Skip to main content

Omics and In Silico Approaches in the Surveillance and Monitoring of Antimicrobial Resistance

  • Chapter
  • First Online:
Emerging Modalities in Mitigation of Antimicrobial Resistance

Abstract

Antimicrobial resistance (AMR) is mounting at a distressing rate; diseases that were once curable have now turned out to be frequent public health crisis. This has led to the realization that extensive research must be conducted to mitigate the manifestation and spread of AMR. The mode of action of antimicrobial agents can influence the cellular pathways of microbes that are under genetic control. These pathways involved in antimicrobial resistance can be recognized more efficiently by combining genomics, transcriptomics, proteomics, and metabolomics. The precise and speedy determination of antimicrobial resistance is pivotal in treating an infection and in reducing antibiotic abuse. Today, detection and characterization of AMR have moved from culture techniques and PCR to metagenomics via next-generation sequencing techniques; therefore, suitable tools for examining large-scale data are needed. The increasing access to high-throughput quantitative PCR, microarray, and high-throughput sequencing (HTS) has enabled the identification of many AMR determinants. Extensive comparative studies of organismal and environmental samples have thrown light into the comprehensive spread of antimicrobial resistance genes (ARGs) and the dispersal of multidrug-resistant bacteria, resistance exchange networks, and different habitats and phylogeny that affect the evolutionary dynamics of AMR. Exploring genetic factors contributing to AMR using sequence data poses specific issues that are being tackled by advancements in algorithms and in silico tools that orchestrate genomic data and predict AMR. This chapter focuses on omic approaches, bioinformatic tools, and databases used for studying antimicrobial resistance.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Alcock BP, Raphenya AR, Lau TTY, Tsang KK, Bouchard M, Edalatmand A et al (2020) CARD 2020: antibiotic resistome surveillance with the comprehensive antibiotic resistance database. Nucleic Acids Res 48(D1):D517–D525

    CAS  PubMed  Google Scholar 

  • Alekshun MN, Levy SB (2007) Molecular mechanisms of antibacterial multidrug resistance. Cell 128(6):1037–1050

    Article  CAS  PubMed  Google Scholar 

  • Amsalu A, Sapula SA, De Barros LM, Hart BJ, Nguyen AH, Drigo B et al (2020) Efflux pump-driven antibiotic and biocide cross-resistance in Pseudomonas aeruginosa isolated from different ecological niches: a case study in the development of multidrug resistance in environmental hotspots. Microorganisms 8(11):1647

    Article  CAS  PubMed Central  Google Scholar 

  • Andersson DI (2003) Persistence of antibiotic resistant bacteria. Curr Opin Microbiol 6(5):452–456

    Article  CAS  PubMed  Google Scholar 

  • Andersson DI (2006) The biological cost of mutational antibiotic resistance: any practical conclusions? Curr Opin Microbiol 9(5):461–465

    Article  CAS  PubMed  Google Scholar 

  • Arango-Argoty GA, Guron GKP, Garner E, Riquelme MV, Heath LS, Pruden A et al (2020) ARGminer: a web platform for the crowdsourcing-based curation of antibiotic resistance genes. Bioinformatics 36(9):2966–2973

    Article  CAS  PubMed  Google Scholar 

  • Basheera V (2020) Global antimicrobial resistance; a peek in to the GLASS data. Asian J Pharm Health Sci [Internet] [cited 2021 Apr 24];10(1). http://ajphs.com/article/2020/10/1/2197-2207

  • Berglund F, Österlund T, Boulund F, Marathe NP, Larsson DGJ, Kristiansson E (2019) Identification and reconstruction of novel antibiotic resistance genes from metagenomes. Microbiome 7(1):52

    Article  PubMed  PubMed Central  Google Scholar 

  • Birkenstock T, Liebeke M, Winstel V, Krismer B, Gekeler C, Niemiec MJ et al (2012) Exometabolome analysis identifies pyruvate dehydrogenase as a target for the antibiotic triphenylbismuthdichloride in multiresistant bacterial pathogens. J Biol Chem 287(4):2887–2895

