PT - JOURNAL ARTICLE AU - Manash C. Das AU - Antu Das AU - Sourabh Samaddar AU - Akshay Vishnu Daware AU - Chinmoy Ghosh AU - Shukdeb Acharjee AU - Padmani Sandhu AU - Junaid Jibran Jawed AU - Utpal C. De AU - Subrata Majumdar AU - Sujoy K. Das Gupta AU - Yusuf Akhter AU - Surajit Bhattacharjee TI - Vitexin alters <em>Staphylococcus aureus</em> surface hydrophobicity to interfere with biofilm formation AID - 10.1101/301473 DP - 2018 Jan 01 TA - bioRxiv PG - 301473 4099 - http://biorxiv.org/content/early/2018/04/14/301473.short 4100 - http://biorxiv.org/content/early/2018/04/14/301473.full AB - Bacterial surface hydrophobicity is one of the determinant biophysical parameters of bacterial aggregation for being networked to form biofilm. Phytoconstituents like vitexin have long been in use for their antibacterial effect. The present work is aimed to characterise the effect of vitexin on S. aureus surface hydrophobicity and corresponding aggregation to form biofilm. We have found that vitexin shows minimum inhibitory concentration at 252 μg/ml against S. aureus. Vitexin reduces cell surface hydrophobicity and membrane permeability at sub-MIC dose of 126 μg/ml. The in silico binding analysis showed higher binding affinity of vitexin with surface proteins of S. aureus. Down regulation of dltA, icaAB and reduction in membrane potential under sub-MIC dose of vitexin, explains reduced S. aureus surface hydrophobicity. Vitexin has substantially reduced the intracellular adhesion of planktonic cells to form biofilm through interference of EPS formation, motility and subsequent execution of virulence. This was supported by the observation that vitexin down regulates the expression of icaAB and agrAC genes of S. aureus. In addition, vitexin also found to potentiate antibiofilm activity of sub-MIC dose of gentamicin and azithromycin. Furthermore, CFU count, histological examination of mouse tissue and immunomodulatory study justifies the in vivo protective effect of vitexin from S. aureus biofilm associated infection. Finally it can be inferred that, vitexin has the ability to modulate S. aureus cell surface hydrophobicity which can further interfere biofilm formation of the bacteria.Importance There has been substantial information known about role of bacterial surface hydrophobicity during attachment of single planktonic bacterial cells to any surface and the subsequent development of mature biofilm. This study presents the effect of flavone phytoconstituent vitexin on modulation of cell surface hydrophobicity in reducing formation of biofilm. Our findings also highlight the ability of vitexin in reducing in vivo S. aureus biofilm which will eventually outcompete the corresponding in vitro antibiofilm effect. Synergistic effect of vitexin on azithromycin and gentamicin point to a regime where development of drug tolerance may be addressed. Our findings explore one probable way of overcoming drug tolerance through application of vitexin in addressing the issue of S. aureus biofilm through modulation of cell surface hydrophobicity.