was affected by nutrient availability. Comparative genomics revealed that not all essential genes were fully conserved within the M. tuberculosis complex. Comparing sets of essential genes identified by functional genomics to those predicted by flux balance analysis highlighted gaps in current knowledge regarding M. tuberculosis metabolic capabilities. Thus, our study identifies numerous potential anti-tubercular drug targets and provides a comprehensive picture of the complexity of M. tuberculosis essential cellular functions.

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A survey of clarithromycin monotherapy and long‐term administration of ethambutol for patients with MAC lung disease in Japan: A retrospective cohort study using the database of health insurance claims

Iwao

Kato

Ito

et al. 2019

Pharmacoepidemiology and Drug

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Background: The number of patients with nontuberculous mycobacteriosis (NTM) has increased exponentially in recent years. In Japan, approximately 88.8% of patients with NTM suffer from Mycobacterium avium-intracellulare complex (MAC) lung disease. Incidence of MAC lung disease is increasing in particularly among the middle-aged and elderly women owing to a rapid increase in nontuberculous mycobacterial infections.General treatment for MAC lung disease is chemotherapy. The type of chemotherapy recommended by specialists to prevent the development of a drug-resistant strain of the bacteria consists of a combination of clarithromycin (CAM), rifampicin, and ethambutol (EB). CAM monotherapy is contraindicated by specialists owing to its high potential to induce drug-resistant bacterial strains in patients with MAC lung disease.In addition, administering EB at doses not less than 1000 mg d −1 is not recommended to avoid adverse drug reactions. However, it is unclear how much such treatment cases exist in real world clinical settings. This is because no long-term investigation has been carried out. Materials and Methods:This study investigated treatment with these drugs from 2005 to 2017, by studying 1135 patients with MAC lung disease based on health insurance claims database.Results: Results showed that approximately 9.2% (101 cases) were prescribed longterm CAM monotherapy for 3 months or longer and approximately 3.6% (18 cases) were prescribed high doses of EB. Conclusion: CAM monotherapy over a long period of time is potentially detrimental to some patients. Better awareness of the types of treatments and their potential negative effects will be beneficial to clinical practitioners. K E Y W O R D S clarithromycin monotherapy, ethambutol, insurance claims database, Mycobacterium avium-intracellulare complex, nontuberculous mycobacteriosis, pharmacoepidemiology

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Population Structure and Local Adaptation of MAC Lung Disease Agent Mycobacterium avium subsp. hominissuis

Cited by 47 publications

References 83 publications

Population Genomics of Nontuberculous Mycobacteria Recovered from United States Cystic Fibrosis Patients

Population Genomics of Nontuberculous Mycobacteria Recovered from United States Cystic Fibrosis Patients

Genome-wide assessment ofMycobacterium tuberculosisconditionally essential metabolic pathways

A survey of clarithromycin monotherapy and long‐term administration of ethambutol for patients with MAC lung disease in Japan: A retrospective cohort study using the database of health insurance claims

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