U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

SRX21456040: GSM7729817: BACI355, Suceptable, Time 60 minutes, Replicate B; Bacillus anthracis; RNA-Seq
1 ILLUMINA (Illumina MiSeq) run: 6.5M spots, 974.6M bases, 422.9Mb downloads

External Id: GSM7729817_r1
Submitted by: USAMRIID
Study: Relative quantification of the recA gene for antibiotic susceptibility testing in response to ciprofloxacin for pathogens of concern
show Abstracthide Abstract
Antibiotic resistance (AR) is one of the greatest threats to global health and is associated with higher treatment costs, longer hospital stays, and increased mortality. Current gold standard antibiotic susceptibility tests (AST) are dependent on organism growth rates resulting in prolonged diagnostic answers for slow growing organisms. Changes in the cellular transcriptome can be instantaneous in the presence of stressors such as antibiotic pressure. Here, we demonstrate that relative quantification of the recA gene in response to breakpoint concentrations of ciprofloxacin is an indicator of pathogen susceptibly. For this purpose, we developed seven duplex RT-qPCR assays targeting the recA and 16S rRNA gene, as response and housekeeping genes respectively, for biothreat and ESKAPE pathogens. Surrogate biothreat agents Y. pestis and B. anthracis saw increases in relative recA gene expression, independent of growth rate after 15 minutes of exposure to ciprofloxacin with maximal expression seen after 60 minutes. Treatment with doxycycline also demonstrated an increase in relative recA fold changes compared to no treatment controls. Final evaluation of all seven duplex assays tested across 125 strains, including Tier 1 pathogens, from broth culture demonstrated an overall categorical agreement compared to gold standard microbroth dilution of 97.56% with major error (ME) rates of 1.59% and very major error (VME) rates of 3.23%. Testing on pathogen strains commonly associated with urinary tract infections in contrived clinical sample sets demonstrated an overall categorical agreement of 95.8% with a ME rate of 0.0% and VME rate of 7.69%. These data indicate that relative quantification of a single highly conserved gene accurately predicts susceptibility for multiple bacterial species in response to ciprofloxacin. Overall design: RNA sequencing was performed on bacterial samples exposed to breakpoint concentrations of ciprofloxacin across time. RNA sequencing analysis was compared between resistant and suceptable strains as well as compared across multple organisms including B. anthracis and Y. pestis.
Sample: BACI355, Suceptable, Time 60 minutes, Replicate B
SAMN37115178 • SRS18691949 • All experiments • All runs
Library:
Name: GSM7729817
Instrument: Illumina MiSeq
Strategy: RNA-Seq
Source: TRANSCRIPTOMIC
Selection: cDNA
Layout: PAIRED
Construction protocol: 2 volumes of RNAprotect Bacteria Reagent was added to each tube and incubated at room temperature for 5 minutes at indicated time points. For all reactions tubes were centrifuged at 5000 x g for 10 minutes. The supernatant was decanted, and pellets were extracted or stored at -80°C until processing. Pellets were resuspended in 100µl 1xTE containing 15 mg/ml lysozyme and 10 µl Proteinase K. Suspended pellets were incubated at room temperature for 10 minutes. Then, 700 µl of buffer RLT was added to suspended pellets along with approximately 100 µl of 0.5 mM glass beads and cells were incubated at 95°C for 5 minutes, bead beaten for 10 minutes, then centrifuged at max speed for 30 seconds. 760 µl of supernatant was added to new 2 ml Eppendorf tubes containing 590 µl of 80% ethanol. Samples were then extracted utilizing the RNeasy kit protocol and an on-column DNase treatment according to manufacturer's protocols Extracted RNA was quantified using the Qubit 2.0 Fluorometer and Qubit RNA HS assay. RNA was spiked with the ERCC control, an external RNA control, and input into the QIAseq FastSelect – 5s/16s/23s kit to remove bacterial ribosomal RNA prior to sequencing. Sequencing libraries were prepared using the QIAseq Stranded total RNA library kit according to manufacturer's instructions. Libraries were quantified using the High Sensitivity D1000 kit on the 4200 Tapestation System. Four barcoded libraries were combined and diluted to a 4 nM library pool, denatured with NaOH, and further diluted to a final library concentration of 12 pM prior to sequencing. Pooled libraries were sequenced using the MiSeq Instrument and MiSeq reagent kit version 3–150 cycles.
Runs: 1 run, 6.5M spots, 974.6M bases, 422.9Mb
Run# of Spots# of BasesSizePublished
SRR257324516,480,222974.6M422.9Mb2024-02-07

ID:
28896956

Supplemental Content

Search details

See more...

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...