Draft Genome Sequence of Mycobacterium abscessus Bamboo

Yee, Michelle; Klinzing, David C.; Wei, Jun-Rong; Gengenbacher, Martin; Rubín, Eric J.; Dick, Thomas

doi:10.1128/genomea.00388-17

Cited by 34 publications

(45 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We show that Mab Bamboo, a recent clinical isolate we use in our Mab drug discovery projects (Yee et al, 2017), is capable of surviving extended periods of time without oxygen or nutrients by shifting to a non-replicating state. As Mab was shown to grow as biofilms in patients (Qvist et al, 2015;Fennelly et al, 2016), we also developed an in vitro biofilm model for this strain.…”

Section: Discussionmentioning

confidence: 92%

“…The strain was previously wholegenome sequenced which showed that it belongs to M. abscessus subsp. abscessus and harbors an inactive, clarithromycin-sensitive erm(41) C28 sequevar (Yee et al, 2017 Amikacin, imipenem, moxifloxacin and cefoxitin were dissolved in water as recommended by manufacturer and sterilized using 0.2 µm PTFE membrane filters (Acrodisc PALL 4225, Ann Arbor, MI, United States) before use. The N-substituted indolemethylamine IMA6 N-[(6-Trifluoromethyl-1H-indol-2yl)methyl]cyclooctanamine and the N 1 ,N 3 -dialkyl substituted dioxonaphthoimidazolium SA23 1-Butyl-2-methyl-3-octyl-4,9dioxo-4,9-dihydro-1H-naphtho[2,3-d]imidazol-3-ium bromide were synthesized in-house in the context of M. tuberculosis drug discovery projects (Supplementary Figures S1, S2; Dick and Go, unpublished).…”

Section: Methodsmentioning

confidence: 99%

“…Here, we describe the establishment and application of "persister assays" for Mab drug discovery. We chose the strain Mab subspecies abscessus Bamboo (Yee et al, 2017), a recent clinical isolate that our lab uses extensively for screening to identify anti-Mab actives Low et al, 2017). First, we show that Mab Bamboo is capable of surviving oxygen deprivation and nutrient starvation for extended periods of time in a non-replicating state and can grow as a biofilm attached to a surface.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Extreme Drug Tolerance of Mycobacterium abscessus “Persisters”

Yam

Álvarez

et al. 2020

Front. Microbiol.

Self Cite

View full text Add to dashboard Cite

Persistence of infection despite extensive chemotherapy with antibiotics displaying low MICs is a hallmark of lung disease caused by Mycobacterium abscessus (Mab). Thus, the classical MIC assay is a poor predictor of clinical outcome. Discovery of more efficacious antibiotics requires more predictive in vitro potency assays. As a mycobacterium, Mab is an obligate aerobe and a chemo-organo-heterotroph -it requires oxygen and organic carbon sources for growth. However, bacteria growing in patients can encounter micro-environmental conditions that are different from aerated nutrient-rich broth used to grow planktonic cultures for MIC assays. These in vivo conditions may include oxygen and nutrient limitation which should arrest growth. Furthermore, Mab was shown to grow as biofilms in vivo. Here, we show Mab Bamboo, a clinical isolate we use for Mab drug discovery, can survive oxygen deprivation and nutrient starvation for extended periods of time in non-replicating states and developed an in vitro model where the bacterium grows as biofilm. Using these culture models, we show that non-replicating or biofilm-growing bacteria display tolerance to clinically used anti-Mab antibiotics, consistent with the observed persistence of infection in patients. To demonstrate the utility of the developed "persister" assays for drug discovery, we determined the effect of novel agents targeting membrane functions against these physiological forms of the bacterium and find that these compounds show "antipersister" activity. In conclusion, we developed in vitro "persister" assays to fill an assay gap in Mab drug discovery compound progression and to enable identification of novel lead compounds showing "anti-persister" activity.

show abstract

Section: Discussionmentioning

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Extreme Drug Tolerance of Mycobacterium abscessus “Persisters”

Yam

Álvarez

et al. 2020

Front. Microbiol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Whole genome sequencing showed that the strain belongs to M. abscessus subsp. abscessus and harbors an inactive, clarithromycin sensitive, erm (41) C28 sequevar (Yee et al, 2017 ). M. avium 11 was isolated from the bone marrow of a patient with acquired immunodeficiency syndrome with disseminated infection and was provided by Jung-Yien Chien and Po-Ren Hsueh, National Taiwan University Hospital, Taipei.…”

Section: Methodsmentioning

confidence: 99%

Screening of TB Actives for Activity against Nontuberculous Mycobacteria Delivers High Hit Rates

Low

Aziz

et al. 2017

Front. Microbiol.

Self Cite

View full text Add to dashboard Cite

The prevalence of lung disease due to infections with nontuberculous mycobacteria (NTM) has been increasing and surpassed tuberculosis (TB) in some countries. Treatment outcomes are often unsatisfactory, highlighting an urgent need for new anti-NTM medications. Although NTM in general do not respond well to TB specific drugs, the similarities between NTM and Mycobacterium tuberculosis at the molecular and cell structural level suggest that compound libraries active against TB could be leveraged for NTM drug discovery. Here we tested this hypothesis. The Pathogen Box from the Medicines for Malaria Venture (MMV) is a collection of 400 diverse drug-like compounds, among which 129 are known to be active against M. tuberculosis. By screening this compound collection against two NTM species, Mycobacterium abscessus and Mycobacterium avium, we showed that indeed the hit rates for NTM among TB active compounds is significantly higher compared to compounds that are not active against TB. MIC/dose response confirmation identified 10 top hits. Bactericidal activity determination demonstrated attractive potency for a subset of the confirmed hits. In vivo pharmacokinetic profiling showed that some of the compounds present reasonable starting points for medicinal chemistry programs. Three of the top hits were oxazolidinones, suggesting the potential for repositioning this class of protein synthesis inhibitors to replace linezolid which suffers from low potency. Two hits were inhibitors of the trehalose monomycolate transporter MmpL3, suggesting that this transmembrane protein may be an attractive target for NTM. Other hits are predicted to target a range of functions, including cell division (FtsZ), DNA gyrase (GyrB), dihydrofolate reductase, RNA polymerase and ABC transporters. In conclusion, our study showed that screening TB active compounds for activity against NTM resulted in high hit rates, suggesting that this may be an attractive approach to kick start NTM drug discovery projects. In addition, the work identified a series of novel high value NTM hits with associated candidate targets which can be followed up in hit-to-lead projects for the discovery of new NTM antibiotics.

show abstract

“…Genomic DNA of M. avium 11 was extracted from a log-phase liquid culture using the phenol-chloroform method as described previously ( 9 ). The DNA libraries were prepared using Covaris shearing and Illumina TruSeq Nano DNA library preparation kits.…”

Section: Genome Announcementmentioning

confidence: 99%