scholarly journals Genome reorganization during emergence of host-associated Mycobacterium abscessus

2021 ◽  
Vol 7 (12) ◽  
Author(s):  
Lindsey L. Bohr ◽  
Madison A. Youngblom ◽  
Vegard Eldholm ◽  
Caitlin S. Pepperell
Keyword(s):  
Type Species ◽  
Host Adaptation ◽  
Mycobacterium Abscessus ◽  
Evolutionary Trajectory ◽  
Selection Pressures ◽  
Content Type ◽  
Evolutionary Forces ◽  
Link Type ◽  
Genome Reorganization ◽  
Geographical Regions

Mycobacterium abscessus is a rapid growing, free-living species of bacterium that also causes lung infections in humans. Human infections are usually acquired from the environment; however, dominant circulating clones (DCCs) have emerged recently in both M. abscessus subsp. massiliense and subsp. abscessus that appear to be transmitted among humans and are now globally distributed. These recently emerged clones are potentially informative about the ecological and evolutionary mechanisms of pathogen emergence and host adaptation. The geographical distribution of DCCs has been reported, but the genomic processes underlying their transition from environmental bacterium to human pathogen are not well characterized. To address this knowledge gap, we delineated the structure of M. abscessus subspecies abscessus and massiliense using genomic data from 200 clinical isolates of M. abscessus from seven geographical regions. We identified differences in overall patterns of lateral gene transfer (LGT) and barriers to LGT between subspecies and between environmental and host-adapted bacteria. We further characterized genome reorganization that accompanied bacterial host adaptation, inferring selection pressures acting at both genic and intergenic loci. We found that both subspecies encode an expansive pangenome with many genes at rare frequencies. Recombination appears more frequent in M. abscessus subsp. massiliense than in subsp. abscessus, consistent with prior reports. We found evidence suggesting that phage are exchanged between subspecies, despite genetic barriers evident elsewhere throughout the genome. Patterns of LGT differed according to niche, with less LGT observed among host-adapted DCCs versus environmental bacteria. We also found evidence suggesting that DCCs are under distinct selection pressures at both genic and intergenic sites. Our results indicate that host adaptation of M. abscessus was accompanied by major changes in genome evolution, including shifts in the apparent frequency of LGT and impacts of selection. Differences were evident among the DCCs as well, which varied in the degree of gene content remodelling, suggesting they were placed differently along the evolutionary trajectory toward host adaptation. These results provide insight into the evolutionary forces that reshape bacterial genomes as they emerge into the pathogenic niche.

Environment in the lung of cystic fibrosis patients stimulates the expression of biofilm phenotype in Mycobacterium abscessus

2022 ◽  
Vol 71 (1) ◽  
Author(s):  
Bailey F. Keefe ◽  
Luiz E. Bermudez
Keyword(s):  
Cystic Fibrosis ◽  
Host Cell ◽  
Biofilm Formation ◽  
Type Species ◽  
Divalent Cations ◽  
Mycobacterium Abscessus ◽  
Content Type ◽  
Link Type ◽  
Populations At Risk

Introduction. Pulmonary infections caused by organisms of the Mycobacterium abscessus complex are increasingly prevalent in populations at risk, such as patients with cystic fibrosis, bronchiectasis and emphysema. Hypothesis. M. abscessus infection of the lung is not observed in immunocompetent individuals, which raises the possibility that the compromised lung environment is a suitable niche for the pathogen to thrive in due to the overproduction of mucus and high amounts of host cell lysis. Aim. Evaluate the ability of M. abscessus to form biofilm and grow utilizing in vitro conditions as seen in immunocompromised lungs of patients. Methodology. We compared biofilm formation and protein composition in the presence and absence of synthetic cystic fibrosis medium (SCFM) and evaluated the bacterial growth when exposed to human DNA. Results. M. abscessus is capable of forming biofilm in SCFM. By eliminating single components found in the medium, it became clear that magnesium works as a signal for the biofilm formation, and chelation of the divalent cations resulted in the suppression of biofilm formation. Investigation of the specific proteins expressed in the presence of SCFM and in the presence of SCFM lacking magnesium revealed many different proteins between the conditions. M. abscessus also exhibited growth in SCFM and in the presence of host cell DNA, although the mechanism of DNA utilization remains unclear. Conclusions. In vitro conditions mimicking the airways of patients with cystic fibrosis appear to facilitate M. abscessus establishment of infection, and elimination of magnesium from the environment may affect the ability of the pathogen to establish infection.

