Using a Chemical Genetic Screen to Enhance Our Understanding of the Antimicrobial Properties of Gallium against Escherichia coli
Abstract
:1. Introduction
2. Materials and Methods
2.1. Escherichia coli Strains
2.2. Determination of the Minimal Inhibitory Concentration and Controls
2.3. Screening
2.4. Normalization
2.5. Data Mining and Analyses
3. Results and Discussion
3.1. Genome-Wide Screen of Ga Resistant and Sensitive Hits
3.2. Ga Sensitive Systems
3.2.1. Iron Homeostasis and Transport, and Fe–Sulfur Cluster Proteins
3.2.2. Oxidative Stress
3.2.3. Deoxynucleotide and Cofactor Biosynthesis, and DNA Replication and Repair
3.3. Systems Involved in Ga Resistance
3.3.1. Fe Transport Systems
3.3.2. Amino Acid Biosynthesis
3.3.3. Lipopolysaccharides and Peptidoglycan
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Appendix A
Systems | Subsystems 1 |
---|---|
Regulation | Signaling, Sigma factor regulon, Transcription factor, and Transcription factor regulons |
Response to stimulus | Starvation, Heat, Cold, DNA damage, pH, Detoxification, Osmotic stress, and Other |
Cellular processes | Cell cycle and division, Cell death, Genetic transfer, Biofilm formation, Quorum sensing, Adhesion, Locomotion, Viral response, Response to bacterium, Host interactions, Symbiosis, and Other proteins |
Energy | Glycolysis, Pentose phosphate pathway, TCA cycle, Fermentation, Aerobic and anaerobic respiration, and Other proteins |
Other pathways | Detoxification, Inorganic nutrient metabolism, Macromolecule modification, Activation/inactivation/interconversion, and Other enzymes |
Degradation | Amino acids, Fatty acid/lipid, Nucleotide/nucleoside, Amine, Carbohydrate/carboxylate, Secondary metabolite, Alcohol, Polymer, Cell exterior and Other proteins |
Biosynthesis | Amino acids, Nucleotide/nucleoside, Fatty acid/lipid, Amines, Carbohydrate/carboxylates, Cofactors, Secondary metabolites, Polymer, and Other proteins |
Cell exterior | Transport, Cell wall biogenesis and organization, Lipopolysaccharide metabolism, Pilus, Flagellar, Outer membrane, Inner membrane, Periplasm, and Cell wall components |
Central dogma | Transcription, Translation, DNA metabolism, RNA metabolism, Protein metabolism, and Protein folding, and secretion |
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System | Subsystem | Gene 1 | Score 2,3 |
---|---|---|---|
Central dogma | Transcription | evgA | −0.166 |
hns | −0.175 | ||
lgoR | −0.401 | ||
nagC | −0.191 | ||
rseA | −0.26 | ||
ulaR | −0.556 | ||
Translation | bipA | −0.204 | |
DNA metabolism | holC | −0.327 | |
holD | −0.217 | ||
ruvC | −0.184 | ||
intR | −0.27 | ||
recA | −0.309 | ||
recD | −0.199 | ||
RNA metabolism | rbfA | −0.35 | |
rim | −0.298 | ||
mnmA | −0.212 | ||
rnt | −0.322 | ||
ygfZ | −0.373 | ||
evgA | −0.166 | ||
hns | −0.175 | ||
lgoR | −0.401 | ||
nagC | −0.191 | ||
rseA | −0.269 | ||
sspA | −0.214 | ||
ulaR | −0.556 | ||
Protein metabolism | lipA | −0.318 | |
pphA | −0.198 | ||
slyD | −0.273 | ||
Protein folding and secretion | slyD | −0.273 | |
Cell exterior | Transport | zunC | −0.361 |
tolC | −0.539 | ||
ugpC | −0.29 | ||
