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Series GSE275261 Query DataSets for GSE275261
Status Public on Aug 25, 2024
Title Differential effects of inosine monophosphate dehydrogenase (IMPDH/GuaB) inhibition in Acinetobacter baumannii and Escherichia coli
Organisms Acinetobacter baumannii; Escherichia coli
Experiment type Expression profiling by high throughput sequencing
Summary Inosine 5’-monophosphate dehydrogenase (IMPDH) catalyzes the rate-limiting step in the de novo guanine biosynthesis and is conserved from humans to bacteria, where it is called GuaB. We developed a series of potent inhibitors that selectively target GuaB over its human homolog. Here we show that these GuaB inhibitors are bactericidal, generate phenotypic signatures that are distinct from other antibiotics, and elicit different time-kill kinetics and regulatory responses in two important gram-negative pathogens: Acinetobacter baumannii and Escherichia coli. Specifically, the GuaB inhibitor G6 rapidly kills A. baumannii but only kills E. coli after 24 hours. After exposure to G6, the expression of genes involved in purine biosynthesis and stress responses change in opposite directions while siderophore biosynthesis is downregulated in both species. Our results suggest that different species respond to GuaB inhibition using distinct regulatory programs, and possibly explain the different bactericidal kinetics upon GuaB inhibition. The comparison highlights opportunities for developing GuaB inhibitors as novel antibiotics.
 
Overall design In this study, we examined the transcriptional responses to GuaB-specific inhibitors in A. baumannii and E. coli.
 
Contributor(s) Peng Y, Skippington E
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Submission date Aug 20, 2024
Last update date Aug 25, 2024
Contact name Yutian Peng
Organization name Genentech Inc.
Street address 340 Point San Bruno
City South San Francisco
State/province CA
ZIP/Postal code 94080
Country USA
 
Platforms (2)
GPL21433 Illumina HiSeq 4000 (Escherichia coli)
GPL22143 Illumina HiSeq 4000 (Acinetobacter baumannii)
Samples (24)
GSM8473777 ID12167959, Ecoli, No Drug, 0h
GSM8473778 ID12167960, Ecoli, No Drug, 0h
GSM8473779 ID12167961, Ecoli, No Drug, 0h
Relations
BioProject PRJNA1150140

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
GSE275261_Abaumannii_counts.txt.gz 97.5 Kb (ftp)(http) TXT
GSE275261_Abaumannii_metadata_genes.txt.gz 58.4 Kb (ftp)(http) TXT
GSE275261_Abaumannii_metadata_samples.txt.gz 159 b (ftp)(http) TXT
GSE275261_Ecoli_counts.txt.gz 109.4 Kb (ftp)(http) TXT
GSE275261_Ecoli_metadata_genes.txt.gz 84.7 Kb (ftp)(http) TXT
GSE275261_Ecoli_metadata_samples.txt.gz 155 b (ftp)(http) TXT
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