Whole-genome sequencing (WGS) has recently been used to investigate acquisition of Mycobacterium ... more Whole-genome sequencing (WGS) has recently been used to investigate acquisition of Mycobacterium abscessus . Investigators have reached conflicting conclusions about the meaning of genetic distances for interpretation of person-to-person transmission.
International journal of systematic and evolutionary microbiology, Jan 15, 2017
A novel slowly growing, non-chromogenic species of the class Actinobacteria was isolated from a h... more A novel slowly growing, non-chromogenic species of the class Actinobacteria was isolated from a human respiratory sample in Nebraska, USA, in 2012. Analysis of the internal transcribed spacer sequence supported placement into the genus Mycobacterium with high sequence similarity to a previously undescribed strain isolated from a patient respiratory sample from Oregon, USA, held in a collection in Colorado, USA, in 2000. The two isolates were subjected to phenotypic testing and whole genome sequencing and found to be indistinguishable. The bacteria were acid-fast stain-positive, rod-shaped and exhibited growth after 7-10 days on solid media at temperatures ranging from 25 to 42°C. Colonies were non-pigmented, rough and slightly raised. Analyses of matrix-assisted laser desorption ionization time-of-flight profiles showed no matches against a reference library of 130 mycobacterial species. Full-length 16S rRNA gene sequences were identical for the two isolates, the average nucleotide ...
Lung disease caused by nontuberculous mycobacteria (NTM) is an emerging infectious disease of glo... more Lung disease caused by nontuberculous mycobacteria (NTM) is an emerging infectious disease of global significance. Epidemiologic studies have shown the Hawaiian Islands have the highest prevalence of NTM lung infections in the United States. However, potential environmental reservoirs and species diversity have not been characterized. In this cross-sectional study, we describe molecular and phylogenetic comparisons of NTM isolated from 172 household plumbing biofilms and soil samples from 62 non-patient households and 15 respiratory specimens. Although non-uniform geographic sampling and availability of patient information were limitations, Mycobacterium chimaera was found to be the dominant species in both environmental and respiratory specimens. In contrast to previous studies from the continental U.S., no Mycobacterium avium was identified. Mycobacterium intracellulare was found only in respiratory specimens and a soil sample. We conclude that Hawai'i's household water so...
We report the draft genome of Elizabethkingia strain ATCC 33958, which has been classified as Eli... more We report the draft genome of Elizabethkingia strain ATCC 33958, which has been classified as Elizabethkingia miricola . Similar to other Elizabethkingia species, the ATCC 33958 draft genome contains numerous β-lactamase genes. ATCC 33958 also harbors a urease gene cluster which supports classification as E. miricola .
Additional file 4: Figure S1. Relative locations of predicted prophages in M. absessus subsp. abs... more Additional file 4: Figure S1. Relative locations of predicted prophages in M. absessus subsp. absessus and M. avium. Prophages are colored by the host origin.
Additional file 3. This file contains 6 data tables used in the study. The Predicted_Prophages ta... more Additional file 3. This file contains 6 data tables used in the study. The Predicted_Prophages tab provides details about the predicted prophages including the genomic coordinates, cluster assignment, and the presence/absence of a bacterial virulence gene. The Predicted_Prophages_Edge_Cases lists the coordinates of prophages near the ends of contigs. The Bacterial_Genes tab represents the annotated output of bacterial genes (excluding bacterial virulence genes). The Virulence_Genes represents the annotated output of bacterial virulence genes. The Cluster_Virulence tab groups the predicted prophages by cluster and virulence status. The Virulence_Gene_Origins tab represents a count of the species origin of a virulence gene in the predicted prophages.
Additional file 7: Figure S4. Phylogeny of host M. chimaera and M. intracellulare genomes. The sh... more Additional file 7: Figure S4. Phylogeny of host M. chimaera and M. intracellulare genomes. The shaded boxes are located along an x axis, which lists the lettered PhagesDB clusters. The presence of prophage in a sample is noted by a shaded box in any column except NA/Control. No shading means the sample does not have a prophage in that lettered cluster. Statistical significance was not achieved using PERMANOVA on this tree (F = 1.12, p = 0.321).