    Article  CAS  PubMed  Google Scholar 

  • Boolchandani M, Patel S, Dantas G (2017) Functional metagenomics to study antibiotic resistance. Methods Mol Biol 1520:307–329

    Article  CAS  PubMed  Google Scholar 

  • Boolchandani M, D’Souza AW, Dantas G (2019) Sequencing-based methods and resources to study antimicrobial resistance. Nat Rev Genet 20(6):356–370

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bortolaia V, Kaas RS, Ruppe E, Roberts MC, Schwarz S, Cattoir V et al (2020) ResFinder 4.0 for predictions of phenotypes from genotypes. J Antimicrob Chemother 75(12):3491–3500

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bradley P, Gordon NC, Walker TM, Dunn L, Heys S, Huang B et al (2015) Rapid antibiotic-resistance predictions from genome sequence data for Staphylococcus aureus and Mycobacterium tuberculosis. Nat Commun 6(1):10063

    Article  CAS  PubMed  Google Scholar 

  • Bush K (2018) Past and present perspectives on β-lactamases. Antimicrob Agents Chemother [Internet] [cited 2021 Mar 18];62(10). https://aac.asm.org/content/62/10/e01076-18

  • Caruana JC, Walper SA (2020) Bacterial membrane vesicles as mediators of microbe – microbe and microbe – host community interactions. Front Microbiol [Internet] [cited 2021 Mar 19];11. https://www.frontiersin.org/articles/10.3389/fmicb.2020.00432/full

  • Casneuf T, Van de Peer Y, Huber W (2007) In situ analysis of cross-hybridisation on microarrays and the inference of expression correlation. BMC Bioinformatics 8(1):461

    Article  PubMed  PubMed Central  Google Scholar 

  • Chan K-G (2016) Whole-genome sequencing in the prediction of antimicrobial resistance. Expert Rev Anti-Infect Ther 14(7):617–619

    Article  CAS  PubMed  Google Scholar 

  • Chandra Mohana N, Yashavantha Rao HC, Rakshith D, Mithun PR, Nuthan BR, Satish S (2018) Omics based approach for biodiscovery of microbial natural products in antibiotic resistance era. J Genet Eng Biotechnol 16(1):1–8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chernov VM, Chernova OA, Mouzykantov AA, Lopukhov LL, Aminov RI (2019) Omics of antimicrobials and antimicrobial resistance. Expert Opin Drug Discov 14(5):455–468

    Article  CAS  PubMed  Google Scholar 

  • Clausen PTLC, Aarestrup FM, Lund O (2018) Rapid and precise alignment of raw reads against redundant databases with KMA. BMC Bioinformatics 19(1):307

    Article  PubMed  PubMed Central  Google Scholar 

  • Coenen S, Ferech M, Haaijer-Ruskamp FM, Butler CC, Stichele RHV, Verheij TJM et al (2007) European Surveillance of Antimicrobial Consumption (ESAC): quality indicators for outpatient antibiotic use in Europe. Qual Saf Health Care 16(6):440–445

    Article  PubMed  PubMed Central  Google Scholar 

  • Dersch P, Khan MA, Mühlen S, Görke B (2017) Roles of regulatory RNAs for antibiotic resistance in bacteria and their potential value as novel drug targets. Front Microbiol [Internet] [cited 2021 Mar 19];8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5418344/

  • Doster E, Lakin SM, Dean CJ, Wolfe C, Young JG, Boucher C et al (2020) MEGARes 2.0: a database for classification of antimicrobial drug, biocide and metal resistance determinants in metagenomic sequence data. Nucleic Acids Res 48(D1):D561–D569

    Article  CAS  PubMed  Google Scholar 

  • European Centre for Disease Prevention and Control (2021a) About the network [Internet] [cited 2021 Apr 24]. https://www.ecdc.europa.eu/en/about-us/partnerships-and-networks/disease-and-laboratory-networks/esac-net-about

  • European Centre for Disease Prevention and Control (2021b) European Antimicrobial Resistance Surveillance Network (EARS-Net) [Internet] [cited 2021 Apr 24]. https://www.ecdc.europa.eu/en/about-us/partnerships-and-networks/disease-and-laboratory-networks/ears-net

