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Important Complexities of the Antivirulence Target Paradigm: A Novel Ostensibly Resistance-Avoiding Approach for

Thomas A Russo1, Brad Spellberg2, James R Johnson3

  • 1Veterans Administration Western New York Healthcare System Department of Medicine Department of Microbiology and Immunology Witebsky Center for Microbial Pathogenesis, University at Buffalo-State University of New York, New York.

The Journal of Infectious Diseases
|November 14, 2015
PubMed

Insights

Antivirulence therapies may unexpectedly drive resistance in non-infection sites like the environment or microbiome. Further research is needed to assess resistance development in diverse bacterial niches beyond the infection site.

Area of Science:

  • Microbiology
  • Pharmacology
  • Evolutionary Biology

Background:

  • Antivirulence therapies aim to reduce bacterial harm without killing bacteria, theoretically minimizing resistance.
  • This approach assumes resistance primarily develops at the infection site.

Purpose of the Study:

  • To investigate the potential for antivirulence therapy to select for resistant bacterial strains in non-infection sites.
  • To evaluate if drug targets confer a fitness advantage in diverse ecological niches.

Main Methods:

  • The study proposes a framework for evaluating resistance selection.
  • It emphasizes the need for in vivo studies examining off-target resistance, including within the microbiome.

Main Results:

  • Selection for resistant strains is more probable in colonization sites or the environment post-excretion.
  • Data on bacterial fitness in drug-exposed niches beyond infection sites are crucial.

Conclusions:

  • Current assumptions about antivirulence therapy minimizing resistance may be incomplete.
  • Comprehensive assessment of resistance risk requires evaluating diverse niches and off-target effects.
Keywords:
antimicrobial resistanceantimicrobial targetsantivirulence therapymicrobiomeresistance selectionvirulence factors

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