Year: 2022
Type: article
Abstract: Multidrug-resistant (MDR) Enterococcus faecalis are major causes of hospital-acquired infections. Numerous clinical strains of E. faecalis harbor a large pathogenicity island that encodes enterococcal surface protein (Esp), which is suggested to promote biofilm production and virulence, but this remains controversial. To resolve this issue, we characterized the Esp N-terminal region, the portion implicated in biofilm production. Small angle X-ray scattering indicated that the N-terminal region had a globular head, which consisted of two DEv-Ig domains as visualized by X-ray crystallography, followed by an extended tail. The N-terminal region was not required for biofilm production but instead significantly strengthened biofilms against mechanical or degradative disruption, greatly increasing retention of Enterococcus within biofilms. Biofilm strengthening required low pH, which resulted in Esp unfolding, aggregating, and forming amyloid-like structures. The pH threshold for biofilm strengthening depended on protein stability. A truncated fragment of the first DEv-Ig domain, plausibly generated by a host protease, was the least stable and sufficient to strengthen biofilms at pH ≤ 5.0, while the entire N-terminal region and intact Esp on the enterococcal surface was more stable and required a pH ≤ 4.3. These results suggested a virulence role of Esp in strengthening enterococcal biofilms in acidic abiotic or host environments.
Source: PLoS Pathogens
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,655
Funders: U.S. Department of Energy, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Office of Science, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Center for Research Resources, Argonne National Laboratory
Awards: G102163711, G107546177, Evasion of host immunity by the M protein, TAS::89 0222::TAS-NEW: INORGANIC CONTROL OF BIOLOGICAL SELF-ASSEMBLY: ENGINEERING NOVEL BIOLOGICAL ARCHITECTURES AND REDOX-ACTIVE PROTEIN ASSEMBLIES;, G1286236842, G1313983767, G1414775356, Protein-Glycan Interaction Resource at the National Center for Functional Glycomics (NCFG), G1505794299, G1664757510, G1767990418, G1816284028, Cell and Molecular Genetics Training Program, G2101401529, G2287611682, G262962599, G2638771445, Acquisition of a High Resolution TOF Mass Spectrometer, G2887060908, G3075337988, G3083819904, Towards Accurate Protein Structure Predictions with SAXS Technology (TAPESTRY), G3257500209, G334911014, G340565428, G3435343525, G365575497, G382641700, Mechanisms of the M protein in group A Streptococcus virulence, G4149293343, G419881185, G42916606, G4501827968, G498139845, G5106849484, G5607048534, G6652958823, G6802451166, G6848031779, G6918803902, G7368700025, G7912248388, G805243471, G8229677252, National Center for Functional Glycomics, G8682639235, G9000054807, G9000263589, G9000349690, ALS Efficiently Networking Advanced Beam Line Experiments (ALS-ENABLE), G969889393, G993149817
OpenAlex ID: W4295706187