scholarly journals Descriptions of Rhodopseudomonas parapalustris sp. nov., Rhodopseudomonas harwoodiae sp. nov. and Rhodopseudomonas pseudopalustris sp. nov., and emended description of Rhodopseudomonas palustris

2012 ◽  
Vol 62 (Pt_8) ◽  
pp. 1790-1798 ◽  
Author(s):  
V. Venkata Ramana ◽  
S. Kalyana Chakravarthy ◽  
P. Shalem Raj ◽  
B. Vinay Kumar ◽  
E. Shobha ◽  
...  
Keyword(s):  
Dna Hybridization ◽  
Type Species ◽  
Novel Species ◽  
Rhodopseudomonas Palustris ◽  
Rrna Gene ◽  
Content Type ◽  
Link Type ◽  
Geographical Regions ◽  
Emended Description ◽  
Type Strains

Four strains (JA310T, JA531T, JA447 and JA490) of red to reddish brown pigmented, rod-shaped, motile and budding phototrophic bacteria were isolated from soil and freshwater sediment samples from different geographical regions of India. All strains contained bacteriochlorophyll a and carotenoids of the spirilloxanthin series. The major cellular fatty acid of strains JA310T and JA531T was C18 : 1ω7c, the quinone was Q-10 and polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, an aminohopanoid and an unidentified aminolipid. Phylogenetic analysis based on 16S rRNA gene sequences showed that all strains clustered with species of the genus Rhodopseudomonas in the class Alphaproteobacteria . Strains JA531T, JA447 and JA490 were genotypically (>80 % related based on DNA–DNA hybridization) and phenotypically closely related to each other and the three strains were distinct from strain JA310T (33 % related). Furthermore, all four strains had less than 48 % relatedness (DNA–DNA hybridization) with type strains of members of the genus Rhodopseudomonas , i.e. Rhodopseudomonas palustris ATCC 17001T, Rhodopseudomonas faecalis JCM 11668T and Rhodopseudomonas rhenobacensis DSM 12706T. The genomic DNA G+C contents of strains JA310T and JA531T were 63.8 and 62.4 mol%, respectively. On the basis of phenotypic, chemotaxonomic and molecular genetic evidence, it is proposed that strains JA310T ( = NBRC 106083T = KCTC 5839T) and JA531T ( = NBRC 107575T = KCTC 5841T) be classified as the type strains of two novel species of the genus Rhodopseudomonas , Rhodopseudomonas parapalustris sp. nov. and Rhodopseudomonas harwoodiae sp. nov., respectively. In addition, we propose that strain DSM 123T ( = NBRC 100419T) represents a novel species, Rhodopseudomonas pseudopalustris sp. nov., since this strain differs genotypically and phenotypically from R. palustris ATCC 17001T and other members of the genus Rhodopseudomonas . An emended description of R. palustris is also provided.

scholarly journals A genuine mycobacterial thermophile: Mycobacterium hassiacum growth, survival and GpgS stability at near-pasteurization temperatures

Microbiology ◽  
2020 ◽  
Vol 166 (5) ◽  
pp. 474-483 ◽  
Author(s):  
Susana Alarico ◽  
Daniela Nunes-Costa ◽  
Alexandra Silva ◽  
Mafalda Costa ◽  
Sandra Macedo-Ribeiro ◽  
...  
Keyword(s):  
Drug Targets ◽  
Type Species ◽  
Mycobacterium Abscessus ◽  
Water Supply Systems ◽  
Content Type ◽  
Link Type ◽  
Food And Drink ◽  
Supply Systems ◽  
Potential Drug Targets ◽  
Resistance To Heat

