Short-term adaptive metabolic response of Escherichia coli to ciprofloxacin exposure

Year 2021, Volume: 51 Issue: 1, 79 - 84, 30.04.2021

Engin Koçak Ceren Özkul

Abstract

Background and Aims: Antibiotic resistance is one of the most critical global health problems. Understanding the pathogen-antibiotic relationship at molecular level could lead to the discovery of new routes to overcome antibiotic resistance. In our present work, we evaluated early responses of E. coli against ciprofloxacin within 30 min by analyzing metabolome structure. Our main goal was to understand the initial steps of the adaptation and resistance process of pathogens under antibiotic stress. Methods: Metabolomics analysis was performed by processing GC/MS and followed with the MS-DIAL metabolomics platform. In addition, Metaboanalyst 4.0 and the KEGG database were used for statistical and pathway analysis. Results: In total, 207 metabolites were identified while 47 metabolites were significantly different under ciprofloxacin stress condition. Pathway analysis showed that amino acid, fatty acid, and aminoacyl-tRNA metabolisms were altered as an effect of ciprofloxacin at 30 min. Conclusion: Our results suggest that the understanding of bacterial metabolism in early phase bacterial responses to antibiotics could be key to reducing the adaptation and resistance process.

Keywords

Metabolomics, GC/MS, ciprofloxacin, E. coli

References

• • Cameron, J. C., & Pakrasi, H. B. (2010). Essential role of glutathione in acclimation to environmental and redox perturbations in the cyanobacterium Synechocystis sp. PCC 6803. Plant Physiology, 154(4), 1672–1685. doi:10.1104/pp.110.162990
• • Cameron, J. C., & Pakrasi, H. B. (2011). Glutathione facilitates antibiotic resistance and photosystem I stability during exposure to gentamicin in cyanobacteria. Applied and environmental microbiology, 77(10), 3547–3550. doi:10.1128/AEM.02542-10
• • Cheng, Z. X., Guo, C., Chen, Z. G., Yang, T. C., Zhang, J. Y., Wang, J., Peng, X. X. (2019). Glycine, serine and threonine metabolism confounds efficacy of complement-mediated killing. Nature Communications, 10(1), 3325. doi:10.1038/s41467-019-11129-5
• • Chong, J., Soufan, O., Li, C., Caraus, I., Li, S., Bourque, G., Xia, J. (2018). MetaboAnalyst 4.0: towards more transparent and integrative metabolomics analysis. Nucleic Acids Research, 46(W1), W486–W494. doi:10.1093/nar/gky310
• • CLSI. (2015). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard -Tenth Edition.CLSI document M07-A10. In: Wayne, PA: Clinical and Laboratory Standards Institute.
• • Dorries, K., Schlueter, R., & Lalk, M. (2014). Impact of antibiotics with various target sites on the metabolome of Staphylococcus aureus. Antimicrobial Agents and Chemotherapy, 58(12), 7151– 7163. doi:10.1128/AAC.03104-14
• • Dunnick, J. K., & O’Leary, W. M. (1970). Correlation of bacteria lipid composition with antibiotic resistance. Journal of Bacteriol, 101(3), 892–900.
• • Erickson, K. E., Otoupal, P. B., & Chatterjee, A. (2017). Transcriptome- Level Signatures in Gene Expression and Gene Expression Variability during Bacterial Adaptive Evolution. mSphere, 2(1). doi: 10.1128/mSphere.00009-17
• • Gonulalan, E. M., Nemutlu, E., Bayazeid, O., Kocak, E., Yalcin, F. N., & Demirezer, L. O. (2019). Metabolomics and proteomics profiles of some medicinal plants and correlation with BDNF activity. Phytomedicine, 152920. doi:10.1016/j.phymed.2019.152920
• • Hooper, D. C., & Jacoby, G. A. (2015). Mechanisms of drug resistance: quinolone resistance. Annals of New York Academy of Sciences, 1354, 12–31. doi:10.1111/nyas.12830
• • Iravani, A., Tice, A. D., McCarty, J., Sikes, D. H., Nolen, T., Gallis, H. A. et al. (1995). Short-course ciprofloxacin treatment of acute uncomplicated urinary tract infection in women. The minimum effective dose. The Urinary Tract Infection Study Group [corrected]. Archives of Internal Medicine, 155(5), 485–494.
• • Kim, S., Lee, S. W., Choi, E. C., & Choi, S. Y. (2003). Aminoacyl-tRNA synthetases and their inhibitors as a novel family of antibiotics. Applied Microbiol and Biotechnology, 61(4), 278–288. doi:10.1007/ s00253-003-1243-5
