Journal: Microbiology Spectrum

Article Title: In Vitro Profiling of the Synthetic RNA Polymerase Inhibitor MMV688845 against Mycobacterium abscessus

doi: 10.1128/spectrum.02760-22

Figure Lengend Snippet: In vitro activity of MMV688845 against M. abscessus reference strains and clinical isolates

Article Snippet: To study the synergy of MMV688845 with approved antimycobacterial drugs and to assess its suitability for combination therapy, we performed synergy testing against M. abscessus (ATCC 19977) by checkerboard assays.

Techniques: In Vitro, Activity Assay, Infection

Journal: Microbiology Spectrum

Article Title: In Vitro Profiling of the Synthetic RNA Polymerase Inhibitor MMV688845 against Mycobacterium abscessus

doi: 10.1128/spectrum.02760-22

Figure Lengend Snippet: MICs and MBCs of MMV688845 and rifabutin against M. abscessus subsp. abscessus ATCC 19977

Article Snippet: To study the synergy of MMV688845 with approved antimycobacterial drugs and to assess its suitability for combination therapy, we performed synergy testing against M. abscessus (ATCC 19977) by checkerboard assays.

Techniques: Infection

Journal: Microbiology Spectrum

Article Title: In Vitro Profiling of the Synthetic RNA Polymerase Inhibitor MMV688845 against Mycobacterium abscessus

doi: 10.1128/spectrum.02760-22

Figure Lengend Snippet: Bactericidal activity of MMV688845 and rifabutin against M. abscessus ATCC 19977. LOD, limit of detection. Experiments were carried out in duplicate or triplicate. Results are means, with the standard deviations displayed as error bars. A one-way analysis of variance (ANOVA) multiple-comparison test was performed using GraphPad Prism 8 software to compare treated groups with the DMSO control. ****, P ≤ 0.0001.

Article Snippet: To study the synergy of MMV688845 with approved antimycobacterial drugs and to assess its suitability for combination therapy, we performed synergy testing against M. abscessus (ATCC 19977) by checkerboard assays.

Techniques: Activity Assay, Comparison, Software, Control

Journal: Microbiology Spectrum

Article Title: In Vitro Profiling of the Synthetic RNA Polymerase Inhibitor MMV688845 against Mycobacterium abscessus

doi: 10.1128/spectrum.02760-22

Figure Lengend Snippet: Characterization of M. abscessus MMV688845-resistant mutants

Article Snippet: To study the synergy of MMV688845 with approved antimycobacterial drugs and to assess its suitability for combination therapy, we performed synergy testing against M. abscessus (ATCC 19977) by checkerboard assays.

Techniques: Mutagenesis

Journal: Microbiology Spectrum

Article Title: In Vitro Profiling of the Synthetic RNA Polymerase Inhibitor MMV688845 against Mycobacterium abscessus

doi: 10.1128/spectrum.02760-22

Figure Lengend Snippet: Visualization of RpoB mutations in an M. abscessus homology model. Beige, M. tuberculosis RpoB [PDB 5UHE ] with d-AAP 1 bound; light blue, M. abscessus homology model built using RoseTTAfold; red, M. abscessus resistance mutations; green, H bonds. ( , ).

Article Snippet: To study the synergy of MMV688845 with approved antimycobacterial drugs and to assess its suitability for combination therapy, we performed synergy testing against M. abscessus (ATCC 19977) by checkerboard assays.

Techniques:

Journal: Microbiology Spectrum

Article Title: In Vitro Profiling of the Synthetic RNA Polymerase Inhibitor MMV688845 against Mycobacterium abscessus

doi: 10.1128/spectrum.02760-22

Figure Lengend Snippet: In vitro activity of antibiotics against M. abscessus ATCC 19977

Article Snippet: To study the synergy of MMV688845 with approved antimycobacterial drugs and to assess its suitability for combination therapy, we performed synergy testing against M. abscessus (ATCC 19977) by checkerboard assays.

Techniques: In Vitro, Activity Assay

Journal: Microbiology Spectrum

Article Title: In Vitro Profiling of the Synthetic RNA Polymerase Inhibitor MMV688845 against Mycobacterium abscessus

doi: 10.1128/spectrum.02760-22

Figure Lengend Snippet: FICI values for combinations of MMV688845 with antimycobacterial drugs against M. abscessus ATCC 19977 ^a

Article Snippet: To study the synergy of MMV688845 with approved antimycobacterial drugs and to assess its suitability for combination therapy, we performed synergy testing against M. abscessus (ATCC 19977) by checkerboard assays.

Techniques:

Journal: Microbiology Spectrum

Article Title: In Vitro Profiling of the Synthetic RNA Polymerase Inhibitor MMV688845 against Mycobacterium abscessus

doi: 10.1128/spectrum.02760-22

Figure Lengend Snippet: Intracellular synergy of MMV688845 and clarithromycin (CLR). (A to C) Results of the macrophage infection assay with 1.5 μM bedaquiline (BDQ) (A), 3.1 μM CLR plus 1.6 μM MMV688845 (B), or 1% DMSO (C). Pictures were taken with a Cytation 5 imaging reader fluorescence microscope (BioTek). THP-1 macrophages are shown in blue, and M. abscessus (pTEC27) cells are in red. (D to F) growth inhibition of intracellular M. abscessus in the presence of 1.6 μM MMV688845 plus CLR (D), MMV688845 (E), or CLR. Experiments were carried out in duplicate, and the results presented are means, with the standard deviations displayed as error bars.

