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

2019 ◽  
Author(s):  
Nabeeh A. Hasan ◽  
Rebecca M. Davidson ◽  
L. Elaine Epperson ◽  
Sara M. Kammlade ◽  
Rachael R. Rodger ◽  
...  

AbstractNontuberculous 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 wereMycobacterium abscessus(59.5%), followed by species in theMycobacterium aviumcomplex (37.5%). Phylogenomic analyses of the threeM. abscessussubspecies revealed that more than half of CF patients had isolates in one of four dominant clones, including two dominant clones ofM. abscessussubspeciesabscessusand two dominant clones ofM. abscessussubspeciesmassiliense. M. aviumisolates 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 withM. abscessussubspecies, ten clusters of highly similar isolates from 26 patients were identified. Among the 26 patients in theM. abscessusclusters, 12 attended the same CF care centers. No highly similar isolate clusters were observed inM. 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.

Author(s):  
Rebecca M Davidson ◽  
Nabeeh A Hasan ◽  
L Elaine Epperson ◽  
Jeanne B Benoit ◽  
Sara M Kammlade ◽  
...  

2020 ◽  
pp. PHYTO-06-20-021
Author(s):  
Nicholas LeBlanc ◽  
Marc A. Cubeta ◽  
Jo Anne Crouch

Boxwood blight was first documented in Europe, prior to its recent colonization of North America, where it continues to have significant negative impacts on the ornamental industry. Due to near genetic uniformity in the two sister species of fungal plant pathogens that cause boxwood blight, understanding historical disease emergence and predicting future outbreaks is limited. The goal of this research was to apply population genomics to understand the role of pathogen diversification and migration in disease emergence. Specifically, we tested whether the primary pathogen species Calonectria pseudonaviculata has remained genetically isolated from its European-limited sister species C. henricotiae, while diversifying into clonal lineages that have migrated among continents. Whole-genome sequencing identified 1,608 single-nucleotide polymorphisms (SNPs) in 67 C. pseudonaviculata isolates from four continents and 1,017 SNPs in 13 C. henricotiae isolates from Europe. Interspecific genetic differentiation and an absence of shared polymorphisms indicated lack of gene flow between the sister species. Tests for intraspecific genetic structure in C. pseudonaviculata identified four genetic clusters, three of which corresponded to monophyletic phylogenetic clades. Comparison of evolutionary divergence scenarios among the four genetic clusters using approximate Bayesian computation indicated that the two C. pseudonaviculata genetic clusters currently found in the United States were derived from different sources, one from the first genetic cluster found in Europe and the second from an unidentified population. Evidence for multiple introductions of this pathogen into the United States and intercontinental migration indicates that future introductions are likely to occur and should be considered in plant disease quarantine regulation.


2019 ◽  
Vol 71 (1) ◽  
pp. 53-62 ◽  
Author(s):  
Gloria H Hong ◽  
Ana M Ortega-Villa ◽  
Sally Hunsberger ◽  
Ploenchan Chetchotisakd ◽  
Siriluck Anunnatsiri ◽  
...  

Abstract Background The natural history of anti-interferon-γ (IFN-γ) autoantibody-associated immunodeficiency syndrome is not well understood. Methods Data of 74 patients with anti-IFN-γ autoantibodies at Srinagarind Hospital, Thailand, were collected annually (median follow-up duration, 7.5 years). Annual data for 19 patients and initial data for 4 patients with anti-IFN-γ autoantibodies at the US National Institutes of Health were collected (median follow-up duration, 4.5 years). Anti-IFN-γ autoantibody levels were measured in plasma samples. Results Ninety-one percent of US patients were of Southeast Asian descent; there was a stronger female predominance (91%) in US than Thai (64%) patients. Mycobacterium abscessus (34%) and Mycobacterium avium complex (83%) were the most common nontuberculous mycobacteria in Thailand and the United States, respectively. Skin infections were more common in Thailand (P = .001), whereas bone (P < .0001), lung (P = .002), and central nervous system (P = .03) infections were more common in the United States. Twenty-four percent of Thai patients died, most from infections. None of the 19 US patients with follow-up data died. Anti-IFN-γ autoantibody levels decreased over time in Thailand (P < .001) and the United States (P = .017), with either cyclophosphamide (P = .01) or rituximab therapy (P = .001). Conclusions Patients with anti-IFN-γ autoantibodies in Thailand and the United States had distinct demographic and clinical features. While titers generally decreased with time, anti-IFN-γ autoantibody disease had a chronic clinical course with persistent infections and death. Close long-term surveillance for new infections is recommended.


2021 ◽  
Vol 9 (8) ◽  
pp. 1597
Author(s):  
Dominic Stephenson ◽  
Audrey Perry ◽  
Andrew Nelson ◽  
Ali E. Robb ◽  
Matthew F. Thomas ◽  
...  

