Anionic fluoroquinolones as antibacterials against biofilm-producing Pseudomonas aeruginosa

Timothy E. Long; Lexie C. Keding; Demetria D. Lewis; Michael I. Anstead; T. Ryan Withers; Hongwei D. Yu

doi:10.1016/j.bmcl.2016.01.012

Anionic fluoroquinolones as antibacterials against biofilm-producing Pseudomonas aeruginosa

Timothy E. Long, Lexie C. Keding, Demetria D. Lewis, Michael I. Anstead, T. Ryan Withers, Hongwei D. Yu

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

Abstract

Pseudomonas aeruginosa is a common biofilm-forming bacterial pathogen implicated in diseases of the lungs. The extracellular polymeric substances (EPS) of respiratory Pseudomonas biofilms are largely comprised of anionic molecules such as rhamnolipids and alginate that promote a mucoid phenotype. In this Letter, we examine the ability of negatively-charged fluoroquinolones to transverse the EPS and inhibit the growth of mucoid P. aeruginosa. Anionic fluoroquinolones were further compared with standard antibiotics via a novel microdiffusion assay to evaluate drug penetration through pseudomonal alginate and respiratory mucus from a patient with cystic fibrosis.

Original language	English
Pages (from-to)	1305-1309
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	26
Issue number	4
DOIs	https://doi.org/10.1016/j.bmcl.2016.01.012
State	Published - Feb 15 2016

Bibliographical note

Publisher Copyright:
© 2016 Elsevier Ltd. All rights reserved.

Funding

This research was supported in part by the Marshall University School of Pharmacy FRS Grant Program and the Office of Experiential Learning for financial support. Special thanks is also given to NASA West Virginia EPSCoR grant program, the National Center for Research Resources, the National Center for Advancing Translational Sciences, and National Institutes of Health (NIH), through Grant UL1TR000117. HDY is supported by NIH P20GM103434 to the West Virginia IDeA Network for Biomedical Research Excellence, and is the co-founder of Progenesis Technologies, LLC. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Funders	Funder number
Marshall University
NASA West Virginia EPSCoR
Office of Experiential Learning
National Institutes of Health (NIH)
National Institute of General Medical Sciences	P20GM103434
National Center for Research Resources
National Center for Advancing Translational Sciences (NCATS)	UL1TR000117

Keywords

Antibacterial
Biofilm
Fluoroquinolone
Mucoid
Pseudomonas

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2016.01.012

Cite this

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abstract = "Pseudomonas aeruginosa is a common biofilm-forming bacterial pathogen implicated in diseases of the lungs. The extracellular polymeric substances (EPS) of respiratory Pseudomonas biofilms are largely comprised of anionic molecules such as rhamnolipids and alginate that promote a mucoid phenotype. In this Letter, we examine the ability of negatively-charged fluoroquinolones to transverse the EPS and inhibit the growth of mucoid P. aeruginosa. Anionic fluoroquinolones were further compared with standard antibiotics via a novel microdiffusion assay to evaluate drug penetration through pseudomonal alginate and respiratory mucus from a patient with cystic fibrosis.",

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AU - Long, Timothy E.

AU - Keding, Lexie C.

AU - Lewis, Demetria D.

AU - Anstead, Michael I.

AU - Withers, T. Ryan

AU - Yu, Hongwei D.

PY - 2016/2/15

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AB - Pseudomonas aeruginosa is a common biofilm-forming bacterial pathogen implicated in diseases of the lungs. The extracellular polymeric substances (EPS) of respiratory Pseudomonas biofilms are largely comprised of anionic molecules such as rhamnolipids and alginate that promote a mucoid phenotype. In this Letter, we examine the ability of negatively-charged fluoroquinolones to transverse the EPS and inhibit the growth of mucoid P. aeruginosa. Anionic fluoroquinolones were further compared with standard antibiotics via a novel microdiffusion assay to evaluate drug penetration through pseudomonal alginate and respiratory mucus from a patient with cystic fibrosis.

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KW - Biofilm

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KW - Mucoid

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Anionic fluoroquinolones as antibacterials against biofilm-producing Pseudomonas aeruginosa

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

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