Article Snippet: To study the synergy of MMV688845 with approved antimycobacterial drugs and to assess its suitability for combination therapy, we performed synergy testing against M. abscessus (ATCC 19977) by checkerboard assays.

Techniques: Infection, Imaging, Fluorescence, Microscopy, Inhibition

Journal: Microbiology Spectrum

Article Title: In Vitro Profiling of the Synthetic RNA Polymerase Inhibitor MMV688845 against Mycobacterium abscessus

doi: 10.1128/spectrum.02760-22

Figure Lengend Snippet: Plasma concentration-time profile of MMV688845 following a single oral dose of 25 mg/kg in CD-1 mice. The MIC of MMV688845 against M. abscessus K21 ( Table 1 ) is indicated by a dotted line. Experiments were carried out in duplicate, and the results presented are as means, with the standard deviations displayed as error bars.

Article Snippet: To study the synergy of MMV688845 with approved antimycobacterial drugs and to assess its suitability for combination therapy, we performed synergy testing against M. abscessus (ATCC 19977) by checkerboard assays.

Techniques: Clinical Proteomics, Concentration Assay

Journal: Communications Biology

Article Title: Development of a penem antibiotic against Mycobacteroides abscessus

doi: 10.1038/s42003-020-01475-2

Figure Lengend Snippet: a Structures of the carbapenem Imipenem and the penem Faropenem are shown with red arrows indicating the differences in the ring structures. b Structure of the new penem developed here, T405.

Article Snippet: Next, we determined the MIC of T405 against M. abscessus reference strain ATCC 19977, and found it to be 2 μg/mL.

Techniques:

Journal: Communications Biology

Article Title: Development of a penem antibiotic against Mycobacteroides abscessus

doi: 10.1038/s42003-020-01475-2

Figure Lengend Snippet: MICs of T405, imipenem and faropenem tested against the reference strain (ATCC 19977) and 20 clinical strains of M. abscessus in vitro.

Article Snippet: Next, we determined the MIC of T405 against M. abscessus reference strain ATCC 19977, and found it to be 2 μg/mL.

Techniques:

Journal: Communications Biology

Article Title: Development of a penem antibiotic against Mycobacteroides abscessus

doi: 10.1038/s42003-020-01475-2

Figure Lengend Snippet: Frequency of spontaneous resistant mutants of M. abscessus ATCC 19977 recovered against T405 and imipenem at their individual MICs and when the T405 MIC is combined with avibactam at its individual MIC.

Article Snippet: Next, we determined the MIC of T405 against M. abscessus reference strain ATCC 19977, and found it to be 2 μg/mL.

Techniques:

Journal: Communications Biology

Article Title: Development of a penem antibiotic against Mycobacteroides abscessus

doi: 10.1038/s42003-020-01475-2

Figure Lengend Snippet: a Escalating doses of T405 administered alone. b 450 mg/kg dose of T405 administered alone and in combination with probenecid. c Single-dose plasma PK parameters for total T405 concentration in mice after subcutaneous injection of 25 mg/kg ( n = 3 mice per time point per arm).

Article Snippet: Next, we determined the MIC of T405 against M. abscessus reference strain ATCC 19977, and found it to be 2 μg/mL.

Techniques: Clinical Proteomics, Concentration Assay, Injection

Journal: PLOS One

Article Title: A novel variant in MYBPC3 causes hypertrophic cardiomyopathy by haploinsufficiency

doi: 10.1371/journal.pone.0333096

Figure Lengend Snippet: The studied variant is indicated in the representation. cMyBP-C is composed of 11 domains, numbered C0 to C10 from the N-terminus to C-terminus. It includes 8 immunoglobulin (IgI) domains (circles) and 3 fibronectin type III (FnIII) domains (rectangles). Four specific phosphorylation sites are located between C1 and C2, known as MyBP-C motif. The regions of interaction with other sarcomeric proteins (actin, myosin, and titin) are shown with dotted arrows. The relationship between the 35 exons of MYBPC3 cDNA and cMyBP-C domains is indicated by dashed lines.

Article Snippet: The membranes were then incubated with primary antibodies against MYBPC3 (Cat No.19977-1-AP, Proteintech) and tubulin (Cat No.11224-1-AP, Proteintech) at 4°C overnight.

Techniques: Variant Assay, Phospho-proteomics

Journal: PLOS One

Article Title: A novel variant in MYBPC3 causes hypertrophic cardiomyopathy by haploinsufficiency

doi: 10.1371/journal.pone.0333096

Figure Lengend Snippet: (A) RT-qPCR analysis showing significantly decreased MYBPC3 mRNA levels in cardiac sample from the proband compared to control subjects. (B) Representative Western blot images demonstrating reduced cMyBP-C protein expression in the HCM heart relative to controls. (C) Semi-quantification of cMyBP-C protein levels normalized to tubulin. Data are presented as mean ± standard deviation (SD); * P < 0.05 versus controls. HCM = hypertrophic cardiomyopathy.

Article Snippet: The membranes were then incubated with primary antibodies against MYBPC3 (Cat No.19977-1-AP, Proteintech) and tubulin (Cat No.11224-1-AP, Proteintech) at 4°C overnight.

Techniques: Quantitative RT-PCR, Control, Western Blot, Expressing, Standard Deviation