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Antibiotic Selection

Antibiotic Selection

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Related Experiment Video

Updated: Jan 4, 2026

Bacterial Inner-membrane Display for Screening a Library of Antibody Fragments

Bacterial Inner-membrane Display for Screening a Library of Antibody Fragments

Published on: October 15, 2016

Dimensionally Enhanced Antibacterial Library Screening.

Navid J Ayon¹, William G Gutheil¹

¹Division of Pharmacology and Pharmaceutical Sciences, School of Pharmacy , University of Missouri-Kansas City , 2464 Charlotte Street , Kansas City , Missouri 64108 , United States.

ACS Chemical Biology

|November 2, 2019

Summary

This summary is machine-generated.

This study enhances antibacterial screening by testing drugs before and after metabolism, and with an antibiotic. This approach identified new compounds and strategies to combat antimicrobial resistance, including drugs effective only after metabolism.

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Area of Science:

Microbiology
Pharmacology
Drug Discovery

Background:

Antimicrobial resistance (AMR) poses a significant global health challenge.
Novel strategies are urgently needed to combat the rise of resistant pathogens.
Methicillin-resistant Staphylococcus aureus (MRSA) is a key target for novel antibacterial development.

Purpose of the Study:

To enhance whole-cell antibacterial screening by increasing dimensionality.
To identify antibacterial agents with improved activity after metabolism.
To discover agents that synergize with existing antibiotics against MRSA.

Main Methods:

Screening of a human liver microsome-metabolized FDA-approved drug library against MRSA.
Comparative analysis of un-metabolized (UM) and pre-metabolized (PM) drug libraries.
Inclusion of a -/+ cefoxitin (Cef) resistance screen to identify synergistic agents.

Main Results:

Five compounds showed significantly enhanced activity post-metabolism.
Four compounds exhibited substantial synergy with cefoxitin.
Capecitabine demonstrated potent antibacterial activity only after metabolism; its metabolites were characterized.
Floxuridine, gemcitabine, novobiocin, and rifaximin showed significant synergy with cefoxitin, with Floxuridine displaying high synergy (FIC = 0.14).

Conclusions:

Dimensionally enhanced screening effectively identifies novel antibacterial agents.
Metabolism-dependent activity and synergistic combinations represent promising strategies against AMR.
This approach aids in discovering new therapeutic options for combating resistant bacterial infections.