Abstract
Biofilms are well-organised communities of microbes embedded in a self-produced extracellular matrix (e.g., curli amyloid fibers) and are associated with chronic infections. Therefore, development of anti-biofilm drugs is important to combat with these infections. Previously, we found that flavonol Myricetin inhibits curli-dependent biofilm formation by Escherichia coli (IC50 = 46.2 μM). In this study, we tested activities of seven Myricetin-derivatives to inhibit biofilm formation by E. coli K-12 in liquid culture. Among them, only Epigallocatechin gallate (EGCG), a major catechin in green tea, inhibited biofilm formation of K-12 (IC50 = 5.9 μM) more efficiently than Myricetin. Transmission electron microscopy and immunoblotting analyses demonstrated that EGCG prevented curli production by suppressing the expression of curli-related proteins. Quantitative RT-PCR analysis revealed that the transcripts of csgA, csgB, and csgD were significantly reduced in the presence of EGCG. Interestingly, the cellular level of RpoS, a stationary-phase specific alternative sigma factor, was reduced in the presence of EGCG, whereas the rpoS transcript was not affected. Antibiotic-chase experiments and genetic analyses revealed that EGCG accelerated RpoS degradation by ATP-dependent protease ClpXP in combination with its adaptor RssB. Collectively, these results provide significant insights into the development of drugs to treat chronic biofilm-associated infections.
Highlights
Biofilms are well-organised microbial communities that attach to biotic or abiotic surfaces
Cellulose is one of the important biofilm matrix components in E. coli, some of E. coli K-12 strains including BW25113 have been reported not to produce cellulose due to a point mutation in BcsQ, an essential component of the E. coli cellulose biosynthesis apparatus that localizes at the bacterial cell pole[31,32,33]
We demonstrated that the Myricetin-derivative Epigallocatechin gallate (EGCG) effectively inhibited curli biosynthesis and biofilm formation by laboratory and clinically isolated E. coli strains (Figs 2–4)
Summary
Biofilms are well-organised microbial communities that attach to biotic or abiotic surfaces. Curli are major extracellular surface amyloid fibers produced by many Enterobacteriaceae such as Escherichia coli, Salmonella enterica, and Citrobactor spp[7,8,9]. The major and minor subunits of curli are CsgA and CsgB, respectively These proteins are synthesised in the cytoplasm, transported to the periplasm via the Sec www.nature.com/scientificreports/. Transcriptional regulation of curli biogenesis is a complex process involving many other factors, which is reviewed elsewhere[22]. These regulators could be potential drug targets to combat curli-dependent biofilms. More effective and/or less cytotoxic anti-biofilm compounds should be developed
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