Additional file 6: Figure S3. Phylogeny of host M. absessus subsp. massiliense genomes. The shade... more Additional file 6: Figure S3. Phylogeny of host M. absessus subsp. massiliense genomes. The shaded boxes are located along an x axis, which lists the lettered PhagesDB clusters. The presence of prophage in a sample is noted by a shaded box in any column except NA/Control. No shading means the sample does not have a prophage in that lettered cluster. Statistical significance was not achieved using PERMANOVA on this tree (F = 1.398, p = 0.225).
Mycobacterium chelonae is a rapidly growing opportunistic nontuberculous mycobacterial (NTM) spec... more Mycobacterium chelonae is a rapidly growing opportunistic nontuberculous mycobacterial (NTM) species that causes infections in humans and other hosts. Here, we report the draft genome sequence ofMycobacterium chelonae type strain ATCC 35752, con-sisting of 4.89Mbp, 63.96%GC content, 4,489 protein-coding genes, 48 tRNAs, and 3 rRNA genes.
AIMS Mycobacterium abscessus subsp. abscessus (MABS) is an emerging, opportunistic pathogen found... more AIMS Mycobacterium abscessus subsp. abscessus (MABS) is an emerging, opportunistic pathogen found globally in freshwater biofilms and soil. Typically, isolates are treated as a uniform group of organisms and very little is known about their comparative survival in healthy host cells. We posit that environmentally- and clinically-derived isolates, show differential infectivity in immune cells and resistance to innate defenses. METHODS AND RESULTS Six MABS isolates were tested including three water biofilm/soil and three sputum-derived isolates. A clinical MABS type strain and an environmental isolate of Arthrobacter were also included. MABS counts were significantly higher compared to Arthrobacter after co-culture with Acanthamoeba lenticulata, BEAS-2B epithelial cells, alveolar macrophages, and the THP-1 macrophage cell line. A rough sputum-derived MABS isolate emerged as an isolate with higher virulence compared to others tested, as both a pellicle and cord former, survivor in the human cell models tested, inducer of high and prolonged production of pro-inflammatory cytokines, and the capacity to evade LL-37. CONCLUSIONS Findings support intraspecies variation between MABS isolates. SIGNIFICANCE AND IMPACT OF STUDY These data indicate subversion of host immune defenses by environmental and clinical MABS isolates is nuanced and maybe isolate dependent, providing new information regarding the pathogenesis of NTM infections.
Mycobacterium avium complex (MAC) species constitute most mycobacteria infections in persons with... more Mycobacterium avium complex (MAC) species constitute most mycobacteria infections in persons with cystic fibrosis (CF) in the United States, but little is known about their genomic diversity or transmission. During 2016-2020, we performed whole-genome sequencing on 364 MAC isolates from 186 persons with CF from 42 cystic fibrosis care centers (CFCCs) across 23 states. We compared isolate genomes to identify instances of shared strains between persons with CF. Among persons with multiple isolates sequenced, 15/56 (27%) had >1 MAC strain type. Genomic comparisons revealed 18 clusters of highly similar isolates; 8 of these clusters had patients who shared CFCCs, which included 27/186 (15%) persons with CF. We provide genomic evidence of highly similar MAC strains shared among patients at the same CFCCs. Polyclonal infections and high genetic similarity between MAC isolates are consistent with multiple modes of acquisition for persons with CF to acquire MAC infections.
