Inhibiting bacterial secretion systems in the fight against antibiotic resistance

Elizabeth Boudaher, Carrie L. Shaffer

Research output: Contribution to journalReview articlepeer-review

11 Scopus citations

Abstract

Antimicrobial resistance is a mounting global health crisis that threatens a resurgence of life-threatening bacterial infections. Despite intensive drug discovery efforts, the rate of antimicrobial resistance outpaces the discovery of new antibiotic agents. One of the major mechanisms driving the rapid propagation of antibiotic resistance is bacterial conjugation mediated by the versatile type IV secretion system (T4SS). The search for therapeutic compounds that prevent the spread of antibiotic resistance via T4SS-dependent mechanisms has identified several promising molecular scaffolds that disrupt resistance determinant dissemination. In this brief review, we highlight the progress and potential of conjugation inhibitors and anti-virulence compounds that target diverse T4SS machineries. These studies provide a solid foundation for the future development of potent, dual-purpose molecular scaffolds that can be used as biochemical tools to probe type IV secretion mechanisms and target bacterial conjugation in clinical settings to prevent the dissemination of antibiotic resistance throughout microbial populations.

Original languageEnglish
Pages (from-to)682-692
Number of pages11
JournalMedChemComm
Volume10
Issue number5
DOIs
StatePublished - 2019

Bibliographical note

Funding Information:
We thank all investigators working in the field of T4SS biology and the development of T4SS inhibitors. We apologize if their work is not cited due to the scope of the review presenting the most recent advances in T4SS inhibitor development. We thank Jamie K. Norris for assistance with figure design and production. Our work on T4SS mechanisms and bacterial antibiotic resistance is supported by startup funds from the University of Kentucky College of Food, Agriculture, and Environment (to CLS) and pilot awards from the University of Kentucky Center for Molecular Medicine (NIH P30 GM110787 to CLS).

Publisher Copyright:
© 2019 The Royal Society of Chemistry.

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry

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