Abstract
Microbial biofilms are the cause of persistent infections associated with various medical implants and distinct body sites such as the urinary tract, lungs, and wounds. Compared with their free living counterparts, bacteria in biofilms display a highly increased resistance to immune system activities and antibiotic treatment. Therefore, biofilm infections are difficult or impossible to treat with our current armory of antibiotics. The challenges associated with biofilm infections have urged researchers to pursue a better understanding of the molecular mechanisms that are involved in the formation and dispersal of biofilms, and this has led to the identification of several steps that could be targeted in order to eradicate these challenging infections. Here we describe mechanisms that are involved in the regulation of biofilm development in Pseudomonas aeruginosa, Escherichia coli, and Acinetobacter baumannii, and provide examples of chemical compounds that have been developed to specifically inhibit these processes. These compounds include (i) pilicides and curlicides which inhibit the initial steps of biofilm formation by E. coli; (ii) compounds that interfere with c-di-GMP signaling in P. aeruginosa and E. coli; and (iii) compounds that inhibit quorum-sensing in P. aeruginosa and A. baumannii. In cases where compound series have a defined molecular target, we focus on elucidating structure activity relationship (SAR) trends within the particular compound series.
Highlights
During the last two decades it has been realized that the biofilm mode of growth is the predominant life-mode of most bacterial species (Flemming and Wuertz, 2019)
We provide examples of chemical compounds that have been developed to inhibit specific biofilm formation processes. These compounds include i) pilicides and curlicides which inhibit the initial steps of biofilm formation by E. coli; ii) compounds that interfere with c-di-GMP signaling in P. aeruginosa and E. coli; and iii) compounds that inhibit quorum sensing in P. aeruginosa and A. baumannii
We describe pilicides and curlicides which inhibit the initial steps of biofilm formation by E. coli, and compounds that interfere with c-di-GMP signaling in P. aeruginosa and E. coli, as well as compounds that inhibit Quorum sensing (QS) in P. aeruginosa and A. baumannii
Summary
During the last two decades it has been realized that the biofilm mode of growth is the predominant life-mode of most bacterial species (Flemming and Wuertz, 2019). The problematic infections caused by biofilms have urged researchers to study the molecular mechanisms underlying biofilm formation and biofilm dispersal. This has led to the identification of distinct molecules and mechanisms that could serve as target for novel anti-biofilm drugs. We describe our current knowledge of the molecular mechanisms involved in biofilm development for the Gram negative opportunistic pathogens Pseudomonas aeruginosa, Escherichia coli, and Acinetobacter baumannii, which are all causing problematic biofilm infections. We provide examples of chemical compounds that have been developed to inhibit specific biofilm formation processes These compounds include i) pilicides and curlicides which inhibit the initial steps of biofilm formation by E. coli; ii) compounds that interfere with c-di-GMP signaling in P. aeruginosa and E. coli; and iii) compounds that inhibit quorum sensing in P. aeruginosa and A. baumannii
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