Mycobacterium hassiacum is so far the most thermophilic among mycobacteria as it grows optimally at 50 °C and up to 65 °C in a glycerol-based medium, as verified in this study. Since this and other nontuberculous mycobacteria (NTM) thrive in diverse natural and artificial environments, from where they may access and infect humans, we deemed essential to probe M. hassiacum resistance to heat, a strategy routinely used to control microbial growth in water-supply systems, as well as in the food and drink industries. In addition to possibly being a threat in its own right in rare occasions, M. hassiacum is also a good surrogate for studying other NTM species more often associated with opportunistic infection, namely Mycobacterium avium and Mycobacterium abscessus as well as their strictly pathogenic counterparts Mycobacterium tuberculosis and Mycobacterium leprae . In this regard, this thermophilic species is likely to be useful as a source of stable proteins that may provide more detailed structures of potential drug targets. Here, we investigate M. hassiacum growth at near-pasteurization temperatures and at different pHs and also characterize its thermostable glucosyl-3-phosphoglycerate synthase (GpgS), an enzyme considered essential for M. tuberculosis growth and associated with both nitrogen starvation and thermal stress in different NTM species.

scholarly journals Molecular epidemiology and phylogenomic analysis of Mycobacterium abscessus clinical isolates in an Asian population

2021 ◽  
Vol 7 (11) ◽  
Author(s):  
Ka Lip Chew ◽  
Sophie Octavia ◽  
Roland Jureen ◽  
Oon Tek Ng ◽  
Kalisvar Marimuthu ◽  
...  
Keyword(s):  
Virulence Factors ◽  
Type Species ◽  
Asian Population ◽  
Bioinformatic Analysis ◽  
Mycobacterium Abscessus ◽  
Phylogenomic Analysis ◽  
Pathogenic Potential ◽  
Content Type ◽  
Link Type ◽  
Sequence Types

Mycobacterium abscessus comprises three subspecies: M. abscessus subsp. abscessus , M. abscessus subsp. bolletii , and M. abscessus subsp. massiliense . These closely related strains are typically multi-drug-resistant and can cause difficult-to-treat infections. Dominant clusters of isolates with increased pathogenic potential have been demonstrated in pulmonary infections in the global cystic fibrosis (CF) population. An investigation was performed on isolates cultured from an Asian, predominantly non-CF population to explore the phylogenomic relationships within our population and compare it to global M. abscessus isolates. Whole-genome-sequencing was performed on M. abscessus isolates between 2017 and 2019. Bioinformatic analysis was performed to determine multi-locus-sequence-type, to establish the phylogenetic relationships between isolates, and to identify virulence and resistance determinants in these isolates. A total of 210 isolates were included, of which 68.5 % (144/210) were respiratory samples. These isolates consisted of 140 (66.6 %) M . abscessus subsp. massiliense , 67 (31.9 %) M . abscessus subsp. abscessus, and three (1.4 %) M . abscessus subsp. bolletii . Dominant sequence-types in our population were similar to those of global CF isolates, but SNP differences in our population were comparatively wider despite the isolates being from the same geographical region. ESX (ESAT-6 secretory) cluster three appeared to occur most commonly in ST4 and ST6 M. abscessus subsp. massiliense , but other virulence factors did not demonstrate an association with isolate subspecies or sample source. We demonstrate that although similar predominant sequence-types are seen in our patient population, cross-transmission is absent. The risk of patient-to-patient transmission appears to be largely limited to the vulnerable CF population, indicating infection from environmental sources remains more common than human-to-human transmission. Resistance and virulence factors are largely consistent across the subspecies with the exception of clarithromycin susceptibility and ESX-3.

scholarly journals Antibacterial activity of high-dose nitric oxide against pulmonary Mycobacterium abscessus disease

2020 ◽  
Vol 2 (9) ◽  
Author(s):  
Kristijan Bogdanovski ◽  
Trisha Chau ◽  
Chevalia J. Robinson ◽  
Sandra D. MacDonald ◽  
Ann M. Peterson ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Antibacterial Activity ◽  
Type Species ◽  
Mycobacterium Abscessus ◽  
Clinical Isolates ◽  
Content Type ◽  
Link Type ◽  
Susceptibility Tests ◽  
Inhaled No

