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Title: Demolishing the great wall of biofilms in Gram‐negative bacteria : to disrupt or disperse?
Authors: Yu, M 
Chua, SL 
Issue Date: May-2020
Source: Medicinal research reviews, May 2020, v. 40, no. 3, p. 1103-1116
Abstract: Bacterial infections lead to high morbidity and mortality globally. While current therapies against bacteria often employ antibiotics, most bacterial pathogens can form biofilms and prevent effective treatment of infections. Biofilm cells can aggregate and encased themselves in a self‐secreted protective exopolymeric matrix, to reduce the penetration by antibiotics. Biofilm formation is mediated by c‐di‐GMP signaling, the ubiquitous secondary messenger in bacteria. Synthesis of c‐di‐GMP by diguanylate cyclases leads to biofilm formation via the loss of motility, increased surface attachment, and production of biofilm matrix, whereas c‐di‐GMP degradation by phosphodiesterases causes biofilm dispersal to new sites via increased bacterial motility and matrix breakdown. The highly variable nature of biofilm development and antimicrobial tolerance imposes tremendous challenges in conventional antimicrobial therapies, indicating an imperative need to develop anti‐biofilm drugs against biofilm infections. In this review, we focus on two main emergent approaches—active dispersal and disruption. While both approaches aim to demolish biofilms, we will discuss their fundamental differences and associated methods. Active dispersal of biofilms involves signaling the bacterial cells to leave the biofilm, where resident cells ditch their sessile lifestyle, gain motility and self‐degrade their matrix. Biofilm disruption leads to direct matrix degradation that forcibly releases embedded biofilm cells. Without the protection of biofilm matrix, released bacterial cells are highly exposed to antimicrobials, leading to their eradication in biofilm infections. Understanding the advantages and disadvantages of both approaches will allow optimized utility with antimicrobials in clinical settings.
Keywords: Antimicrobial treatment
Chronic infections
Publisher: John Wiley & Sons
Journal: Medicinal research reviews 
EISSN: 0198-6325
DOI: 10.1002/med.21647
Rights: © 2019 Wiley Periodicals, Inc
This is the peer reviewed version of the following article: Yu, M, Lin Chua, S. Demolishing the great wall of biofilms in Gram-negative bacteria: To disrupt or disperse? Med Res Rev. 2020; 40: 1103–1116, which has been published in final form at This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.
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