  • Feldgarden M, Brover V, Haft DH, Prasad AB, Slotta DJ, Tolstoy I et al (2019) Validating the AMRFinder tool and resistance gene database by using antimicrobial resistance genotype-phenotype correlations in a collection of isolates. Antimicrob Agents Chemother 63(11):e00483

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ganguly NK, Arora NK, Chandy SJ, Fairoze MN, Gill JP, Gupta U et al (2011) Rationalizing antibiotic use to limit antibiotic resistance in India. Indian J Med Res 134:281–294

    PubMed  Google Scholar 

  • Gawronski JD, Wong SMS, Giannoukos G, Ward DV, Akerley BJ (2009) Tracking insertion mutants within libraries by deep sequencing and a genome-wide screen for Haemophilus genes required in the lung. Proc Natl Acad Sci U S A 106(38):16422–16427

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Geisinger E, Mortman NJ, Vargas-Cuebas G, Tai AK, Isberg RR (2018) A global regulatory system links virulence and antibiotic resistance to envelope homeostasis in Acinetobacter baumannii. PLoS Pathog 14(5):e1007030

    Article  PubMed  PubMed Central  Google Scholar 

  • Gilbert JM, White DG, McDermott PF (2007) The US national antimicrobial resistance monitoring system. Future Microbiol 2(5):493–500

    Article  CAS  PubMed  Google Scholar 

  • Goodman AL, McNulty NP, Zhao Y, Leip D, Mitra RD, Lozupone CA et al (2009) Identifying genetic determinants needed to establish a human gut symbiont in its habitat. Cell Host Microbe 6(3):279–289

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Handel A, Regoes RR, Antia R (2006) The role of compensatory mutations in the emergence of drug resistance. PLoS Comput Biol 2(10):e137

    Article  PubMed  PubMed Central  Google Scholar 

  • He Y, Zhou X, Chen Z, Deng X, Gehring A, Ou H et al (2020) PRAP: Pan Resistome analysis pipeline. BMC Bioinformatics 21(1):20

    Article  PubMed  PubMed Central  Google Scholar 

  • Hendriksen RS, Bortolaia V, Tate H, Tyson GH, Aarestrup FM, McDermott PF (2019) Using genomics to track global antimicrobial resistance. Front Public Health [Internet] [cited 2021 Mar 6];7. https://www.frontiersin.org/articles/10.3389/fpubh.2019.00242/full

  • Holmes CN, Chiller TM (2004) National Antibiotic Resistance Monitoring System for enteric bacteria. Emerg Infect Dis 10(11):2061

    Article  PubMed Central  Google Scholar 

  • Idle JR, Gonzalez FJ (2007) Metabolomics. Cell Metab 6(5):348–351

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Interagency Coordination Group on Antimicrobial Resistance (2019) No time to wait: securing the future from drug-resistant infections. World Health Organization [cited 2021 Apr 25]. https://www.who.int/antimicrobial-resistance/interagency-coordinationgroup/IACG_final_report_EN.pdf?ua=1

  • Joshi S, Ray P, Manchanda V, Bajaj J, Chitnis DS, Gautam V et al (2013) Methicillin resistant Staphylococcus aureus (MRSA) in India: prevalence & susceptibility pattern. Indian J Med Res 137(2):363–369

    PubMed Central  Google Scholar 

  • Khodadadi E, Zeinalzadeh E, Taghizadeh S, Mehramouz B, Kamounah FS, Khodadadi E et al (2020) Proteomic applications in antimicrobial resistance and clinical microbiology studies. Infect Drug Resist 13:1785–1806

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kleinheinz KA, Joensen KG, Larsen MV (2014) Applying the ResFinder and VirulenceFinder web-services for easy identification of acquired antibiotic resistance and E. coli virulence genes in bacteriophage and prophage nucleotide sequences. Bacteriophage 4(2):e27943

    Article  PubMed  PubMed Central  Google Scholar 

  • Kukurba KR, Montgomery SB (2015) RNA sequencing and analysis. Cold Spring Harb Protoc 2015(11):951–969

