Metabolomics in drug discovery: Restoring antibiotic pipeline

Faiza Azhar , Mariam Busharat , Shah Rukh Arshad Chaudhary , Zainab Waheed , Muhammad Nauman Jamil

Asian Pacific Journal of Tropical Biomedicine ›› 2023, Vol. 13 ›› Issue (9) : 378 -383.

PDF (465KB)
Asian Pacific Journal of Tropical Biomedicine ›› 2023, Vol. 13 ›› Issue (9) :378 -383. DOI: 10.4103/2221-1691.385568
Review Article
research-article
Metabolomics in drug discovery: Restoring antibiotic pipeline
Author information +
History +
PDF (465KB)

Abstract

Metabolomics has emerged as a valuable tool in drug discovery and development, providing new insights into the mechanisms of action and toxicity of potential therapeutic agents. Metabolomics focuses on the comprehensive analysis of primary as well as secondary metabolites, within biological systems. Metabolomics provides a comprehensive understanding of the metabolic changes that occur within microbial pathogens when exposed to therapeutic agents, thus allowing for the identification of unique metabolic targets that can be exploited for therapeutic intervention. This approach can also uncover key metabolic pathways essential for survival, which can serve as potential targets for novel antibiotics. By analyzing the metabolites produced by diverse microbial communities, metabolomics can guide the discovery of previously unexplored sources of antibiotics. This review explores some examples that enable medicinal chemists to optimize drug structure, enhancing efficacy and minimizing toxicity via metabolomic approaches.

Keywords

Metabolomics / Infectious diseases / Drug discovery / Antibiotics / Biomarkers

Cite this article

Download citation ▾
Faiza Azhar, Mariam Busharat, Shah Rukh Arshad Chaudhary, Zainab Waheed, Muhammad Nauman Jamil. Metabolomics in drug discovery: Restoring antibiotic pipeline. Asian Pacific Journal of Tropical Biomedicine, 2023, 13 (9) : 378-383 DOI:10.4103/2221-1691.385568

登录浏览全文

4963

注册一个新账户 忘记密码

Conflict of interest statement

The authors declare no conflict of interest.

Funding

The authors received no extramural funding for the study.

Authors’ contributions

FA and MB designed the manuscript, SRAC and ZW were involved in data collection required for figures. FA and MNJ edited the final version of manuscript.

References

[1]

Wishart DS. Applications of metabolomics in drug discovery and development. Drugs R D 2008; 9(5): 307-322.

[2]

Robertson DG, Frevert U. Metabolomics in drug discovery and development. Clin Pharmacol Ther 2013; 94(5): 559-561.

[3]

Fraga-Corral M, Carpena M, Garcia-Oliveira P, Pereira AG, Prieto MA, Simal-Gandara J. Analytical metabolomics and applications in health, environmental and food science. Crit Rev Anal Chem 2022; 52(4): 712-734.

[4]

Hoerr V, Duggan GE, Zbytnuik L, Poon KKH, Große C, Neugebauer U, et al. Characterization and prediction of the mechanism of action of antibiotics through NMR metabolomics. BMC Microbiol 2016; 16(82): 1-14.

[5]

Kantae V, Krekels EHJ, Esdonk MJV, Lindenburg P, Harms AC, Knibbe CAJ, et al. Integration of pharmacometabolomics with pharmacokinetics and pharmacodynamics: Towards personalized drug therapy. Metabolomics 2017; 13(9): 1-11.

[6]

Weber RJM, Lawson TN, Salek RM, Ebbels TMD, Glen RC, Goodacre R, et al. Computational tools and workflows in metabolomics: An international survey highlights the opportunity for harmonisation through Galaxy. Metabolomics 2017; 13(12): 1-5.

[7]

Aminov R. Metabolomics in antimicrobial drug discovery. Expert Opin Drug Discov 2022; 17(9): 1047-1059.

[8]

Tounta V, Liu Y, Cheyne A, Larrouy-Maumus G. Metabolomics in infectious diseases and drug discovery. Mol Omics 2021; 17(3): 376-393.