Nontuberculous mycobacteria (NTM) are environmental organisms that can cause opportunistic pulmon... more Nontuberculous mycobacteria (NTM) are environmental organisms that can cause opportunistic pulmonary disease with species diversity showing significant regional variation. In the United States, Hawai’i shows the highest rate of NTM pulmonary disease. The need for improved understanding of NTM reservoirs led us to identify NTM from patient respiratory specimens and compare NTM diversity between outdoor and indoor locations in Hawai’i. A total of 545 water biofilm samples were collected from 357 unique locations across Kaua’i (n = 51), O’ahu (n = 202), Maui (n = 159), and Hawai’i Island (n = 133) and divided into outdoor (n = 179) or indoor (n = 366) categories. rpoB sequence analysis was used to determine NTM species and predictive modeling applied to develop NTM risk maps based on geographic characteristics between environments. M. chimaera was frequently identified from respiratory and environmental samples followed by M. chelonae and M. abscessus; yet significantly less NTM were c...
Background The increasing incidence of drug resistance in tuberculosis and other infectious disea... more Background The increasing incidence of drug resistance in tuberculosis and other infectious diseases poses an escalating cause for concern, emphasizing the urgent need to devise robust computational and molecular methods identify drug resistant strains. Although machine learning-based approaches using whole-genome sequence data can facilitate the inference of drug resistance, current implementations do not optimally take advantage of information in public databases and are not robust for small sample sizes and mixed attribute types. Results In this paper we introduce the Composite MetaDistance method, an approach for feature selection and classification of high-dimensional, unbalanced datasets with mixed attribute features from various data sources. We introduce a mixed-attribute, multi-view distance function to calculate distances between samples, with optimal handling of nominal features and different feature views. We also introduce a novel feature set for drug resistance predict...
Globally and in the United States, the prevalence of NTM pulmonary disease—a potentially life-thr... more Globally and in the United States, the prevalence of NTM pulmonary disease—a potentially life-threatening but underdiagnosed chronic illness—is prominently rising. While NTM are ubiquitous in the environment, including in soil, the specific soil components that promote or inhibit NTM growth have not been elucidated. We hypothesized that NTM culture-positive soil contains minerals that promote NTM growth in vitro . Because Hawai’i is a hot spot for NTM and a unique geographic archipelago, we examined the composition of Hawai’i soil and identified individual clay, iron, and manganese minerals associated with NTM. Next, individual components were evaluated for their ability to directly modulate NTM growth in culture. In general, gibbsite and some manganese oxides were shown to decrease NTM, whereas iron-containing minerals were associated with higher NTM counts. These data provide new information to guide future analyses of soil-associated factors impacting persistence of these soil ba...
Recent studies have characterized a dominant clone (Clone 1) of Mycobacterium abscessus subspecie... more Recent studies have characterized a dominant clone (Clone 1) of Mycobacterium abscessus subspecies massiliense (M. massiliense) associated with high prevalence in cystic fibrosis (CF) patients, pulmonary outbreaks in the United States (US) and United Kingdom (UK), and a Brazilian epidemic of skin infections. The prevalence of Clone 1 in non-CF patients in the US and the relationship of sporadic US isolates to outbreak clones are not known. We surveyed a reference US Mycobacteria Laboratory and a US biorepository of CF-associated Mycobacteria isolates for Clone 1. We then compared genomic variation and antimicrobial resistance (AMR) mutations between sporadic non-CF, CF, and outbreak Clone 1 isolates. Among reference lab samples, 57/147 (39%) of patients with M. massiliense had Clone 1, including pulmonary and extrapulmonary infections, compared to 11/64 (17%) in the CF isolate biorepository. Core and pan genome analyses revealed that outbreak isolates had similar numbers of single n...
Short-term interaction between Acanthamoeba and M. avium has been demonstrated to increase infect... more Short-term interaction between Acanthamoeba and M. avium has been demonstrated to increase infectivity in human and murine models of infection, establishing the paradigm that amoebae “train” M. avium in the environment by selecting for phenotypes capable of enduring in human cells. We investigated this phenomenon further by determining the consequence of long-term amoebae adaptation on M. avium subsp. hominissuis persistence in host cells.
