Antibiotic Adjuvant Activity Revealed in a Photoaffinity Approach to Determine the Molecular Target of Antipyocyanin Compounds

Overview

Journal ACS Infect Dis

Specialties Infectious Diseases
Microbiology
Pharmacology

Date 2021 Feb 15

PMID 33587590

Authors

Zinan Zhang

Dominic Ortega

Anthony Rush

Lauren R Blankenship

Zi Jun Cheng

Rebecca E Moore

Minh L N Tran

Lucero G Sandoval

Kareem Aboulhosn

Seiichiro Watanabe

Kendra S Cortez

David H Perlman

Martin F Semmelhack

Laura C Miller Conrad

Affiliations

Soon will be listed here.

Abstract

Infections with are a looming threat to public health. New treatment strategies are needed to combat this pathogen, for example, by blocking the production of virulence factors like pyocyanin. A photoaffinity analogue of an antipyocyanin compound was developed to interrogate the inhibitor's molecular mechanism of action. While we sought to develop antivirulence inhibitors, the proteomics results suggested that the compounds had antibiotic adjuvant activity. Unexpectedly, we found that these compounds amplify the bactericidal activity of colistin, a well-characterized antibiotic, suggesting they may represent a first-in-class antibiotic adjuvant therapy. Analogues have the potential not only to widen the therapeutic index of cationic antimicrobial peptides like colistin, but also to be effective against colistin-resistant strains, strengthening our arsenal to combat infections.

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