Poly (acetyl, arginyl) glucosamine disrupts Pseudomonas aeruginosa biofilms and enhances bacterial clearance in a rat lung infection model

Bryan A. Garcia; Melissa S. McDaniel; Allister J. Loughran; J. Dixon Johns; Vidya Narayanaswamy; Courtney Fernandez Petty; Susan E. Birket; Shenda M. Baker; Roxanna Barnaby; Bruce A. Stanton; Jeremy B. Foote; Steven M. Rowe; W. Edward Swords

doi:10.1099/mic.0.001121

Poly (acetyl, arginyl) glucosamine disrupts Pseudomonas aeruginosa biofilms and enhances bacterial clearance in a rat lung infection model

Bryan A. Garcia^1,2,3, Melissa S. McDaniel^3,4, Allister J. Loughran^5,6, J. Dixon Johns^2,3, Vidya Narayanaswamy⁵, Courtney Fernandez Petty², Susan E. Birket^2,3,4,7, Shenda M. Baker^5,8, Roxanna Barnaby⁹, Bruce A. Stanton⁹, Jeremy B. Foote¹⁰, Steven M. Rowe^2,3,4,7 and W. Edward Swords^2,3,4
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Affiliations: ¹ Department of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Medical University of South Carolina, Charleston, SC, USA ² Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA ³ Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA ⁴ Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama, USA ⁵ Synedgen, Inc., Claremont, CA, USA ⁶ St Jude Children’s Research Hospital, Memphis, TN, USA ⁷ Department of Cell Developmental and Integrative Physiology, University of Alabama at Birmingham, Birmingham, Alabama, USA ⁸ Synspira Therapeutics, Inc., Framingham, MA, USA ⁹ Dartmouth Cystic Fibrosis Research Center, New Hanover, NH, USA ¹⁰ Comparative Pathology Laboratory, at University of Alabama at Birmingham, Birmingham, Alabama, USA
*Correspondence: W. Edward Swords, [email protected]
Published: 25 January 2022 https://doi.org/10.1099/mic.0.001121

Abstract

Pseudomonas aeruginosa is a common opportunistic pathogen that can cause chronic infections in multiple disease states, including respiratory infections in patients with cystic fibrosis (CF) and non-CF bronchiectasis. Like many opportunists, P. aeruginosa forms multicellular biofilm communities that are widely thought to be an important determinant of bacterial persistence and resistance to antimicrobials and host immune effectors during chronic/recurrent infections. Poly (acetyl, arginyl) glucosamine (PAAG) is a glycopolymer that has antimicrobial activity against a broad range of bacterial species, and also has mucolytic activity, which can normalize the rheological properties of cystic fibrosis mucus. In this study, we sought to evaluate the effect of PAAG on P. aeruginosa bacteria within biofilms in vitro, and in the context of experimental pulmonary infection in a rodent infection model. PAAG treatment caused significant bactericidal activity against P. aeruginosa biofilms, and a reduction in the total biomass of preformed P. aeruginosa biofilms on abiotic surfaces, as well as on the surface of immortalized cystic fibrosis human bronchial epithelial cells. Studies of membrane integrity indicated that PAAG causes changes to P. aeruginosa cell morphology and dysregulates membrane polarity. PAAG treatment reduced infection and consequent tissue inflammation in experimental P. aeruginosa rat infections. Based on these findings we conclude that PAAG represents a novel means to combat P. aeruginosa infection, and may warrant further evaluation as a therapeutic.

Received: 28/05/2021
Accepted: 29/10/2021
Published Online: 25/01/2022

Keyword(s): biofilm , cystic fibrosis , mucus and Pseudomonas aeruginosa

Funding

This study was supported by the:

National Heart, Lung, and Blood Institute (Award R35 HL135816)
- Principle Award Recipient: StevenM. Rowe
National Institute of Diabetes and Digestive and Kidney Diseases (Award P30DK072482)
- Principle Award Recipient: StevenM. Rowe
Cystic Fibrosis Foundation (Award CFF SWORDS20G0)
- Principle Award Recipient: Edward Edward SwordsW.
Cystic Fibrosis Foundation (Award CFF SWORDS1810)
- Principle Award Recipient: Edward Edward SwordsW.
Cystic Fibrosis Foundation (Award RDP R15RO)
- Principle Award Recipient: StevenM. Rowe
Synedgen
- Principle Award Recipient: StevenM. Rowe

This is an open-access article distributed under the terms of the Creative Commons Attribution License.

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/content/journal/micro/10.1099/mic.0.001121

Poly (acetyl, arginyl) glucosamine disrupts Pseudomonas aeruginosa biofilms and enhances bacterial clearance in a rat lung infection model

Microbiology 168, 001121 (2022); https://doi.org/10.1099/mic.0.001121

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Microbiology

Volume 168, Issue 1

Research Article

Open Access

Poly (acetyl, arginyl) glucosamine disrupts Pseudomonas aeruginosa biofilms and enhances bacterial clearance in a rat lung infection model

Abstract

Funding

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