Skip to main content
  • ASM
    • Antimicrobial Agents and Chemotherapy
    • Applied and Environmental Microbiology
    • Clinical Microbiology Reviews
    • Clinical and Vaccine Immunology
    • EcoSal Plus
    • Eukaryotic Cell
    • Infection and Immunity
    • Journal of Bacteriology
    • Journal of Clinical Microbiology
    • Journal of Microbiology & Biology Education
    • Journal of Virology
    • mBio
    • Microbiology and Molecular Biology Reviews
    • Microbiology Resource Announcements
    • Microbiology Spectrum
    • Molecular and Cellular Biology
    • mSphere
    • mSystems
  • Log in
  • My alerts
  • My Cart

Main menu

  • Home
  • Articles
    • Latest Articles
    • COVID-19 Special Collection
    • Archive
  • For Authors
    • Submit a Manuscript
    • Scope
    • Editorial Policy
    • Submission, Review, & Publication Processes
    • Organization and Format
    • Errata, Author Corrections
    • Illustrations and Tables
    • Nomenclature
    • Abbreviations and Conventions
    • Ethics Resources and Policies
  • About the Journal
    • About MMBR
    • Editor in Chief
    • Editorial Board
    • For Reviewers
    • For the Media
    • For Librarians
    • For Advertisers
    • Alerts
    • RSS
    • FAQ
  • Subscribe
    • Members
    • Institutions
  • ASM
    • Antimicrobial Agents and Chemotherapy
    • Applied and Environmental Microbiology
    • Clinical Microbiology Reviews
    • Clinical and Vaccine Immunology
    • EcoSal Plus
    • Eukaryotic Cell
    • Infection and Immunity
    • Journal of Bacteriology
    • Journal of Clinical Microbiology
    • Journal of Microbiology & Biology Education
    • Journal of Virology
    • mBio
    • Microbiology and Molecular Biology Reviews
    • Microbiology Resource Announcements
    • Microbiology Spectrum
    • Molecular and Cellular Biology
    • mSphere
    • mSystems

User menu

  • Log in
  • My alerts
  • My Cart

Search

  • Advanced search
Microbiology and Molecular Biology Reviews
publisher-logosite-logo

Advanced Search

  • Home
  • Articles
    • Latest Articles
    • COVID-19 Special Collection
    • Archive
  • For Authors
    • Submit a Manuscript
    • Scope
    • Editorial Policy
    • Submission, Review, & Publication Processes
    • Organization and Format
    • Errata, Author Corrections
    • Illustrations and Tables
    • Nomenclature
    • Abbreviations and Conventions
    • Ethics Resources and Policies
  • About the Journal
    • About MMBR
    • Editor in Chief
    • Editorial Board
    • For Reviewers
    • For the Media
    • For Librarians
    • For Advertisers
    • Alerts
    • RSS
    • FAQ
  • Subscribe
    • Members
    • Institutions
Review

Origins and Evolution of Antibiotic Resistance

Julian Davies, Dorothy Davies
Julian Davies
Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia V6T 1Z3, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: jed@interchange.ubc.ca
Dorothy Davies
Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia V6T 1Z3, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1128/MMBR.00016-10
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Article Figures & Data

Figures

  • Tables
  • FIG. 1.
    • Open in new tab
    • Download powerpoint
    FIG. 1.

    History of antibiotic discovery and concomitant development of antibiotic resistance. The dark ages, the preantibiotic era; primordial, the advent of chemotherapy, via the sulfonamides; golden, the halcyon years when most of the antibiotics used today were discovered; the lean years, the low point of new antibiotic discovery and development; pharmacologic, attempts were made to understand and improve the use of antibiotics by dosing, administration, etc.; biochemical, knowledge of the biochemical actions of antibiotics and resistance mechanisms led to chemical modification studies to avoid resistance; target, mode-of-action and genetic studies led to efforts to design new compounds; genomic/HTS, genome sequencing methodology was used to predict essential targets for incorporation into high-throughput screening assays; disenchantment, with the failure of the enormous investment in genome-based methods, many companies discontinued their discovery programs. Other milestones in this history include the creation of the FDA Office of New Drugs after the thalidomide disaster led to stricter requirements for drug safety, including the use of antibiotics. This slowed the registration of novel compounds. Before antibiotics were discovered, Semmelweis advocated hand washing as a way of avoiding infection; this practice is now strongly recommended as a method to prevent transmission.

  • FIG. 2.
    • Open in new tab
    • Download powerpoint
    FIG. 2.

    Numbers of unique β-lactamase enzymes identified since the introduction of the first β-lactam antibiotics. (Up-to-date numbers are courtesy of Karen Bush.)

  • FIG. 3.
    • Open in new tab
    • Download powerpoint
    FIG. 3.

    Worldwide distribution of different classes of CTX-M β-lactamases (first identified in 1989). (Reprinted from reference 71 by permission of Oxford University Press.)

  • FIG. 4.
    • Open in new tab
    • Download powerpoint
    FIG. 4.

    Dissemination of antibiotics and antibiotic resistance within agriculture, community, hospital, wastewater treatment, and associated environments. (Adapted from reference 49 and reference 83a with permission of the publishers.)