[9]

Ludwig KR, Hummon AB. Mass spectrometry for the discovery of biomarkers of sepsis. Mol Biosyst 2017; 13(4): 648-664.

[10]

Zhang A, Sun H, Wang X. Saliva metabolomics opens door to biomarker discovery, disease diagnosis, and treatment. Appl Biochem Biotechnol 2012; 168: 1718-1727.

[11]

Zeiss DR, Mhlongo MI, Tugizimana F, Steenkamp PA, Dubery IA. Metabolomic profiling of the host response of tomato (Solanum lycopersicum) following infection by Ralstonia solanacearum. Int J Mol Sci 2019; 20(16): 3945-3967.

[12]

Pacchiarotta T, Hensbergen PJ, Wuhrer M, van Nieuwkoop C, Nevedomskaya E, Derks RJE, et al. Fibrinogen alpha chain O-glycopeptides as possible markers of urinary tract infection. J Proteom 2012; 75(3): 1067-1073.

[13]

Bilal H, Khan MN, Rehman T, Hameed MF, Yang X. Antibiotic resistance in Pakistan: A systematic review of past decade. BMC Infect Dis 2021; 21(1): 1-19.

[14]

Piddock LJV. Teixobactin, the first of a new class of antibiotics discovered by iChip technology? J Antimicrob Chemother 2015; 70(10): 2679-2680.

[15]

Lee YR, Burton CE. Eravacycline, a newly approved fluorocycline. Eur J Clin Microbiol Infect Dis 2019; 38: 1787-1794.

[16]

Panter F, Bader CD, Müller RJCS. Synergizing the potential of bacterial genomics and metabolomics to find novel antibiotics. Chem Sci 2021; 12(17): 5994-6010.

[17]

Lu QP, Huang YM, Liu SW, Wu G, Yang Q, Liu LF, et al. Metabolomics tools assisting classic screening methods in discovering new antibiotics from mangrove actinomycetia in Leizhou peninsula. Mar Drugs 2021; 19(12): 688-718.

[18]

Hou Y, Braun DR, Michel CR, Klassen JL, Adnani N, Wyche TP, et al. Microbial strain prioritization using metabolomics tools for the discovery of natural products. Anal Chem 2012; 84(10): 4277-4283.

[19]

Robertson GT, Bonventre EJ, Doyle TB, Du Q, Duncan L, Morris TW, et al. In vitro evaluation of CBR-2092, a novel rifamycin-quinolone hybrid antibiotic: Microbiology profiling studies with staphylococci and streptococci. Antimicrob Agents Chemother 2008; 52(7): 2324-2334.

[20]

Mukhtar TA, Koteva KP, Wright GD. Chimeric streptogramin-tyrocidine antibiotics that overcome streptogramin resistance. Chem Biol 2005; 12(2): 229-235.

[21]

Peek J, Koirala B, Brady SF. Synthesis and evaluation of dual-action kanglemycin-fluoroquinolone hybrid antibiotics. Bioorg Med Chem Lett 2022; 57. doi: 10.1016/j.bmcl.2021.128484.

[22]

Domalaon R, Idowu T, Zhanel GG, Schweizer F. Antibiotic hybrids: The next generation of agents and adjuvants against Gram-negative pathogens? Clin Microbiol Rev 2018; 31(2). doi: 10.1128/CMR.00077-17.

[23]

Ma Z, He S, Yuan Y, Zhuang Z, Liu Y, Wang H, et al. Design, synthesis, and characterization of TNP-2198, a dual-targeted rifamycin-nitroimidazole conjugate with potent activity against microaerophilic and anaerobic bacterial pathogens. J Med Chem 2022; 65(6): 4481-4495.

[24]

Vincent IM, Ehmann DE, Mills SD, Perros M, Barrett MP. Untargeted metabolomics to ascertain antibiotic modes of action. Antimicrob Agents Chemother 2016; 60(4): 2281-2291.