Introduction. Mycobacterium abscessus is an emerging pulmonary pathogen with limited treatment options. Nitric oxide (NO) demonstrates antibacterial activity against various bacterial species, including mycobacteria. In this study, we evaluated the effect of adjunctive inhaled NO therapy, using a novel NO generator, in a CF patient with pulmonary M. abscessus disease, and examined heterogeneity of response to NO in vitro. Methods. In the compassionate-use treatment, a 24-year-old CF patient with pulmonary M. abscessus was treated with two courses of adjunctive intermittent NO, first at 160 p.p.m. for 21 days and subsequently by escalating the dose up to 240 p.p.m. for 8 days. Methemoglobin, pulmonary function, 6 min walk distance (6MWD), qualify of life and sputum microbiology were assessed. In vitro susceptibility tests were performed against patient’s isolate and comparison clinical isolates and quantified by Hill’s slopes calculated from time–kill curves. Results. M. abscessus lung infection eradication was not achieved, but improvements in selected qualify of life domains, lung function and 6MWD were observed during the study. Inhaled NO was well tolerated at 160 p.p.m. Dosing at 240 p.p.m. was stopped due to adverse symptoms, although methemoglobin levels remained within safety thresholds. In vitro susceptibility tests showed a dose-dependent NO effect on M. abscessus susceptibility and significant heterogeneity in response between M. abscessus clinical isolates. The patient’s isolate was found to be the least susceptible strain in vitro. Conclusion. These results demonstrate heterogeneity in M. abscessus susceptibility to NO and suggest that longer treatment regimens could be required to see the reduction or eradication of more resistant pulmonary strains.

scholarly journals Intraspecies plasmid and genomic variation of Mycobacterium kubicae revealed by the complete genome sequences of two clinical isolates

2020 ◽  
Author(s):  
Jo Hendrix ◽  
L. Elaine Epperson ◽  
David Durbin ◽  
Jennifer R. Honda ◽  
Michael Strong
Keyword(s):  
Type Species ◽  
Mycobacterium Abscessus ◽  
Genomic Variation ◽  
Diagnostic Methods ◽  
Pathogenic Potential ◽  
Circular Chromosome ◽  
Content Type ◽  
Link Type ◽  
Complete Genomes ◽  
Long Read

Mycobacterium kubicae is 1 of nearly 200 species of nontuberculous mycobacteria (NTM), environmental micro-organisms that in some situations can infect humans and cause severe lung, skin and soft tissue infections. Although numerous studies have investigated the genetic variation among prevalent clinical NTM species, including Mycobacterium abscessus and Mycobacterium avium , many of the less common but clinically relevant NTM species, including M. kubicae , still lack complete genomes to serve as a comparative reference. Well-characterized representative genomes for each NTM species are important both for investigating the pathogenic potential of NTM, as well as for use in diagnostic methods, even for species that less frequently cause human disease. Here, we report the complete genomes of two M. kubicae strains, isolated from two unrelated patients. Hybrid short-read and long-read sequencing and assembly, using sequence reads from Illumina and Oxford Nanopore Technologies platforms, were utilized to resolve the chromosome and plasmid sequences of each isolate. The genome of NJH_MKUB1 had 5135 coding sequences (CDSs), a circular chromosome of length 5.3 Mb and two plasmids. The genome of NJH_MKUB2 had 5957 CDSs, a circular chromosome of 6.0 Mb and five plasmids. We compared our completed genomic assemblies to four recently released draft genomes of M. kubicae in order to better understand intraspecies genomic conservation and variability. We also identified genes implicated in drug resistance, virulence and persistence in the M. kubicae chromosome and plasmids. Virulence factors encoded in the genome and in the plasmids of M. kubicae provide a foundation for investigating how opportunistic environmental NTM may cause disease.