  • FIG. 5.
    • Open in new tab
    • Download powerpoint
    FIG. 5.

    Integron structure and gene capture mechanism. This figure indicates the basic elements of integrons, as found in bacterial genomes. The structure consists of an integrase (Int) with the Pint and PC promoters in the 3′ end of the gene, with its associated cassette attachment or insertion site (attI). The integrase catalyzes the sequential recombination of circularized gene cassettes into the distal attachment site to create an operon-like arrangement (ant1r, ant2r, and so on) of r genes transcribed from the strong PC promoter (132). Three classes of integrons have been identified that differ in their integrase genes.

Tables

  • Figures
  • TABLE 1.

    Modes of action and resistance mechanisms of commonly used antibioticsa

    Antibiotic classExample(s)TargetMode(s) of resistance
    β-LactamsPenicillins (ampicillin), cephalosporins (cephamycin), penems (meropenem), monobactams (aztreonam)Peptidoglycan biosynthesisHydrolysis, efflux, altered target
    AminoglycosidesGentamicin, streptomycin, spectinomycinTranslationPhosphorylation, acetylation, nucleotidylation, efflux, altered target
    GlycopeptidesVancomycin, teicoplaninPeptidoglycan biosynthesisReprogramming peptidoglycan biosynthesis
    TetracyclinesMinocycline, tigecyclineTranslationMonooxygenation, efflux, altered target
    MacrolidesErythromycin, azithromicinTranslationHydrolysis, glycosylation, phosphorylation, efflux, altered target
    LincosamidesClindamycinTranslationNucleotidylation, efflux, altered target
    StreptograminsSynercidTranslationC-O lyase (type B streptogramins), acetylation (type A streptogramins), efflux, altered target
    OxazolidinonesLinezolidTranslationEfflux, altered target
    PhenicolsChloramphenicolTranslationAcetylation, efflux, altered target
    QuinolonesCiprofloxacinDNA replicationAcetylation, efflux, altered target
    PyrimidinesTrimethoprimC1 metabolismEfflux, altered target
    SulfonamidesSulfamethoxazoleC1 metabolismEfflux, altered target
    RifamycinsRifampinTranscriptionADP-ribosylation, efflux, altered target
    LipopeptidesDaptomycinCell membraneAltered target
    Cationic peptidesColistinCell membraneAltered target, efflux
    • ↵ a Adapted from reference 150a with permission of the publisher.

PreviousNext
Back to top
Download PDF
Citation Tools
Origins and Evolution of Antibiotic Resistance
Julian Davies, Dorothy Davies
Microbiology and Molecular Biology Reviews Aug 2010, 74 (3) 417-433; DOI: 10.1128/MMBR.00016-10

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Print

Alerts
Sign In to Email Alerts with your Email Address
Email

Thank you for sharing this Microbiology and Molecular Biology Reviews article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Origins and Evolution of Antibiotic Resistance
(Your Name) has forwarded a page to you from Microbiology and Molecular Biology Reviews
(Your Name) thought you would be interested in this article in Microbiology and Molecular Biology Reviews.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Origins and Evolution of Antibiotic Resistance
Julian Davies, Dorothy Davies
Microbiology and Molecular Biology Reviews Aug 2010, 74 (3) 417-433; DOI: 10.1128/MMBR.00016-10
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Top
  • Article
    • SUMMARY
    • INTRODUCTION
    • A LITTLE ANTIBIOTIC HISTORY
    • SUPERBUGS AND SUPERRESISTANCE
    • MECHANISMS AND ORIGINS OF ANTIBIOTIC RESISTANCE
    • GENETICS OF RESISTANCE
    • ECOLOGICAL ROLES OF ANTIBIOTICS AND ANTIBIOTIC RESISTANCE
    • HOW TO CONTROL OR REDUCE ANTIBIOTIC RESISTANCE DEVELOPMENT
    • CONCLUSIONS
    • ACKNOWLEDGMENTS
    • REFERENCES
  • Figures & Data
  • Info & Metrics
  • PDF

KEYWORDS

Drug Resistance, Microbial
Evolution, Molecular

Related Articles

Cited By...

About

  • About MMBR
  • Editor in Chief
  • Editorial Board
  • For Reviewers
  • For the Media
  • For Librarians
  • For Advertisers
  • Alerts
  • RSS
  • FAQ
  • Permissions
  • Journal Announcements

Authors

  • ASM Author Center
  • Submit a Manuscript
  • Ethics
  • Contact Us

Follow #MMBRJournal

@ASMicrobiology

       

ASM Journals

ASM journals are the most prominent publications in the field, delivering up-to-date and authoritative coverage of both basic and clinical microbiology.

About ASM | Contact Us | Press Room

 

ASM is a member of

Scientific Society Publisher Alliance

 

American Society for Microbiology
1752 N St. NW
Washington, DC 20036
Phone: (202) 737-3600

Copyright © 2021 American Society for Microbiology | Privacy Policy | Website feedback

Print ISSN: 1092-2172; Online ISSN: 1098-5557