Rationale Mycobacterium abscessus is a significant threat to individuals with cystic fibrosis (CF... more Rationale Mycobacterium abscessus is a significant threat to individuals with cystic fibrosis (CF) due to innate drug resistance and potential transmission between patients. Recent studies described global dominant circulating clones of M. abscessus, but detailed genomic surveys have not yet been described for the United States (US). Objectives We examined the genetic diversity of respiratory M. abscessus isolates from US patients with CF and evaluated the potential for transmission events within CF Care Centers. Methods Whole genome sequencing was performed on 558 M. abscessus isolates from 266 patients with CF attending 48 CF Care Centers in 28 US states as part of a nationwide surveillance program. US isolates were also compared to 64 isolate genomes from 13 previous studies to evaluate the prevalence of recently described dominant circulating clones. Results More than half of study patients with CF and M. abscessus had isolates within four dominant clones; two clones of M. abscessus subsp. abscessus (MAB) and two clones of M. abscessus subsp. massiliense (MMAS). Acquired drug resistance mutations for aminoglycosides and macrolides were rare in the isolate population, and they were not significantly enriched in dominant clones compared to unclustered isolates. For a subset of 55 patients, there was no relationship between dominant clones and diagnosis of active lung disease (p=1.0). Twenty-nine clusters of genetically similar MAB isolates and eight clusters of genetically similar MMAS isolates were identified. Overall, 28/204 (14%) patients with MAB and 15/64 (23%) with MMAS had genetically similar isolates to at least one other patient at the same CF Care Center. Genetically similar isolates were also found between 60/204 (29%) patients with MAB and 19/64 (30%) with MMAS from different geographic locations. Conclusions Our study reveals the predominant genotypes of M. abscessus and frequency of shared strains between patients in US CF Care Centers. Integrated epidemiological and environmental studies would help to explain the widespread presence of dominant clones in the US, including the potential for broad distribution in the environment. Single site studies using systematic, evidence-based approaches will be needed to establish the contributions of healthcare-associated transmission versus shared environmental exposures.
Whole-genome sequencing (WGS) has recently been used to investigate acquisition of Mycobacterium ... more Whole-genome sequencing (WGS) has recently been used to investigate acquisition of Mycobacterium abscessus . Investigators have reached conflicting conclusions about the meaning of genetic distances for interpretation of person-to-person transmission.
International journal of systematic and evolutionary microbiology, Jan 15, 2017
A novel slowly growing, non-chromogenic species of the class Actinobacteria was isolated from a h... more A novel slowly growing, non-chromogenic species of the class Actinobacteria was isolated from a human respiratory sample in Nebraska, USA, in 2012. Analysis of the internal transcribed spacer sequence supported placement into the genus Mycobacterium with high sequence similarity to a previously undescribed strain isolated from a patient respiratory sample from Oregon, USA, held in a collection in Colorado, USA, in 2000. The two isolates were subjected to phenotypic testing and whole genome sequencing and found to be indistinguishable. The bacteria were acid-fast stain-positive, rod-shaped and exhibited growth after 7-10 days on solid media at temperatures ranging from 25 to 42°C. Colonies were non-pigmented, rough and slightly raised. Analyses of matrix-assisted laser desorption ionization time-of-flight profiles showed no matches against a reference library of 130 mycobacterial species. Full-length 16S rRNA gene sequences were identical for the two isolates, the average nucleotide ...
Lung disease caused by nontuberculous mycobacteria (NTM) is an emerging infectious disease of glo... more Lung disease caused by nontuberculous mycobacteria (NTM) is an emerging infectious disease of global significance. Epidemiologic studies have shown the Hawaiian Islands have the highest prevalence of NTM lung infections in the United States. However, potential environmental reservoirs and species diversity have not been characterized. In this cross-sectional study, we describe molecular and phylogenetic comparisons of NTM isolated from 172 household plumbing biofilms and soil samples from 62 non-patient households and 15 respiratory specimens. Although non-uniform geographic sampling and availability of patient information were limitations, Mycobacterium chimaera was found to be the dominant species in both environmental and respiratory specimens. In contrast to previous studies from the continental U.S., no Mycobacterium avium was identified. Mycobacterium intracellulare was found only in respiratory specimens and a soil sample. We conclude that Hawai'i's household water so...