[25]

Alarcon-Barrera JC, Kostidis S, Ondo-Mendez A, Giera M. Recent advances in metabolomics analysis for early drug development. Drug Discovery Today 2022; 27(6): 1763-1773.

[26]

Halouska S, Fenton RJ, Barletta RG, Powers R. Predicting the in vivo mechanism of action for drug leads using NMR metabolomics. ACS Chem Biol 2012; 7(1): 166-171.

[27]

Bueno J. Metabolomics in antimicrobial drug discovery: The success of the chemical diversity. J Microb Biochem Technol 2015; 7: 380-383.

[28]

Sieniawska E, Georgiev MI. Metabolomics: Towards acceleration of antibacterial plant-based leads discovery. Phytochem Rev 2021; 21(3): 765-781.

[29]

Wu C, Choi YH, van Wezel GP. Metabolic profiling as a tool for prioritizing antimicrobial compounds. J Ind Microbiol Biotechnol 2016; 43(2): 299-312.

[30]

Konstantinidis T, Tsigalou C, Karvelas A, Stavropoulou E, Voidarou C, Bezirtzoglou E. Effects of antibiotics upon the gut microbiome: A review of the literature. Biomedicines 2020; 8(11): 502.

[31]

Robles M, Toscano E, Cotta J, Lucena MI, Andrade RJ. Antibiotic-induced liver toxicity: Mechanisms, clinical features and causality assessment. Curr Drug Saf 2010; 5(3): 212-222.

[32]

Ryu SH, Kim JW, Yoon D, Kim S, Kim KB. Serum and urine toxicometabolomics following gentamicin-induced nephrotoxicity in male Sprague-Dawley rats. J Toxicol Environ Health Part A 2018; 81(11): 408-420.

[33]

Rawat A, Dubey D, Guleria A, Kumar U, Keshari AK, Chaturvedi S, et al. (1)H NMR-based serum metabolomics reveals erythromycin-induced liver toxicity in albino Wistar rats. J Pharm Bioallied Sci 2016; 8(4): 327-334.

[34]

Chong J, Xia J. Using MetaboAnalyst 4.0 for metabolomics data analysis, interpretation, and integration with other omics data. In: Li S (ed.) Computational methods and data analysis for metabolomics. New York: E-publishing Inc; 2020, p. 337-360.

[35]

Mussap M, Zaffanello M, Fanos V. Metabolomics: A challenge for detecting and monitoring inborn errors of metabolism. Ann Transl Med 2018; 6(17): 338.

[36]

Ellis JK, Athersuch TJ, Thomas LDK, Teichert F, Pérez-Trujillo M, Svendsen C, et al. Metabolic profiling detects early effects of environmental and lifestyle exposure to cadmium in a human population. BMC Med 2012; 10(1): 61.

[37]

Chen PC, Zhang WZ, Chen WR, Jair YC, Wu YH, Liu YH, et al. Engineering an integrated system with a high pressure polymeric microfluidic chip coupled to liquid chromatography-mass spectrometry (LC-MS) for the analysis of abused drugs. Sens Actuators B Chem 2022; 350: 130888.

[38]

Winkler DA, Mombelli E, Pietroiusti A, Tran L, Worth A, Fadeel B, et al. Applying quantitative structure-activity relationship approaches to nanotoxicology: Current status and future potential. Toxicology 2013; 313(1): 15-23.

[39]

Schnackenberg LK, Sun J, Beger RD. Metabolomics techniques in nanotoxicology studies. In: Reineke J (ed.) Nanotoxicity: Methods and protocols. New Jersey: E-publishing Inc; 2012, p. 141-156.

[40]

Ramallo IA, Salazar MO, Mendez L, Furlan RL. Chemically engineered extracts: source of bioactive compounds. Acc Chem Res 2011; 44(4): 241-250.

[41]

Boonchaisri S, Rochfort S, Stevenson T, Dias DA. Recent developments in metabolomics-based research in understanding transgenic grass metabolism. Metabolomics 2019; 15(4): 47.

PDF (465KB)

0

Accesses

0

Citation

Detail

Sections
Recommended

/