Development of a nucleic acid chromatography assay for the detection of commonly isolated rapidly growing mycobacteria

2021 ◽  
Vol 70 (12) ◽  
Author(s):  
Yuriko Igarashi ◽  
Kinuyo Chikamatsu ◽  
Sotaro Sano ◽  
Shigehiko Miyamoto ◽  
Akio Aono ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Type Species ◽  
Target Genes ◽  
Mycobacterium Abscessus ◽  
Heat Denaturation ◽  
Mycobacterium Fortuitum ◽  
Mycobacterium Chelonae ◽  
Content Type ◽  
Rapidly Growing Mycobacteria ◽  
Link Type

Introduction. Non-tuberculosis mycobacterium infections are increasing worldwide, including those caused by rapidly growing mycobacteria (RGM). Gap Statement. The identification of the aetiological agent in the context of infections is essential for the adoption of an adequate therapeutic approach. However, the methods for the rapid distinction of different RGM species are less than optimal. Aim. To develop a nucleic acid chromatography kit to identify clinically common RGM. Methodology. We tried to develop a nucleic acid chromatography kit designed to detect four RGM species (including three subspecies) i.e. Mycobacterium abscessus subsp. abscessus , Mycobacterium abscessus subsp. bolletii (detected as M. abscessus/bolletii) Mycobacterium abscessus subsp. massiliense , Mycobacterium fortuitum , Mycobacterium chelonae and Mycobacterium peregrinum . The amplified target genes for each species/subspecies using multiplex PCR were analysed using a nucleic acid chromatography assay. Results. Among the 159 mycobacterial type strains and 70 RGM clinical isolates tested, the developed assay correctly identified all relevant RGM without any cross-reactivity or false-negatives. The limits of detection for each species were approximately 0.2 pg µl-1. Conclusion. The rapid and simple nucleic acid chromatography method developed here, which does not involve heat denaturation, may contribute to the rapid identification and treatment of RGM infections.

scholarly journals Compromised longevity due to Mycobacterium abscessus pulmonary disease in lungs scarred by tuberculosis

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Urvashi B. Singh ◽  
Rojaleen Das ◽  
Prajowl Shrestha ◽  
Kiran Bala ◽  
Pooja Pandey ◽  
...  
Keyword(s):  
Pulmonary Disease ◽  
Type Species ◽  
Mycobacterium Abscessus ◽  
Combination Regimen ◽  
Disease Treatment ◽  
Content Type ◽  
Link Type ◽  
Previously Treated ◽  
Stopping Treatment

Structural lung diseases or scarring related to prior infections such as tuberculosis (TB) are risk factors for the development of invasive nontuberculous mycobacterial (NTM) pulmonary infections, such as Mycobacterium abscessus . M. abscessus is intrinsically resistant to many antibiotics and in vitro susceptibility correlates poorly with clinical response, especially in pulmonary disease. Treatment is often difficult due to the lack of effective antibiotic regimens. We present a case of a 56-year-old male previously treated for TB, with presumed exacerbation, who was diagnosed after much delay with pulmonary M. abscessus disease and subsequently failed initial treatment with an empirical antibiotic regimen. When placed on a synergistic combination regimen that included amikacin, linezolid, clarithromycin, ethambutol and faropenem, the patient showed a favourable response and was culture-negative for over 12 months when the treatment was stopped as per American Thoracic Society (ATS) recommendations. Unfortunately, he developed recurrent symptoms and died 9 months after stopping treatment, following an acute exacerbation of fever and respiratory failure.

scholarly journals A species-wide genetic atlas of antimicrobial resistance in Clostridioides difficile

2021 ◽  
Vol 7 (11) ◽  
Author(s):  
Korakrit Imwattana ◽  
César Rodríguez ◽  
Thomas V. Riley ◽  
Daniel R. Knight
Keyword(s):  
Antimicrobial Resistance ◽  
Type Species ◽  
Strong Association ◽  
Tetracycline Resistance ◽  
Multidrug Resistant ◽  
Fluoroquinolone Resistance ◽  
Content Type ◽  
Link Type ◽  
Clostridioides Difficile ◽  
Geographical Regions

