Short-Term Pretreatment of Sub-Inhibitory Concentrations of Gentamycin Inhibits the Swarming Motility of Escherichia Coli by Down-Regulating the Succinate Dehydrogenase Gene.
OBJECTIVE
Motility is a feature of many pathogens that contributes to the migration and dispersion of the infectious agent. Whether gentamycin has a post-antibiotic effect (PAE) on the swarming and swimming motility of Escherichia coli (E. coli) remains unknown. In this study, we aimed to examine whether short-term pretreatment of sub-inhibitory concentrations of gentamycin alter motility of E. coli and the mechanisms involved therein.


METHODS
After exposure to sub-inhibitory concentrations (0.8 μg/ml) of gentamicin, the swarming and swimming motility of E. coli was tested in semi-solid media. Real-time PCR was used to detect the gene expression of succinate dehydrogenase (SDH). The production of SDH and fumarate by E. coli pretreated with or without gentamycin was measured. Fumarate was added to swarming agar to determine whether fumarate could restore the swarming motility of E. coli.


RESULTS
After pretreatment of E. coli with sub-inhibitory concentrations of gentamycin, swarming motility was repressed in the absence of growth inhibition. The expression of all four subunits of SDH was down-regulated, and the intracellular concentration of SDH and fumarate, produced by E. coli, were both decreased. Supplementary fumarate could restore the swarming motility inhibited by gentamycin. A selective inhibitor of SDH (propanedioic acid) could strongly repress the swarming motility.


CONCLUSIONS
Sub-inhibitory concentrations of gentamycin inhibits the swarming motility of E. coli. This effect is mediated by a reduction in cellular fumarate caused by down-regulation of SDH. Gentamycin may be advantageous for treatment of E. coli infections.
Department of Pharmacology, Shantou University Medical College, Shantou, China.
Yijing
Y
Zhuang
Weidong
W
Chen
Fen
F
Yao
Yuanchun
Y
Huang
Shuqin
S
Zhou
Haiyan
H
Li
Zijie
Z
Zhang
Congyi
C
Cai
Yi
Y
Gao
Qing
Q
Peng
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D005420:Flavoproteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D005650:Fumarates / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D005839:Gentamicins / Q000494:pharmacology*; D008314:Malonates / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009068:Movement / Q000187:drug effects; D021122:Protein Subunits / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D019802:Succinic Acid / Q000378:metabolism; D013997:Time Factors
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D005420:Flavoproteins; D005650:Fumarates; D005839:Gentamicins; D008314:Malonates; D021122:Protein Subunits; C084271:SdhA protein, Bacteria; C038080:ethylmalonic acid; C032005:fumaric acid; D019802:Succinic Acid