We report the draft genome of Elizabethkingia strain ATCC 33958, which has been classified as Eli... more We report the draft genome of Elizabethkingia strain ATCC 33958, which has been classified as Elizabethkingia miricola . Similar to other Elizabethkingia species, the ATCC 33958 draft genome contains numerous β-lactamase genes. ATCC 33958 also harbors a urease gene cluster which supports classification as E. miricola .
Additional file 4: Figure S1. Relative locations of predicted prophages in M. absessus subsp. abs... more Additional file 4: Figure S1. Relative locations of predicted prophages in M. absessus subsp. absessus and M. avium. Prophages are colored by the host origin.
Additional file 3. This file contains 6 data tables used in the study. The Predicted_Prophages ta... more Additional file 3. This file contains 6 data tables used in the study. The Predicted_Prophages tab provides details about the predicted prophages including the genomic coordinates, cluster assignment, and the presence/absence of a bacterial virulence gene. The Predicted_Prophages_Edge_Cases lists the coordinates of prophages near the ends of contigs. The Bacterial_Genes tab represents the annotated output of bacterial genes (excluding bacterial virulence genes). The Virulence_Genes represents the annotated output of bacterial virulence genes. The Cluster_Virulence tab groups the predicted prophages by cluster and virulence status. The Virulence_Gene_Origins tab represents a count of the species origin of a virulence gene in the predicted prophages.
Additional file 7: Figure S4. Phylogeny of host M. chimaera and M. intracellulare genomes. The sh... more Additional file 7: Figure S4. Phylogeny of host M. chimaera and M. intracellulare genomes. The shaded boxes are located along an x axis, which lists the lettered PhagesDB clusters. The presence of prophage in a sample is noted by a shaded box in any column except NA/Control. No shading means the sample does not have a prophage in that lettered cluster. Statistical significance was not achieved using PERMANOVA on this tree (F = 1.12, p = 0.321).
Additional file 6: Figure S3. Phylogeny of host M. absessus subsp. massiliense genomes. The shade... more Additional file 6: Figure S3. Phylogeny of host M. absessus subsp. massiliense genomes. The shaded boxes are located along an x axis, which lists the lettered PhagesDB clusters. The presence of prophage in a sample is noted by a shaded box in any column except NA/Control. No shading means the sample does not have a prophage in that lettered cluster. Statistical significance was not achieved using PERMANOVA on this tree (F = 1.398, p = 0.225).
Mycobacterium chelonae is a rapidly growing opportunistic nontuberculous mycobacterial (NTM) spec... more Mycobacterium chelonae is a rapidly growing opportunistic nontuberculous mycobacterial (NTM) species that causes infections in humans and other hosts. Here, we report the draft genome sequence ofMycobacterium chelonae type strain ATCC 35752, con-sisting of 4.89Mbp, 63.96%GC content, 4,489 protein-coding genes, 48 tRNAs, and 3 rRNA genes.
AIMS Mycobacterium abscessus subsp. abscessus (MABS) is an emerging, opportunistic pathogen found... more AIMS Mycobacterium abscessus subsp. abscessus (MABS) is an emerging, opportunistic pathogen found globally in freshwater biofilms and soil. Typically, isolates are treated as a uniform group of organisms and very little is known about their comparative survival in healthy host cells. We posit that environmentally- and clinically-derived isolates, show differential infectivity in immune cells and resistance to innate defenses. METHODS AND RESULTS Six MABS isolates were tested including three water biofilm/soil and three sputum-derived isolates. A clinical MABS type strain and an environmental isolate of Arthrobacter were also included. MABS counts were significantly higher compared to Arthrobacter after co-culture with Acanthamoeba lenticulata, BEAS-2B epithelial cells, alveolar macrophages, and the THP-1 macrophage cell line. A rough sputum-derived MABS isolate emerged as an isolate with higher virulence compared to others tested, as both a pellicle and cord former, survivor in the human cell models tested, inducer of high and prolonged production of pro-inflammatory cytokines, and the capacity to evade LL-37. CONCLUSIONS Findings support intraspecies variation between MABS isolates. SIGNIFICANCE AND IMPACT OF STUDY These data indicate subversion of host immune defenses by environmental and clinical MABS isolates is nuanced and maybe isolate dependent, providing new information regarding the pathogenesis of NTM infections.
