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Abstract
Biofilm formation is a critical step in the pathogenesis of difficult-to-treat Gram-positive bacterial infections. We identified that YajC, a conserved membrane protein in bacteria, plays a role in biofilm formation of the clinically relevant Enterococcus faecium strain E1162. Deletion of yajC conferred significantly impaired biofilm formation in vitro and was attenuated in a rat endocarditis model. Mass spectrometry analysis of supernatants of washed ΔyajC cells revealed increased amounts in cytoplasmic and cell-surface-located proteins, including biofilm-associated proteins, suggesting that proteins on the surface of the yajC mutant are only loosely attached. In Streptococcus mutans YajC has been identified in complex with proteins of two cotranslational membrane protein-insertion pathways; the signal recognition particle (SRP)-SecYEG-YajC-YidC1 and the SRP-YajC-YidC2 pathway, but its function is unknown. In S. mutans mutation of yidC1 and yidC2 resulted in impaired protein insertion in the cell membrane and secretion in the supernatant. The E. faecium genome contains all homologous genes encoding for the cotranslational membrane protein-insertion pathways. By combining the studies in S. mutans and E. faecium, we propose that YajC is involved in the stabilization of the SRP-SecYEG-YajC-YidC1 and SRP-YajC-Yid2 pathway or plays a role in retaining proteins for proper docking to the YidC insertases for translocation in and over the membrane.
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1 Department of Medical Microbiology, University Medical Center Utrecht , PO box 85500, 3584 CX Utrecht , the Netherlands
2 College of Agriculture and Forestry, Linyi University , Building 60, Yujingwan, Linyi City, Shandong Province, 276000 , China
3 Centre for Infectious Disease Control (Clb), National Institute for Public Health and the Environment (RIVM) , Antonie van Leeuwenhoeklaan 9, 3721 MA Bilthoven , the Netherlands
4 Laboratory of Biochemistry, Wageningen University , PO box 8128, 6700 ET Wageningen , the Netherlands
5 Institute of Microbiology and Infection, College of Medical and Dental Sciences, University of Birmingham , Birmingham B15 2TT , United Kingdom
6 Division of Pediatric Infectious Diseases, Hauner Children's Hospital, Ludwig-Maximilian Universität München , Lindwurmstr. 4, 80337 Munich , Germany