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.

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 Genome Sequence of Mycobacterium abscessus Phage phiT46-1

2021 ◽  
Vol 10 (2) ◽  
Author(s):  
Elizabeth D. Amarh ◽  
Rebekah M. Dedrick ◽  
Rebecca A. Garlena ◽  
Daniel A. Russell ◽  
Deborah Jacobs-Sera ◽  
...  
Keyword(s):  
Genome Sequence ◽  
Mycobacterium Abscessus ◽  
Spontaneous Release ◽  
Secretion Systems ◽  
Content Type ◽  
Type Vii Secretion

ABSTRACT Mycobacteriophage phiT46-1 is a newly isolated Mycobacterium phage that was isolated by spontaneous release from Mycobacterium abscessus strain Taiwan-46 and infects M. abscessus strain BWH-C. Phage phiT46-1 is unrelated to previously described mycobacteriophages, has a 52,849-bp genome, and includes a polymorphic toxin-immunity cassette associated with type VII secretion systems.

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.

scholarly journals Genome Sequence of Mycobacterium abscessus Phage phiT45-1

2021 ◽  
Vol 10 (10) ◽  
Author(s):  
Elizabeth D. Amarh ◽  
Christian H. Gauthier ◽  
Rebekah M. Dedrick ◽  
Rebecca A. Garlena ◽  
Daniel A. Russell ◽  
...  
Keyword(s):  
Genome Sequence ◽  
Mycobacterium Smegmatis ◽  
Mycobacterium Abscessus ◽  
Secretion Systems ◽  
Content Type ◽  
Type Vii Secretion

ABSTRACT Mycobacteriophage phiT45-1 is a newly isolated bacteriophage spontaneously released from Mycobacterium abscessus strain Taiwan-45 that lytically infects M. abscessus strain BWH-C; phiT45-1 also infects M. abscessus ATCC 19977 but not Mycobacterium smegmatis. Phage phiT45-1 has a 43,407-bp genome and carries a polymorphic toxin-immunity cassette associated with type VII secretion systems.

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 The Prophage and Plasmid Mobilome as a Likely Driver of Mycobacterium abscessus Diversity

mBio ◽  
2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Rebekah M. Dedrick ◽  
Haley G. Aull ◽  
Deborah Jacobs-Sera ◽  
Rebecca A. Garlena ◽  
Daniel A. Russell ◽  
...  
Keyword(s):  
Mycobacterium Abscessus ◽  
Genomic Variation ◽  
Host Cells ◽  
Clinical Isolates ◽  
Genetic Constitution ◽  
Secretion Systems ◽  
Emerging Pathogen ◽  
Content Type ◽  
Type Vii Secretion

ABSTRACT Mycobacterium abscessus is an emerging pathogen that is often refractory to antibiotic control. Treatment is further complicated by considerable variation among clinical isolates in both their genetic constitution and their clinical manifestations. Here, we show that the prophage and plasmid mobilome is a likely contributor to this variation. Prophages and plasmids are common, abundant, and highly diverse, and code for large repertoires of genes influencing virulence, antibiotic susceptibility, and defense against viral infection. At least 85% of the strains we describe carry one or more prophages, representing at least 17 distinct and diverse sequence “clusters,” integrated at 18 different attB locations. The prophages code for 19 distinct configurations of polymorphic toxin and toxin-immunity systems, each with WXG-100 motifs for export through type VII secretion systems. These are located adjacent to attachment junctions, are lysogenically expressed, and are implicated in promoting growth in infected host cells. Although the plethora of prophages and plasmids confounds the understanding of M. abscessus pathogenicity, they also provide an abundance of tools for M. abscessus engineering. IMPORTANCE Mycobacterium abscessus is an important emerging pathogen that is challenging to treat with current antibiotic regimens. There is substantial genomic variation in M. abscessus clinical isolates, but little is known about how this influences pathogenicity and in vivo growth. Much of the genomic variation is likely due to the large and varied mobilome, especially a large and diverse array of prophages and plasmids. The prophages are unrelated to previously characterized phages of mycobacteria and code for a diverse array of genes implicated in both viral defense and in vivo growth. Prophage-encoded polymorphic toxin proteins secreted via the type VII secretion system are common and highly varied and likely contribute to strain-specific pathogenesis.

scholarly journals Bartonella kosoyi sp. nov. and Bartonella krasnovii sp. nov., two novel species closely related to the zoonotic Bartonella elizabethae, isolated from black rats and wild desert rodent-fleas

2020 ◽  
Vol 70 (3) ◽  
pp. 1656-1665 ◽  
Author(s):  
Ricardo Gutiérrez ◽  
Tali Shalit ◽  
Barak Markus ◽  
Congli Yuan ◽  
Yaarit Nachum-Biala ◽  
...  
Keyword(s):  
Type Species ◽  
Rattus Rattus ◽  
Phenotypic Characterization ◽  
Individual Species ◽  
Wild Rodents ◽  
Single Chromosome ◽  
Content Type ◽  
Phenotypic Differences ◽  
Tel Aviv ◽  
Link Type

The genus Bartonella (Family: Bartonellaceae ; Order: Rhizobiales; Class: Alphaproteobacteria) comprises facultative intracellular Gram-negative, haemotropic, slow-growing, vector-borne bacteria. Wild rodents and their fleas harbor a great diversity of species and strains of the genus Bartonella , including several zoonotic ones. This genetic diversity coupled with a fastidious nature of the organism results in a taxonomic challenge that has led to a massive collection of uncharacterized strains. Here, we report the genomic and phenotypic characterization of two strains, members of the genus Bartonella (namely Tel Aviv and OE 1–1), isolated from Rattus rattus rats and Synosternus cleopatrae fleas, respectively. Scanning electron microscopy revealed rod-shaped bacteria with polar pili, lengths ranging from 1.0 to 2.0 µm and widths ranging from 0.3 to 0.6 µm. OE 1–1 and Tel Aviv strains contained one single chromosome of 2.16 and 2.23 Mbp and one plasmid of 29.0 and 41.5 Kbp, with average DNA G+C contents of 38.16 and 38.47 mol%, respectively. These strains presented an average nucleotide identity (ANI) of 89.9 %. Bartonella elizabethae was found to be the closest phylogenetic relative of both strains (ANI=90.9–93.6 %). The major fatty acids identified in both strains were C18:1ω7c, C18 : 0 and C16 : 0. They differ from B. elizabethae in their C17 : 0 and C15 : 0 compositions. Both strains are strictly capnophilic and their biochemical profiles resembled those of species of the genus Bartonella with validly published names, whereas differences in arylamidase activities partially assisted in their speciation. Genomic and phenotypic differences demonstrate that OE 1–1 and Tel Aviv strains represent novel individual species, closely related to B. elizabethae , for which we propose the names Bartonella kosoyi sp. nov. and Bartonella krasnovii sp. nov.

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