Using a Chemical Genetic Screen to Enhance Our Understanding of the Antimicrobial Properties of Gallium against Escherichia coli.
Natalie GugalaKate Chatfield-ReedRaymond Joseph TurnerGordon ChuaPublished in: Genes (2019)
The diagnostic and therapeutic agent gallium offers multiple clinical and commercial uses including the treatment of cancer and the localization of tumors, among others. Further, this metal has been proven to be an effective antimicrobial agent against a number of microbes. Despite the latter, the fundamental mechanisms of gallium action have yet to be fully identified and understood. To further the development of this antimicrobial, it is imperative that we understand the mechanisms by which gallium interacts with cells. As a result, we screened the Escherichia coli Keio mutant collection as a means of identifying the genes that are implicated in prolonged gallium toxicity or resistance and mapped their biological processes to their respective cellular system. We discovered that the deletion of genes functioning in response to oxidative stress, DNA or iron⁻sulfur cluster repair, and nucleotide biosynthesis were sensitive to gallium, while Ga resistance comprised of genes involved in iron/siderophore import, amino acid biosynthesis and cell envelope maintenance. Altogether, our explanations of these findings offer further insight into the mechanisms of gallium toxicity and resistance in E. coli.
Keyphrases
- escherichia coli
- oxidative stress
- staphylococcus aureus
- induced apoptosis
- genome wide
- amino acid
- single cell
- high throughput
- dna damage
- papillary thyroid
- biofilm formation
- pet ct
- circulating tumor
- bone marrow
- ischemia reperfusion injury
- diabetic rats
- endoplasmic reticulum stress
- signaling pathway
- smoking cessation
- cell wall
- single molecule
- pseudomonas aeruginosa
- cell free
- circulating tumor cells
- heat stress
- nucleic acid
- transition metal
- heat shock protein