    Article  PubMed  PubMed Central  Google Scholar 

  • Lakin SM, Kuhnle A, Alipanahi B, Noyes NR, Dean C, Muggli M et al (2019) Hierarchical Hidden Markov models enable accurate and diverse detection of antimicrobial resistance sequences. Commun Biol [Internet] [cited 2021 Mar 21];2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6684577/

  • Lal Gupta C, Kumar Tiwari R, Cytryn E (2020) Platforms for elucidating antibiotic resistance in single genomes and complex metagenomes. Environ Int 138:105667

    Article  PubMed  Google Scholar 

  • Langridge GC, Phan M-D, Turner DJ, Perkins TT, Parts L, Haase J et al (2009) Simultaneous assay of every salmonella Typhi gene using one million transposon mutants. Genome Res 19(12):2308–2316

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Levy SB, Marshall B (2004) Antibacterial resistance worldwide: causes, challenges and responses. Nat Med 10(12):S122–S129

    Article  CAS  PubMed  Google Scholar 

  • Liu B, Pop M (2009) ARDB—Antibiotic Resistance Genes Database. Nucleic Acids Res 37(suppl_1):D443–D447

    Article  CAS  PubMed  Google Scholar 

  • Martínez JL, Rojo F (2011) Metabolic regulation of antibiotic resistance. FEMS Microbiol Rev 35(5):768–789

    Article  PubMed  Google Scholar 

  • McArthur AG, Wright GD (2015) Bioinformatics of antimicrobial resistance in the age of molecular epidemiology. Antimicrob Microb Syst Biol 27:45–50

    Google Scholar 

  • Medvedeva ES, Davydova MN, Mouzykantov AA, Baranova NB, Grigoreva TY, Siniagina MN et al (2016) Genomic and proteomic profiles of Acholeplasma laidlawii strains differing in sensitivity to ciprofloxacin. Dokl Biochem Biophys 466(1):23–27

    Article  CAS  PubMed  Google Scholar 

  • Mohr KI (2016) History of antibiotics research. Curr Top Microbiol Immunol 398:237–272

    CAS  PubMed  Google Scholar 

  • de Nies L, Lopes S, Busi SB, Galata V, Heintz-Buschart A, Laczny CC et al (2021) PathoFact: a pipeline for the prediction of virulence factors and antimicrobial resistance genes in metagenomic data. Microbiome 9(1):49

    Article  PubMed  PubMed Central  Google Scholar 

  • van Opijnen T, Camilli A (2012) A fine scale phenotype–genotype virulence map of a bacterial pathogen. Genome Res 22(12):2541–2551

    Article  PubMed  PubMed Central  Google Scholar 

  • van Opijnen T, Levin HL (2020) Transposon insertion sequencing, a global measure of gene function. Annu Rev Genet 54(1):337–365

    Article  PubMed  Google Scholar 

  • Pan American Journal of Public Health. Special issue on antimicrobial resistance, vol 30, no. 6. December 2011 - PAHO/WHO | Pan American Health Organization [Internet] [cited 2021 Apr 24]. https://www.paho.org/en/documents/pan-american-journal-public-health-special-issue-antimicrobial-resistance-vol-30-no-6-0

  • Peng B, Li H, Peng X (2019) Proteomics approach to understand bacterial antibiotic resistance strategies. Expert Rev Proteomics 16(10):829–839

    Article  CAS  PubMed  Google Scholar 

  • Pérez-Llarena FJ, Bou G (2016) Proteomics as a tool for studying bacterial virulence and antimicrobial resistance. Front Microbiol [Internet] [cited 2021 Apr 25];7. https://www.frontiersin.org/articles/10.3389/fmicb.2016.00410/full

  • Piddock LJV (2006) Multidrug-resistance efflux pumps - not just for resistance. Nat Rev Microbiol 4(8):629–636

    Article  CAS  PubMed  Google Scholar 

  • Ruppé E, Ghozlane A, Tap J, Pons N, Alvarez A-S, Maziers N et al (2019) Prediction of the intestinal resistome by a three-dimensional structure-based method. Nat Microbiol 4(1):112–123