Antimicrobial resistance (AMR) plays an important role in the pathogenesis and spread of Clostridioides difficile infection (CDI), the leading healthcare-related gastrointestinal infection in the world. An association between AMR and CDI outbreaks is well documented, however, data is limited to a few ‘epidemic’ strains in specific geographical regions. Here, through detailed analysis of 10 330 publicly-available C. difficile genomes from strains isolated worldwide (spanning 270 multilocus sequence types (STs) across all known evolutionary clades), this study provides the first species-wide snapshot of AMR genomic epidemiology in C. difficile . Of the 10 330 C . difficile genomes, 4532 (43.9 %) in 89 STs across clades 1–5 carried at least one genotypic AMR determinant, with 901 genomes (8.7 %) carrying AMR determinants for three or more antimicrobial classes (multidrug-resistant, MDR). No AMR genotype was identified in any strains belonging to the cryptic clades. C. difficile from Australia/New Zealand had the lowest AMR prevalence compared to strains from Asia, Europe and North America (P<0.0001). Based on the phylogenetic clade, AMR prevalence was higher in clades 2 (84.3 %), 4 (81.5 %) and 5 (64.8 %) compared to other clades (collectively 26.9 %) (P<0.0001). MDR prevalence was highest in clade 4 (61.6 %) which was over three times higher than in clade 2, the clade with the second-highest MDR prevalence (18.3 %). There was a strong association between specific AMR determinants and three major epidemic C. difficile STs: ST1 (clade 2) with fluoroquinolone resistance (mainly T82I substitution in GyrA) (P<0.0001), ST11 (clade 5) with tetracycline resistance (various tet-family genes) (P<0.0001) and ST37 (clade 4) with macrolide-lincosamide-streptogramin B (MLSB) resistance (mainly ermB) (P<0.0001) and MDR (P<0.0001). A novel and previously overlooked tetM-positive transposon designated Tn6944 was identified, predominantly among clade 2 strains. This study provides a comprehensive review of AMR in the global C. difficile population which may aid in the early detection of drug-resistant C. difficile strains, and prevention of their dissemination worldwide.

Conserved and specialized functions of Type VII secretion systems in non-tuberculous mycobacteria

Microbiology ◽  
2021 ◽  
Vol 167 (7) ◽  
Author(s):  
Marion Lagune ◽  
Cecile Petit ◽  
Flor Vásquez Sotomayor ◽  
Matt D. Johansen ◽  
Kathrine S. H. Beckham ◽  
...  
Keyword(s):  
Type Species ◽  
Functional System ◽  
Mycobacterium Abscessus ◽  
Individual Species ◽  
Secretion Systems ◽  
Emerging Pathogens ◽  
Content Type ◽  
Link Type ◽  
Type Vii Secretion ◽  
Mycobacterium Xenopi

Non-tuberculous mycobacteria (NTM) are a large group of micro-organisms comprising more than 200 individual species. Most NTM are saprophytic organisms and are found mainly in terrestrial and aquatic environments. In recent years, NTM have been increasingly associated with infections in both immunocompetent and immunocompromised individuals, prompting significant efforts to understand the diverse pathogenic and signalling traits of these emerging pathogens. Since the discovery of Type VII secretion systems (T7SS), there have been significant developments regarding the role of these complex systems in mycobacteria. These specialised systems, also known as Early Antigenic Secretion (ESX) systems, are employed to secrete proteins across the inner membrane. They also play an essential role in virulence, nutrient uptake and conjugation. Our understanding of T7SS in mycobacteria has significantly benefited over the last few years, from the resolution of ESX-3 structure in Mycobacterium smegmatis , to ESX-5 structures in Mycobacterium xenopi and Mycobacterium tuberculosis . In addition, ESX-4, considered until recently as a non-functional system in both pathogenic and non-pathogenic mycobacteria, has been proposed to play an important role in the virulence of Mycobacterium abscessus ; an increasingly recognized opportunistic NTM causing severe lung diseases. These major findings have led to important new insights into the functional mechanisms of these biological systems, their implication in virulence, nutrient acquisitions and cell wall shaping, and will be discussed in this review.

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