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| Status |
Public on Aug 02, 2019 |
| Title |
Genome-wide Assessment of Antimicrobial Tolerance in Yersinia pseudotuberculosis Under Ciprofloxacin Stress |
| Organism |
Yersinia pseudotuberculosis IP 32953 |
| Experiment type |
Other
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| Summary |
Yersinia pseudotuberculosis is a Gram-negative bacterium capable of causing gastrointestinal infection and is closely related to the highly virulent plague bacillus Yersinia pestis. Infection by both species are currently treatable with antibiotics such as ciprofloxacin, a quinolone-class drug of major clinical importance in the treatment of many other infections. Our current understanding of the mechanism of action of ciprofloxacin is that it inhibits DNA replication by targeting DNA gyrase, and that resistance is primarily due to mutation at this target site, along with generic efflux and detoxification strategies. We utilised transposon directed insertion site sequencing (TraDIS or TnSeq) to identify the non-essential chromosomal genes in Y. pseudotuberculosis that are required to tolerate sub-lethal concentrations of ciprofloxacin in vitro. As well as highlighting recognised antibiotic resistance genes, we provide evidence that a multitude of genes involved in regulating DNA replication and repair are central in enabling Y. pseudotuberculosis to tolerate the antibiotic, including dksA (yptb0734), a regulator of RNA polymerase and hda (yptb2792), an inhibitor of DNA replication initiation. We furthermore demonstrate that even at sub-lethal concentrations, ciprofloxacin causes severe cell-wall stress, requiring lipopolysaccharide lipid A, O-antigen and core biosynthesis genes to resist the sub-lethal effects of the antibiotic. It is evident that coping with the consequence(s) of antibiotic-induced stress requires the contribution of scores of genes that are not exclusively engaged in drug-resistance.
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| Overall design |
TnSeq was used to identify the non-essential chromosomal genes in Y. pseudotuberculosis that are required to tolerate sub-lethal concentrations of ciprofloxacin in vitro.
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| Contributor(s) |
Willcocks SJ, Huse KK, Stabler R, Oyston PC, Scott A, Atkins HS, Wren BW |
| Citation(s) |
31580793 |
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| Submission date |
Aug 01, 2019 |
| Last update date |
Dec 31, 2019 |
| Contact name |
Sam Willcocks |
| E-mail(s) |
sam.willcocks@lshtm.ac.uk
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| Organization name |
LSHTM
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| Street address |
Keppel St
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| City |
London |
| ZIP/Postal code |
WC1E7HT |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL27002 |
Illumina MiSeq (Yersinia pseudotuberculosis IP 32953) |
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| Samples (3) |
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| Relations |
| BioProject |
PRJNA558084 |
| SRA |
SRP217195 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE135236_RAW.tar |
1.4 Mb |
(http)(custom) |
TAR (of TXT) |
| GSE135236_sam_all.position.txt.gz |
552.2 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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