    Article  PubMed  Google Scholar 

  • Schena M, Shalon D, Davis RW, Brown PO (1995) Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science 270(5235):467–470

    Article  CAS  PubMed  Google Scholar 

  • Singh-Moodley A, Ismail H, Perovic O (2018) An overview of antimicrobial resistance surveillance among healthcare-associated pathogens in South Africa. Afr J Lab Med 7(2):1–6

    Article  Google Scholar 

  • Torres-Cortés G, Millán V, Ramírez-Saad HC, Nisa-Martínez R, Toro N, Martínez-Abarca F (2011) Characterization of novel antibiotic resistance genes identified by functional metagenomics on soil samples. Environ Microbiol 13(4):1101–1114

    Article  PubMed  Google Scholar 

  • Vila J, Martí S, Sánchez-Céspedes J (2007) Porins, efflux pumps and multidrug resistance in Acinetobacter baumannii. J Antimicrob Chemother 59(6):1210–1215

    Article  CAS  PubMed  Google Scholar 

  • Wenzel M, Bandow JE (2011) Proteomic signatures in antibiotic research. Proteomics 11(15):3256–3268

    Article  CAS  PubMed  Google Scholar 

  • Winters C, Gelband H (2011) Part I. The global antibiotic resistance partnership (GARP). S Afr Med J 101(8 pt 2):556–557

    CAS  PubMed  Google Scholar 

  • Wright GD (2007) The antibiotic resistome: the nexus of chemical and genetic diversity. Nat Rev Microbiol 5(3):175–186

    Article  CAS  PubMed  Google Scholar 

  • Yang Y, Jiang X, Chai B, Ma L, Li B, Zhang A et al (2016) ARGs-OAP: online analysis pipeline for antibiotic resistance genes detection from metagenomic data using an integrated structured ARG-database. Bioinformatics 32(15):2346–2351

    Article  CAS  PubMed  Google Scholar 

  • Yang J, Kim EK, McDowell A, Kim Y-K (2018) Microbe-derived extracellular vesicles as a smart drug delivery system. Transl Clin Pharmacol 26(3):103

    Article  PubMed  PubMed Central  Google Scholar 

  • Yin X, Jiang X-T, Chai B, Li L, Yang Y, Cole JR et al (2018) ARGs-OAP v2.0 with an expanded SARG database and Hidden Markov models for enhancement characterization and quantification of antibiotic resistance genes in environmental metagenomes. Bioinformatics 34(13):2263–2270

    Article  CAS  PubMed  Google Scholar 

  • Zampieri M, Enke T, Chubukov V, Ricci V, Piddock L, Sauer U (2017) Metabolic constraints on the evolution of antibiotic resistance. Mol Syst Biol [Internet] [cited 2021 Apr 25];13(3). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5371735/

  • Zankari E, Hasman H, Cosentino S, Vestergaard M, Rasmussen S, Lund O et al (2012) Identification of acquired antimicrobial resistance genes. J Antimicrob Chemother 67(11):2640–2644

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zankari E, Allesøe R, Joensen KG, Cavaco LM, Lund O, Aarestrup FM (2017) PointFinder: a novel web tool for WGS-based detection of antimicrobial resistance associated with chromosomal point mutations in bacterial pathogens. J Antimicrob Chemother 72(10):2764–2768

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang W, Li F, Nie L (2010) Integrating multiple “omics” analysis for microbial biology: application and methodologies. Microbiol Read Engl 156(Pt 2):287–301

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to S. Sudheer Khan .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2022 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Thomas, A.M., Raju, L.L., Khan, S.S. (2022). Omics and In Silico Approaches in the Surveillance and Monitoring of Antimicrobial Resistance. In: Akhtar, N., Singh, K.S., Prerna, Goyal, D. (eds) Emerging Modalities in Mitigation of Antimicrobial Resistance. Springer, Cham. https://doi.org/10.1007/978-3-030-84126-3_16

Download citation

Publish with us

Policies and ethics