Editorial - Journal of Systems Biology & Proteome Research (2017) Journal of Systems Biology & Proteome Research (Special Issue-2017)
Bacterial metabolomics reveals the evolution of antibiotic resistance.
Eswara Rao T, Ranjith Kumavath*
Department of Genomic Science, School of Biological Sciences, Central University of Kerala, Padanakkad P.O, Kasaragod, Kerala-671314, India
- *Corresponding Author:
- Ranjith Kumavath
Department of Genomic Science
Central University of Kerala
E-mail: [email protected]
Accepted date: July 27, 2017
Citation: Eswara Rao T, Kumavath R. Bacterial metabolomics reveals the evolution of antibiotic resistance. J Syst Biol Proteome Res. 2017;1(1):1-2
The present world crisis to the bacteria enhance towards antibiotic tolerance and the evolution of resistance acquisition. However, it is utmost important to identify novel metabolite reactivity with known drugs effectively enhancing the resistant strains. Monitoring the changing environmental adaption of microbes and the prevalence of Multi-Drug-Resistant (MDR), novel antibiotics that target distinct cellular functions are needed. The new drugs are frequently entering into the market along with the existing drugs. The antibacterial agents can be discussed in five major classes, i.e. classification based on the type of action, source, and spectrum of activity, chemical structure and function. Multi drug resistance of bacteria (Pseudomonas aeruginosa and Staphylococcus aureus.) to antibiotics is an urgent problem of the human race, which leads to the lack of therapy for infectious diseases. Development of new / old drugs has almost ceased in the last decades-even when a new antibiotics is launched, very soon the resistance of bacteria appears. Many clinicians recommend alternative approaches of using antimicrobial substances. However, the misuse and mishandling of drugs lead to microbial, resistance as well as result in the difficulty of treating multidrug resistance organisms. Metabolites are the driving force to rapid adaption on unexpected environmental changes such as stresses and nutrient shifts. The Whole cell metabolite profiling approaches would give rise to a more complete mechanistic insight  Recent reports say the metabolite plays emergence of multidrug resistance. Metabolism is the central role in mediating the early response to antibiotics [2,3]. The metabolites  Involved in the stress response may confer an advantage during infections regulations in response to environmental conditions and also mortality due to bacterial infections is underestimated. Those bacterial responses to environmental factors are related to metabolism. in contrast, the metabolome refers to a complete set of small-molecules with diverse metabolic activity found within a biological sample and can be a very sensitive measure of an organism’s phenotype because metabolites are the final products of enormous genome-wide or proteome-wide interactions . Since, more efforts had focused on target-based discovery leading to an era of screening chemicals for inhibitory activity against protein targets.
It is crucial to understand the detailed mechanisms of antibiotic action and resistance with metabolome scale level . The network express the functionality of biological systems, through observation of changes in the concentration of metabolites as low-molecular weight (<1 kDa) compounds . The end products of the organisms to monitor the gene function and the biochemical status of an organism the interplay between natural selection of resistance mutations and the environment remains unclear. However, the bacteria has been shown to acquire resistance to antibiotics is a very short time period; Escherichia coli was shown to gain resistance to ciprofloxacin in a matter of 10 hours . Novel metabolites such as Gepotidacin , cathelicidin , Rhodethrin , Rubrivivaxin  etc. were discovered by Ranjith Kumavath and his group in the recent past showing promising antimicrobial activity and also enzymes associated with bacterial metabolism of aromatic compounds [13,14]. However, as discussed previously, resistance to any antibiotic is only a matter of time. Hence, there is an urgent need to tackle the current multidrug resistant pathogens.
The promising field of metabolomics, and the closely related areas of metabolomics and metabolite profiling, involve the quantitative detection of multiple small molecule metabolites in biological systems . The mechanisms behind the opportunity to gain a system of cellular biochemical networks under defined conditions and has been increasingly employed in bacterial physiology and drug discovery to elucidate the mechanism of drug action. The metabolisms of cellular lipids, nucleotides, amino sugars and energy are common pathways involved in the bacterial physiology and regrowth occur in a differential time-dependent manner the metabolome of bacterial cells can potentially lead to innovative strategies for effective antibacterial therapy . The opportunistic pathogens influenced by intracellular and extracellular metabolic processes and modulate antibiotic susceptibility in bacteria a deeper understanding of these environmental processes may prove crucial for the development of new antibacterial therapies . The clearer understanding is needed to acquire comprehensive insights into the pathogenesis and antibiotic resistance. A primary issue is our incomplete knowledge of the metabolome; extensive effort is still required to characterize the metabolome from all organisms. The above report provides better understanding the important of the secondary metabolites leads to have high efficacy on virulence and high chances of sustainable antibiotic resistance.
