Multiple drug-induced stress responses inhibit formation of Escherichia coli biofilmsстатья
Статья опубликована в высокорейтинговом журнале
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Дата последнего поиска статьи во внешних источниках: 2 декабря 2020 г.
Аннотация:IF= 4.512 (Q1)In most ecosystems, bacteria exist primarily as structured surface-associatedbiofilmsthat can be highly tolerant to antibiotics and thus represent an importanthealth issue. Here, we explored drug repurposing as a strategy to identify new anti-biofilm compounds, screening over 1,000 compounds from the Prestwick ChemicalLibrary of approved drugs for specific activities that prevent biofilm formation byEscherichia coli. Most growth-inhibiting compounds, which include known antibacte-rial but also antiviral and other drugs, also reduced biofilm formation. However, wealso identified several drugs that were biofilm inhibitory at doses where only a weakeffect or no effect on planktonic growth could be observed. The activities of themost specific antibiofilm compounds were further characterized using gene expres-sion analysis, proteomics, and microscopy. We observed that most of these drugsacted by repressing genes responsible for the production of curli, a major compo-nent of theE. colibiofilm matrix. This repression apparently occurred through theinduction of several different stress responses, including DNA and cell wall damage,and homeostasis of divalent cations, demonstrating that biofilm formation can beinhibited through a variety of molecular mechanisms. One tested drug, tyloxapol,did not affect curli expression or cell growth but instead inhibited biofilm formationby suppressing bacterial attachment to the surface.