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Series GSE99625 Query DataSets for GSE99625
Status Public on Aug 02, 2018
Title Host-directed adjunctive therapy with pravastatin against chronic TB in mice
Organism Mus musculus
Experiment type Expression profiling by array
Summary Mycobacterium tuberculosis (Mtb) is known to subvert immune responses to establish infection and cause disease. Thus, host-directed therapy (HDT), as adjunctive treatment to traditional antitubercular regimens, is an attractive strategy. Statins are a class of drugs used to lower cholesterol levels by inhibiting the 3-hydroxy-3-methylglutaryl coenzyme A reductase, a crucial enzyme in the cholesterol biosynthesis pathway. Here, we conducted a preclinical animal study aimed at comparing the bactericidal activities of the standard TB regimen (rifampin, isoniazid, pyrazinamide and ethambutol; RHZE) with or without escalating doses of pravastatin against chronic TB in BALB/c mice. Antibiotics were given five times weekly for 8 weeks (continuous phase) beginning 6 weeks after infection. Treatment with RHZE plus pravastatin at doses ranging from 30 mg/kg to 180 mg/kg demonstrated a dose-dependent increase in bactericidal activity, reducing lung bacillary counts by 0.2–0.6 log10, 0.3–0.6 log10 and 0.3–0.8 log10 compared to RHZE alone at weeks 2, 4 and 8, respectively. After 8 weeks of treatment, the degree of lung inflammation correlated with the bactericidal activity of each drug regimen.
In order to gain insight into the anti-TB mechanism of action of pravastatin in vivo, the lungs of mice treated with pravastatin adjunctive therapy and those treated with RHZE alone were analyzed by whole-genome microarrays and RT-PCR. Mouse sera were studied by multiplex enzyme-linked immunosorbent assays. Treatment with pravastatin for 1 month had a profound effect on the global transcription in mouse lungs.
 
Overall design Mtb-infected BALB/c mice were treated with the standard TB regimen (RHZE= rifampicin 10 mg/kg+ isoniazid 10 mg/kg + pyrazinamide 150 mg/kg+ ethambutol 100 mg/kg) with or without increasing doses of pravastatin (30, 90, 180 mg/kg). Treatment was given orally five times weekly for 4 weeks (continuous phase) beginning 6 weeks after infection
 
Contributor(s) Dutta NK, Karakousis PC
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Submission date Jun 02, 2017
Last update date Jul 25, 2021
Contact name Noton K Dutta
E-mail(s) notonkumardutta@gmail.com
Organization name Johns Hopkins University
Department Medicine
Lab Center for Tuberculosis Research
Street address 1550 Orleans Street, Room 110
City Baltimore
State/province MD
ZIP/Postal code 21287
Country USA
 
Platforms (1)
GPL11202 Agilent-026655 Whole Mouse Genome Microarray 4x44K v2 (Probe Name version)
Samples (16)
GSM2648888 Infected_untreated_rep1
GSM2648889 Infected_untreated_rep2
GSM2648890 Infected_treated_P30 alone_rep1
Relations
BioProject PRJNA389105

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE99625_RAW.tar 143.4 Mb (http)(custom) TAR (of TXT)
GSE99625_all_data_normalized_in_GeneSpring.txt.gz 4.1 Mb (ftp)(http) TXT
Processed data included within Sample table
Processed data are available on Series record

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