- Biedenbach DJ, Bouchillon SK, Hackel M, Miller LA, Scangarella-Oman NE, Jakielaszek C, Sahm DF. In vitro activity of gepotidacin, a novel triazaacenaphthylene bacterial topoisomerase inhibitor, against a broad spectrum of bacterial pathogens. Antimicrobial agents and chemotherapy. 2016 Jan 4: AAC-02820.
- Bueno J. Metabolomics in antimicrobial drug discovery: the success of the chemical diversity. J. Microb. Biochem. Technol. 2015; 7:380-3.
- Gao W, Xing L, Qu P, Tan T, Yang N, Li D, Chen H, Feng X. Identification of a novel cathelicidin antimicrobial peptide from ducks and determination of its functional activity and antibacterial mechanism. Scientific reports. 2015 Nov 26; 5:17260.
- Gowda GN, Zhang S, Gu H, Asiago V, Shanaiah N, Raftery D. Metabolomics-based methods for early disease diagnostics. Expert review of molecular diagnostics. 2008 Sep 1;8(5):617-33.
- Hoerr V, Duggan GE, Zbytnuik L, Poon KK, Große C, Neugebauer U, Methling K, Löffler B, Vogel HJ. Characterization and prediction of the mechanism of action of antibiotics through NMR metabolomics. BMC microbiology. 2016 May 10; 16(1):82.
- Imchen M, Kumavath R. Vaccination to Combat as an Approach to Reduce the Antibacterial Resistance..! Int J Vaccines Vaccine. (2017 4(1): 00074.
- Kumavath RN, Ramana CV, Sasikala C. Rubrivivaxin, a new cytotoxic and cyclooxygenase-I inhibitory metabolite from Rubrivivaxbenzoatilyticus JA2. World Journal of Microbiology and Biotechnology. 2011 Jan 1; 27(1):11-6.
- Lee HH, Collins JJ. Microbial environments confound antibiotic efficacy. Nature chemical biology. 2012 Jan 1; 8(1):6-9.
- Maifiah MH, Creek DJ, Nation RL, Forrest A, Tsuji BT, Velkov T, Li J. Untargeted metabolomics analysis reveals key pathways responsible for the synergistic killing of colistin and doripenem combination against Acinetobacterbaumannii. Scientific Reports. 2017;7.
- Kumavath RN, Barh D, Azevedo V, Kumar AP. Potential pharmacological applications of enzymes associated with bacterial metabolism of aromatic compounds. Journal of Microbiology and Antimicrobials. 2017 Jan 31; 9(1):1-3.
- Dhanasekaran D, Thajuddin N, Panneerselvam A, editors. Antimicrobials: Synthetic and Natural Compounds. CRC Press; 2015 Dec 1.
- Ranjith NK, Sasikala C, Ramana CV. Rhodethrin: a novel indoleterpenoid ether produced by Rhodobactersphaeroides has cytotoxic and phytohormonal activities. Biotechnology letters. 2007 Sep 1; 29(9):1399-402.
- Vincent IM, Ehmann DE, Mills SD, Perros M, Barrett MP. Untargeted metabolomics to ascertain antibiotic modes of action. Antimicrobial agents and chemotherapy. 2016 Apr 1;60(4):2281-91.
- Wang Z, Li MY, Peng B, Cheng ZX, Li H, Peng XX. GC?MS-based metabolome and metabolite regulation in serum-resistant Streptococcus agalactiae. Journal of proteome research. 2016 Jun 13; 15(7):2246-53.
- Zampieri M, Enke T, Chubukov V, Ricci V, Piddock L, Sauer U. Metabolic constraints on the evolution of antibiotic resistance. Molecular systems biology. 2017 Mar 1;13(3):917.
- Zampieri M, Zimmermann M, Claassen M, Sauer U. Nontargeted Metabolomics Reveals the Multilevel Response to Antibiotic Perturbations. Cell Reports. 2017 May 9; 19(6):1214-28.
- Zhang Q, Lambert G, Liao D, Kim H, Robin K, Tung CK, Pourmand N, Austin RH. Acceleration of emergence of bacterial antibiotic resistance in connected microenvironments. Science. 2011 Sep 23; 333(6050):1764-7.