Mycobacterium avium complex (MAC) species constitute most mycobacteria infections in persons with... more Mycobacterium avium complex (MAC) species constitute most mycobacteria infections in persons with cystic fibrosis (CF) in the United States, but little is known about their genomic diversity or transmission. During 2016-2020, we performed whole-genome sequencing on 364 MAC isolates from 186 persons with CF from 42 cystic fibrosis care centers (CFCCs) across 23 states. We compared isolate genomes to identify instances of shared strains between persons with CF. Among persons with multiple isolates sequenced, 15/56 (27%) had >1 MAC strain type. Genomic comparisons revealed 18 clusters of highly similar isolates; 8 of these clusters had patients who shared CFCCs, which included 27/186 (15%) persons with CF. We provide genomic evidence of highly similar MAC strains shared among patients at the same CFCCs. Polyclonal infections and high genetic similarity between MAC isolates are consistent with multiple modes of acquisition for persons with CF to acquire MAC infections.
Nontuberculous mycobacteria (NTM) are environmental organisms that can cause opportunistic pulmon... more Nontuberculous mycobacteria (NTM) are environmental organisms that can cause opportunistic pulmonary disease with species diversity showing significant regional variation. In the United States, Hawai’i shows the highest rate of NTM pulmonary disease. The need for improved understanding of NTM reservoirs led us to identify NTM from patient respiratory specimens and compare NTM diversity between outdoor and indoor locations in Hawai’i. A total of 545 water biofilm samples were collected from 357 unique locations across Kaua’i (n = 51), O’ahu (n = 202), Maui (n = 159), and Hawai’i Island (n = 133) and divided into outdoor (n = 179) or indoor (n = 366) categories. rpoB sequence analysis was used to determine NTM species and predictive modeling applied to develop NTM risk maps based on geographic characteristics between environments. M. chimaera was frequently identified from respiratory and environmental samples followed by M. chelonae and M. abscessus; yet significantly less NTM were c...
Background The increasing incidence of drug resistance in tuberculosis and other infectious disea... more Background The increasing incidence of drug resistance in tuberculosis and other infectious diseases poses an escalating cause for concern, emphasizing the urgent need to devise robust computational and molecular methods identify drug resistant strains. Although machine learning-based approaches using whole-genome sequence data can facilitate the inference of drug resistance, current implementations do not optimally take advantage of information in public databases and are not robust for small sample sizes and mixed attribute types. Results In this paper we introduce the Composite MetaDistance method, an approach for feature selection and classification of high-dimensional, unbalanced datasets with mixed attribute features from various data sources. We introduce a mixed-attribute, multi-view distance function to calculate distances between samples, with optimal handling of nominal features and different feature views. We also introduce a novel feature set for drug resistance predict...
Globally and in the United States, the prevalence of NTM pulmonary disease—a potentially life-thr... more Globally and in the United States, the prevalence of NTM pulmonary disease—a potentially life-threatening but underdiagnosed chronic illness—is prominently rising. While NTM are ubiquitous in the environment, including in soil, the specific soil components that promote or inhibit NTM growth have not been elucidated. We hypothesized that NTM culture-positive soil contains minerals that promote NTM growth in vitro . Because Hawai’i is a hot spot for NTM and a unique geographic archipelago, we examined the composition of Hawai’i soil and identified individual clay, iron, and manganese minerals associated with NTM. Next, individual components were evaluated for their ability to directly modulate NTM growth in culture. In general, gibbsite and some manganese oxides were shown to decrease NTM, whereas iron-containing minerals were associated with higher NTM counts. These data provide new information to guide future analyses of soil-associated factors impacting persistence of these soil ba...
