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F Mohamad,1,* Raghad R Alzahrani,2,3,* Ahlam Alsaadi,1 Bahauddeen M Alrfaei,4 Alaa Eldeen B Yassin,5 Manal M Alkhulaifi,3 Majed Halwani2 1Infectious Diseases Research Department, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia; 2Nanomedicine Department, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia; 3Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia; 4Stem Cells and Regenerative Medicine, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia; 5College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia*These authors contributed equally to this workCorrespondence: Majed Halwani, P.O. Box 3660, Mail Code 1515 (KAIMRC), Riyadh, 11481, Tel +966 (11) 429-4433, Fax +966 (11) 429-4440, Email majed.halwani@gmail.com; halawanima@ngha.med.sa Manal M Alkhulaifi, P.O. Box 55670, Riyadh, 11544, Tel +966 (11) 805-1685, Email manalk@ksu.edu.saAbstract: The continuous emergence of multidrug-resistant pathogens evoked the development of innovative approaches targeting virulence factors unique to their pathogenic cascade. These approaches aimed to explore anti-virulence or anti-infective therapies. There are evident concerns regarding the bacterial ability to create a superstructure, the biofilm. Biofilm formation is a crucial virulence factor causing difficult-to-treat, localized, and systemic infections. The microenvironments of bacterial biofilm reduce the efficacy of antibiotics and evade the host’s immunity. Producing a biofilm is not limited to a specific group of bacteria; however, Pseudomonas aeruginosa, Acinetobacter baumannii, and Staphylococcus aureus biofilms are exemplary models. This review discusses biofilm formation as a virulence factor and the link to antimicrobial resistance. In addition, it explores insights into innovative multi-targeted approaches and their physiological mechanisms to combat biofilms, including natural compounds, phages, antimicrobial photodynamic therapy (aPDT), CRISPR-Cas gene editing, and nano-mediated techniques.Keywords: bacterial biofilms, natural compounds, phages, aPDT, CRISPR, nanotechnology |