Pilus | ybgO | −0.163 | |
Flagellum | fliG | −0.235 | |
Outer membrane | tolC | −0.539 | |
Plasma membrane | clsA | −0.171 | |
cysQ | −0.203 | ||
fdnI | −0.251 | ||
fliG | −0.235 | ||
gspA | −0.199 | ||
hokA | −0.181 | ||
nuoK | −0.247 | ||
rseA | −0.269 | ||
ubiG | −0.265 | ||
ugpC | −0.29 | ||
znuC | −0.361 | ||
Periplasm | tolC | −0.539 | |
yebF | −0.268 | ||
Biosynthesis | Amino acid | dmI | −0.418 |
metL | −0.189 | ||
mtn | −0.329 | ||
Nucleoside and nucleotide | purT | −0.216 | |
Fatty acid/lipid | clsA | −0.171 | |
Carbohydrate | mdh | −0.287 | |
Secondary metabolites | mtn | −0.329 | |
fdx | −0.168 | ||
Cofactor | fdx | −0.168 | |
gshA | −0.165 | ||
lipA | −0.318 | ||
pabA | −0.224 | ||
pabC | −0.258 | ||
ubiG | −0.265 | ||
Other | metL | −0.189 | |
Degradation | Amino acid | astD | −0.301 |
Nucleoside and nucleotide | mtn | −0.329 | |
Amine | purT | −0.216 | |
Carbohydrate | garK | −0.173 | |
dmlA | −0.418 | ||
Energy | Glycolysis | gpmA | −0.175 |
Tricarboxylic acid cycle | mdh | −0.287 | |
Fermentation | mdh | −0.287 | |
Aerobic respiration | nuoK | −0.247 | |
Anaerobic respiration | fdnI | −0.251 | |
nuoK | −0.247 | ||
Other | mdh | −0.287 | |
nuoK | −0.247 | ||
Cellular processes | Biofilm | hns | −0.175 |
Adhesion | ybgO | −0.163 | |
Locomotion | fliG | −0.235 | |
recA | −0.309 | ||
Viral response | intR | −0.27 | |
Host interaction | intR | −0.27 | |
slyD | −0.273 | ||
Symbiosis | slyD | −0.273 | |
Response to stimulus | Starvation | sspA | −0.29 |
ugpC | −0.214 | ||
Heat | bipA | −0.204 | |
gloB | −0.297 | ||
slyD | −0.273 | ||
Cold | bipA | −0.204 | |
rbfA | −0.35 | ||
DNA damage | rbfA | −0.35 | |
recA | −0.39 | ||
recD | −0.199 | ||
ruvC | −0.184 | ||
Osmotic stress | gshA | −0.165 | |
ubiG | −0.265 | ||
Other | evgA | −0.166 | |
fliG | −0.235 | ||
grxD | −0.266 | ||
holC | −0.327 | ||
holD | −0.217 | ||
pphA | −0.198 | ||
rseA | −0.269 | ||
sspA | −0.214 | ||
tolC | −0.539 | ||
ugpC | −0.29 | ||
Other pathways | Inorganic nutrient metabolism | fdnI | −0.251 |
nuoK | −0.247 | ||
Detoxification | gloB | −0.297 | |
grxD | −0.266 | ||
Macromolecule modification | mnmA | −0.212 | |
rnt | −0.322 | ||
Other enzymes | bfr | −0.17 | |
cysQ | −0.203 | ||
pphA | −0.198 | ||
recD | −0.199 | ||
ruvC | −0.184 | ||
slyD | −0.273 |
System | Subsystem | Gene 1 | Score 2,3 |
---|---|---|---|
Central dogma | Transcription | ilvY | 0.215 |
metR | 0.372 | ||
odhR | 0.353 | ||
DNA metabolism | hofM | 0.62 | |
xerD | 0.168 | ||
cas2 | 0.177 | ||
RNA metabolism | symE | 0.177 | |
ilvY | 0.215 | ||
metR | 0.372 | ||
pdhR | 0.353 | ||
Protein metabolism | mrcB | 0.249 | |
Protein folding and secretion | yraI | 0.18 | |
Cell exterior | Transport | cysU | 0.362 |
fepG | 0.312 | ||
tonB | 0.341 | ||
caiT | 0.403 | ||
yiaO | 0.6 | ||
par | 0.266 | ||
Cell wall biogenesis | alr | 0.353 | |
evnC | 0.203 | ||
mrcB | 0.249 | ||
yraI | 0.18 | ||
Lipopolysaccharide metabolism | cspG | 0.204 | |
rfaC | 0.201 | ||
Outer membrane | par | 0.266 | |
pqiC | 0.345 | ||
Plasma membrane | atpE | 0.172 | |
atpH | 0.176 | ||
caiT | 0.403 | ||
cycU | 0.362 | ||
envU | 0.203 | ||
fepG | 0.312 | ||
