**Abstract**

The spread of multidrug-resistant pathogens together with the development of fatal cases of infectious microorganisms is on the rise. Therefore, there must be new approaches for combating pathogenic microorganisms, either by overcoming antibiotic resistance or via inhibiting their virulence factors. Several virulence factors extremely increase the antimicrobial resistance of various species of pathogens; as a result, the screening of antivirulence agents has gained more and more attention recently. In this aspect, non-traditional strategies that are considered promising in overcoming virulence and pathogenicity of microorganisms will be discussed including; quorum sensing inhibition, antibiofilm, control of the global regulators, bacteriocins and bacteriophages. Applying these methods could provide innovative approaches for competing microbial resistance and virulence.

**Keywords:** bacterial virulence, resistance, quorum sensing inhibition, global regulators, phage therapy, inhibition of biofilm formation, bacteriocins

## **1. Introduction**

The high incidence of microbial resistance and the spread of multidrug-resistant and pan drug-resistant pathogens have been developed to threaten human mankind. Fortunately, there are upcoming alternative therapeutic approach for eliminating bacterial virulence and host-pathogen interaction [1, 2]. Quorum sensing signals [3, 4] and global regulators represent the main players to control virulence circuits and coordinate host-pathogen interaction [5]. Thus, targeting these regulators provide a promising trend to overcome microbial pathogenicity. Bacterial cells have the ability to grow in matrices of polysaccharides, proteins and DNA forming biofilm [6]. The cell communities inside the biofilm matrices are highly resistant to antibiotics [7]. In this chapter, we will focus on the agents that are known to exhibit antibiofilm assembly including bacteriocins.

Moreover, bacteriophages have specific ability to infect and lyse bacteria [8]. Hence, phage therapy has many potential applications in the treatment of infectious diseases, with high therapeutic index and diminished adverse effects [9, 10]. Inhibitors of quorum sensing signaling, control of the global regulators, and the development of antibiofilm agents will be discussed in detail in this chapter. Additionally, the use of bacteriophages either for eradication of bacterial infections or as an efficient delivery system for antimicrobial agents will be described in this part.