Nontuberculous mycobacteria are important respiratory pathogens in patients with cystic fibrosis (CF). For diagnosis, international guidelines recommend culture of sputum that has been decontaminated via chemical treatment. Fifty-six sputum samples from 32 patients known to be previously colonized or infected with NTM were subdivided, and the aliquots were subjected to six different decontamination strategies, followed by quantitative culture for NTM. Thirty sputum samples contained Mycobacterium abscessus complex (MABSC) and 11 contained Mycobacterium avium complex (MAC). Decontamination strategies included treatment with N-acetyl L-cysteine with 2% sodium hydroxide (NALC-NaOH), 4% NaOH, 1% chlorhexidine, 0.5 N sulfuric acid, 5% oxalic acid, double decontamination with NALC-NaOH, followed by 5% oxalic acid, and saline (0.85%) as a control. The samples were also cultured directly with no treatment. Treatment with NALC-NaOH resulted in an average reduction in colony count of 87% for MABSC when compared with direct culture. NaOH at 4% caused a 98.3% average reduction in colony count. All treatments that included NaOH resulted in colony counts that were statistically lower than those obtained from direct culture or the saline-treated control (p < 0.05). Standard treatments using sulfuric or oxalic acids were less deleterious, but still resulted in an average reduction in colony count of at least 30%. The viability of MAC was much less affected by most decontamination treatments. In conclusion, the viability of MABSC was severely compromised by standard decontamination regimens. This supports recent evidence showing that optimal recovery of MABSC is achieved by culture on an appropriate selective agar without decontamination of sputum samples.


PEDIATRICS ◽  
1994 ◽  
Vol 94 (5) ◽  
pp. 741-742
Author(s):  
Sandeep K. Gupta ◽  
Ben Z. Katz

Mycobacterium tuberculosis (MTB) is a well described human pathogen.1 Less commonly, atypical or nontuberculous mycobacteria (NTM) can cause disease in humans. Recent studies report that NTM account for one-third of all pathogenic mycobacterial isolates in the United States.2 Mycobacterium avium-intracellulare complex (MAI) is the most common NTM causing human disease.2 It is also the most common mycobacterial cause of cervical lymphadenitis in children in areas with low endemic rates of MTB infection.3 MAI/NTM infection other than cervical adenitis is unusual in children, except in those that are immunosuppressed.4 Rarely, MAI presents as mediastinal or endobronchial disease in otherwise healthy children.


2018 ◽  
Vol 57 (2) ◽  
Author(s):  
Ravikiran Vasireddy ◽  
Sruthi Vasireddy ◽  
Barbara A. Brown-Elliott ◽  
Alexander L. Greninger ◽  
Rebecca M. Davidson ◽  
...  

ABSTRACTWe characterize three respiratory isolates of the recently described speciesMycobacterium talmoniaerecovered in Texas, Louisiana, and Massachusetts, including the first case of disease in a patient with underlying cystic fibrosis. The three isolates had a 100% match toM. talmoniaeNE-TNMC-100812Tby complete 16S rRNA,rpoBregion V, andhsp65 gene sequencing. Core genomic comparisons between one isolate and the type strain revealed an average nucleotide identity of 99.8%. The isolates were susceptible to clarithromycin, amikacin, and rifabutin, while resistance was observed for tetracyclines, ciprofloxacin, and linezolid.M. talmoniaeshould be added to the list of potential pulmonary pathogens, including in the setting of cystic fibrosis.


2018 ◽  
Vol 69 (3) ◽  
pp. 428-437 ◽  
Author(s):  
Eelco Franz ◽  
Ovidiu Rotariu ◽  
Bruno S Lopes ◽  
Marion MacRae ◽  
James L Bono ◽  
...  

AbstractBackgroundShiga toxin–producing Escherchia coli (STEC) O157:H7 is a zoonotic pathogen that causes numerous food and waterborne disease outbreaks. It is globally distributed, but its origin and the temporal sequence of its geographical spread are unknown.MethodsWe analyzed whole-genome sequencing data of 757 isolates from 4 continents, and performed a pan-genome analysis to identify the core genome and, from this, extracted single-nucleotide polymorphisms. A timed phylogeographic analysis was performed on a subset of the isolates to investigate its worldwide spread.ResultsThe common ancestor of this set of isolates occurred around 1890 (1845–1925) and originated from the Netherlands. Phylogeographic analysis identified 34 major transmission events. The earliest were predominantly intercontinental, moving from Europe to Australia around 1937 (1909–1958), to the United States in 1941 (1921–1962), to Canada in 1960 (1943–1979), and from Australia to New Zealand in 1966 (1943–1982). This pre-dates the first reported human case of E. coli O157:H7, which was in 1975 from the United States.ConclusionsInter- and intra-continental transmission events have resulted in the current international distribution of E. coli O157:H7, and it is likely that these events were facilitated by animal movements (eg, Holstein Friesian cattle). These findings will inform policy on action that is crucial to reduce the further spread of E. coli O157:H7 and other (emerging) STEC strains globally.


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