**Abstract**

The rapid emergence and dissemination of multidrug-resistant (MDR) bacteria represents a worldwide crisis concerning that humankind is re-entering the 'preantibiotics' era. Before the discovery of antibiotics, bacteriophage therapy was widely enforced to combat bacterial infections. However, the discovery of penicillin in 1940 and other novel antibiotics replaced phage therapy, and they are being used as the first line of defence against pathogenic bacterial infections. Factors such as selective pressure resulted in bacteria becoming insensitive to one or multiple antibiotics, frequently leading to limited treatment options. This prompted a renewal of interest to the phage therapy that remains dubious due to its disadvantages such as host specificity and the development of bacterial resistance against phages. Evolution of bacterial genomes allowed bacteria to acquire vast mechanisms interfering with phage infection such as inhibition of phage adsorption, prevention of phage entry, superinfection exclusion, restriction-modification and abortive infection. Interestingly, phages have developed diverse counterstrategies to circumvent bacterial anti-phage mechanisms including digging for receptors, adapting to new receptors and masking and modifying restriction sites. Understanding the complex dynamics of bacteria-phage interaction is a preliminary step towards designing synthetic phages that can overcome limitations of phage therapy and potentially lead to defeating MDR bacteria.

**Keywords:** bacteria-phage arms race, CRISPR system, anti-CRISPR system, superinfection exclusion (Sie), restriction-modification, abortive infection (Abi)