mrcB | 0.249 | ||
pqiC | 0.345 | ||
tonB | 0.341 | ||
torC | 0.259 | ||
rfaC | 0.201 | ||
yaaU | 0.237 | ||
yafU | 0.214 | ||
yifK | 0.18 | ||
Periplasm | ansB | 0.204 | |
asr | 0.247 | ||
envC | 0.203 | ||
mrcB | 0.249 | ||
pqiC | 0.345 | ||
tolB | 0.2 | ||
tonB | 0.341 | ||
torC | 0.259 | ||
yiaO | 0.6 | ||
yral | 0.18 | ||
Cell wall component | mrcB | 0.249 | |
torC | 0.259 | ||
Biosynthesis | Amino acid | alr | 0.353 |
avtA | 0.384 | ||
leuA | 0.302 | ||
leuC | 0.205 | ||
metA | 0.241 | ||
proB | 0.258 | ||
trpB | 0.611 | ||
trpD | 0.273 | ||
Fatty acid/lipid | rfaC | 0.201 | |
Carbohydrate | cpsG | 0.204 | |
rfaC | 0.201 | ||
Cofactor, prosthetic groups, electron carrier | bioF | 0.183 | |
bioH | 0.194 | ||
coaA | 0.193 | ||
thiE | 0.226 | ||
Cell structure | mrcB | 0.249 | |
Other | aroF | 0.236 | |
Degradation | Amino acid | alr | 0.353 |
ansB | 0.204 | ||
Fatty acid/lipid | atoA | 0.246 | |
Energy | Glycolysis | pykF | 0.169 |
Fermentation | pykF | 0.169 | |
Anaerobic respiration | torC | 0.259 | |
Adenosine triphosphate biosynthesis | atpE | 0.172 | |
atpH | 0.176 | ||
Other | hydN | 0.249 | |
Cellular processes | Cell cycle/division | envC | 0.203 |
tolB | 0.2 | ||
xerD | 0.168 | ||
Cell death | envC | 0.203 | |
Adhesion | tonB | 0.341 | |
Viral response | cas2 | 0.177 | |
tonB | 0.341 | ||
Symbiosis | tonB | 0.341 | |
Response to stimulus | Heat | pykF | 0.169 |
DNA damage | par | 0.266 | |
symE | 0.177 | ||
yiaO | 0.6 | ||
pH | oxc | 0.519 | |
Other | asr | 0.247 | |
caiT | 0.403 | ||
cas2 | 0.177 | ||
envC | 0.203 | ||
mrcB | 0.249 | ||
tolB | 0.2 | ||
tonB | 0.341 | ||
torC | 0.259 | ||
xerD | 0.168 | ||
yaaU | 0.237 | ||
Other pathways | Other enzymes | oxc | 0.519 |
sepG | 0.201 |
Gene | Score without HA | Score with HA 1,2 |
---|---|---|
ruvA | N/A | −0.257 |
recA | −0.309 | −0.299 |
ruvC | −0.184 | −0.299 |
holC | −0.327 | −0.351 |
recD | −0.199 | −0.561 |
Gene | Score without SMM | Score with SMM 1,2 |
---|---|---|
leuA | 0.302 | 0.341 |
ilvY | 0.215 | 0.3 |
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Share and Cite
Gugala, N.; Chatfield-Reed, K.; Turner, R.J.; Chua, G. Using a Chemical Genetic Screen to Enhance Our Understanding of the Antimicrobial Properties of Gallium against Escherichia coli. Genes 2019, 10, 34. https://doi.org/10.3390/genes10010034
Gugala N, Chatfield-Reed K, Turner RJ, Chua G. Using a Chemical Genetic Screen to Enhance Our Understanding of the Antimicrobial Properties of Gallium against Escherichia coli. Genes. 2019; 10(1):34. https://doi.org/10.3390/genes10010034
Chicago/Turabian StyleGugala, Natalie, Kate Chatfield-Reed, Raymond J. Turner, and Gordon Chua. 2019. "Using a Chemical Genetic Screen to Enhance Our Understanding of the Antimicrobial Properties of Gallium against Escherichia coli" Genes 10, no. 1: 34. https://doi.org/10.3390/genes10010034
APA StyleGugala, N., Chatfield-Reed, K., Turner, R. J., & Chua, G. (2019). Using a Chemical Genetic Screen to Enhance Our Understanding of the Antimicrobial Properties of Gallium against Escherichia coli. Genes, 10(1), 34. https://doi.org/10.3390/genes10010034