Recent studies have characterized a dominant clone (Clone 1) of Mycobacterium abscessus subspecie... more Recent studies have characterized a dominant clone (Clone 1) of Mycobacterium abscessus subspecies massiliense (M. massiliense) associated with high prevalence in cystic fibrosis (CF) patients, pulmonary outbreaks in the United States (US) and United Kingdom (UK), and a Brazilian epidemic of skin infections. The prevalence of Clone 1 in non-CF patients in the US and the relationship of sporadic US isolates to outbreak clones are not known. We surveyed a reference US Mycobacteria Laboratory and a US biorepository of CF-associated Mycobacteria isolates for Clone 1. We then compared genomic variation and antimicrobial resistance (AMR) mutations between sporadic non-CF, CF, and outbreak Clone 1 isolates. Among reference lab samples, 57/147 (39%) of patients with M. massiliense had Clone 1, including pulmonary and extrapulmonary infections, compared to 11/64 (17%) in the CF isolate biorepository. Core and pan genome analyses revealed that outbreak isolates had similar numbers of single n...
Short-term interaction between Acanthamoeba and M. avium has been demonstrated to increase infect... more Short-term interaction between Acanthamoeba and M. avium has been demonstrated to increase infectivity in human and murine models of infection, establishing the paradigm that amoebae “train” M. avium in the environment by selecting for phenotypes capable of enduring in human cells. We investigated this phenomenon further by determining the consequence of long-term amoebae adaptation on M. avium subsp. hominissuis persistence in host cells.
Rationale Mycobacterium abscessus is a significant threat to individuals with cystic fibrosis (CF... more Rationale Mycobacterium abscessus is a significant threat to individuals with cystic fibrosis (CF) due to innate drug resistance and potential transmission between patients. Recent studies described global dominant circulating clones of M. abscessus, but detailed genomic surveys have not yet been described for the United States (US). Objectives We examined the genetic diversity of respiratory M. abscessus isolates from US patients with CF and evaluated the potential for transmission events within CF Care Centers. Methods Whole genome sequencing was performed on 558 M. abscessus isolates from 266 patients with CF attending 48 CF Care Centers in 28 US states as part of a nationwide surveillance program. US isolates were also compared to 64 isolate genomes from 13 previous studies to evaluate the prevalence of recently described dominant circulating clones. Results More than half of study patients with CF and M. abscessus had isolates within four dominant clones; two clones of M. abscessus subsp. abscessus (MAB) and two clones of M. abscessus subsp. massiliense (MMAS). Acquired drug resistance mutations for aminoglycosides and macrolides were rare in the isolate population, and they were not significantly enriched in dominant clones compared to unclustered isolates. For a subset of 55 patients, there was no relationship between dominant clones and diagnosis of active lung disease (p=1.0). Twenty-nine clusters of genetically similar MAB isolates and eight clusters of genetically similar MMAS isolates were identified. Overall, 28/204 (14%) patients with MAB and 15/64 (23%) with MMAS had genetically similar isolates to at least one other patient at the same CF Care Center. Genetically similar isolates were also found between 60/204 (29%) patients with MAB and 19/64 (30%) with MMAS from different geographic locations. Conclusions Our study reveals the predominant genotypes of M. abscessus and frequency of shared strains between patients in US CF Care Centers. Integrated epidemiological and environmental studies would help to explain the widespread presence of dominant clones in the US, including the potential for broad distribution in the environment. Single site studies using systematic, evidence-based approaches will be needed to establish the contributions of healthcare-associated transmission versus shared environmental exposures.
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