• • Lai, Z., Tsugawa, H., Wohlgemuth, G., Mehta, S., Mueller, M., Zheng, Y., Fiehn, O. (2018). Identifying metabolites by integrating metabolome databases with mass spectrometry cheminformatics. Nature Methods, 15(1), 53–56. doi:10.1038/nmeth.4512
• • Lata, M., Sharma, D., Deo, N., Tiwari, P. K., Bisht, D., & Venkatesan, K. (2015). Proteomic analysis of ofloxacin-mono resistant Mycobacterium tuberculosis isolates. Journal of Proteomics, 127(Pt A), 114–121. doi:10.1016/j.jprot.2015.07.031
• • Li, W., Zhang, S., Wang, X., Yu, J., Li, Z., Lin, W., & Lin, X. (2018). Systematically integrated metabonomic-proteomic studies of Escherichia coli under ciprofloxacin stress. Journal of Proteomics, 179, 61–70. doi:10.1016/j.jprot.2018.03.002
• • Machuca, J., Recacha, E., Briales, A., Diaz-de-Alba, P., Blazquez, J., Pascual, A., & Rodriguez-Martinez, J. M. (2017). Cellular Response to Ciprofloxacin in Low-Level Quinolone-Resistant Escherichia coli. Frontiers Microbiology, 8, 1370. doi:10.3389/fmicb.2017.01370
• • Maifiah, M. H., Creek, D. J., Nation, R. L., Forrest, A., Tsuji, B. T., Velkov, T., & Li, J. (2017). Untargeted metabolomics analysis reveals key pathways responsible for the synergistic killing of colistin and doripenem combination against Acinetobacter baumannii. Scientific Reports, 7, 45527. doi:10.1038/srep45527
• • Mills, S. D. (2006). When will the genomics investment pay off for antibacterial discovery? Biochemical Pharmacology, 71(7), 1096– 1102. doi: 10.1016/j.bcp.2005.11.025
• • Moloney, M. G. (2016). Natural Products as a Source for Novel Antibiotics. Trends in Pharmacological Sciences, 37(8), 689–701. doi: 10.1016/j.tips.2016.05.001
• • Piddock, L. J. (1998). Fluoroquinolone resistance: overuse of fluoroquinolones in human and veterinary medicine can breed resistance. British Medicinal Journal, 317(7165), 1029–1030. doi: 10.1136/bmj.317.7165.1029
• • Pulido, M. R., Garcia-Quintanilla, M., Gil-Marques, M. L., & McConnell, M. J. (2016). Identifying targets for antibiotic development using omics technologies. Drug Discovery Today, 21(3), 465–472. doi: 10.1016/j.drudis.2015.11.014
• • Smirnova, G. V., & Oktyabrsky, O. N. (2005). Glutathione in bacteria. Biochemistry (Moscow), 70(11), 1199–1211. doi:10.1007/s10541- 005-0248-3
• • Talan, D. A., Klimberg, I. W., Nicolle, L. E., Song, J., Kowalsky, S. F., & Church, D. A. (2004). Once daily, extended release ciprofloxacin for complicated urinary tract infections and acute uncomplicated pyelonephritis. Journal of Urology, 171(2 Pt 1), 734–739. doi:10.1097/01.ju.0000106191.11936.64
• • Talan, D. A., Naber, K. G., Palou, J., & Elkharrat, D. (2004). Extendedrelease ciprofloxacin (Cipro XR) for treatment of urinary tract infections. International Journal of Antimicrobial Agents, 23 Suppl 1, S54–66. doi:10.1016/j.ijantimicag.2003.12.005
• • Ventola, C. L. (2015). The antibiotic resistance crisis: part 1: causes and threats. P T, 40(4), 277–283.
• • Vranakis, I., Goniotakis, I., Psaroulaki, A., Sandalakis, V., Tselentis, Y., Gevaert, K., & Tsiotis, G. (2014). Proteome studies of bacterial antibiotic resistance mechanisms. Journal of Proteomics, 97, 88–99. doi:10.1016/j.jprot.2013.10.027
• • Yano, Y., Nakayama, A., Ishihara, K., & Saito, H. (1998). Adaptive changes in membrane lipids of barophilic bacteria in response to changes in growth pressure. Applied Environmental Microbiology, 64(2), 479–485.
• • Yao, J., & Rock, C. O. (2017). Bacterial fatty acid metabolism in modern antibiotic discovery. Biochimica et Biophysica Acta- Molecular and Cell Biology of Lipids, 1862(11), 1300–1309. doi:10.1016/j. bbalip.2016.09.014
• • Ye, J. Z., Lin, X. M., Cheng, Z. X., Su, Y. B., Li, W. X., Ali, F. M., Peng, B. (2018). Identification and efficacy of glycine, serine and threonine metabolism in potentiating kanamycin-mediated killing of Edwardsiella piscicida. Journal of Proteomics, 183, 34–44. doi:10.1016/j.jprot.2018.05.006
• • Zampieri, M., Zimmermann, M., Claassen, M., & Sauer, U. (2017). Nontargeted Metabolomics Reveals the Multilevel Response to Antibiotic Perturbations. Cell Reports, 19(6), 1214–1228. doi:10.1016/j.celrep.2017.04.002