Antibiotics are treasures and many times lifesaving agents. They can retain this stature only if they are handled correctly and prescribed appropriately. Emergence of resistant strains is the consequence of wholesale abuse of antibiotic drugs, lack of awareness about antibiotic resistance among the individuals and patient's ignorance on antibiotic treatments. To address antimicrobial drugs resistance issues, collaborations of various disciplines and modernization is required for the development of novel therapeutics and antimicrobial strategies.

Mechanisms developed by host bacteria to digest extrinsic (Phage) DNA: Restriction modification system comprised of enzymes such as endonuclease which recognize and cleave specific sequence in phage DNA and methyltransferase which protect host DNA due to specific methylation or development of adaptive immune response through interfering with CRISPR-cas system.

Phage infection resistance strategy: Over millions of years bacteria have coevolved with viruses (Bacteriophages), ergo they have adapted numerous resistance mechanisms.a)Phage adsorption blocking one of the major resistance mechanisms is achieved by surface modification of bacterial cell via receptor concealment, downregulation or conformation changes [66].

Cocktail of phages are developed against different species of bacteria present within the biofilms and predominant in purulent infections. P. aeruginosa lung infection in mouse and sepsis in Galleria mellonella (wax moth) model was successfully treated with cocktail of six phages

Many in vitro and in vivo studies have demonstrated that phage therapy has been used for the successful treatment of antibiotic resistant pulmonary infections (Pneumonia, and cystic fibrosis), gastrointestinal infections, and topical and wound infections.

. The classifications are based upon the evaluation of diverse phage properties such as genome composition, morphology, host range, sequence similarity and pathogenicity (Table 1).

Bacteriophages are viruses, the most abundant organisms and the natural predators of bacteria. They are self-replicating, obligatory intracellular parasites and inert biochemically in extracellular environment. They control the biosynthetic machinery of bacterial host and behest them to produce different viral proteins. They are considered as particles outside the host cell containing nucleic acid (DNA or RNA) which encode necessary information required for their replication. They are primordial ubiquitous organisms found in diverse environment such as soil, water, feces etc [4,5]. Typically, bacteriophage morphology exhibit well defined three-dimensional structure. The genetic material is enclosed in an icosahedral protein capsid head, a tail (spiral contractile sheath surrounding a core pipe and a baseplate with tail fibers) and surface receptor proteins responsible to recognize specific surface molecules on the host bacterium [5].

Thus, phage therapy applications have noted significant progress in broader clinical practices. In fact, phages can be used for different applications ranging from human antibiotherapy to environment disinfection. This review discusses the therapeutic use of bacteriophages as novel antimicrobial agents to vanquish antimicrobial resistance and several modern approaches to phage therapy,

Antimicrobial resistance is a global health problem and one of the leading concerns in healthcare sector. Bacteriophages are antibacterial agents ubiquitous in nature. With increase in antibiotic resistance, use of bacteriophages as therapeutics has become resurgent in recent times. This review focuses on the recent developments in phage therapy and its applications with respect to human infections, animal, food and environment. Moreover, use of phage proteins, bioengineered bacteriophages, and phage derived vaccines is also highlighted. Additionally, the limitations and challenges with regard to implementation of phage therapy, host safety and immune responses are also reviewed in this article.

CRISPR-Cas delivery into target cells has multiple approaches. However, its delivery as an antimicrobial targeting antimicrobial-resistant bacterial cells is limited.

This was the first study of non-viral delivery of the CRISPR system as an antimicrobial agent for treating MDR bacteria. Rodrigues et al. used Enterococcus faecalis with a CRISPR-Cas-encoding conjugative plasmid to reduce antibiotic resistance in enterococcal populations [31]. Citorik et al. used conjugative delivery and phagemid delivery to target blaSHV-18 or blaNDM-1 [32].4.2. Phage-delivered CRISPR-Cas antimicrobials

In gene editing through CRISPR-Cas9, crRNA [same as single guide RNA (sgRNA)] and Cas9 protein need to be active in target cells. The target DNA is recognised by sgRNA and is bound by the cleavage complex.

Phage therapy through intravesical administration has been used to treat urinary tract infections in patients scheduled to undergo transurethral resection of the prostate

Recently, several RCTs on phage therapy for bacterial infections in humans have been conducted and published (Table 1), including phase II RCTs on the topical administration of phage therapy that have gained significant attention [10], [11]. Wright et al. used a topical (ear drop) phage preparation for chronic otitis due to antibiotic-resistant Pseudomonas aeruginosa infection and their results have revealed improved outcomes compared with those following placebo administration [10]. Jault et al. used a topical phage cocktail on a P. aeruginosa-infected burn wound.

Bacteriophages (phages) are a category of viruses capable of infecting bacteria. Phages were first documented in 1915 and were named bacteriophages in 1917 [1], [2]. Attempts to use phages to treat infectious diseases have been made but were generally abandoned after the 1940s owing to their difficulty in use, poor efficacy and the increasing use of antibiotics [3].

Multidrug-resistant (MDR) bacterial infections in humans are increasing worldwide. The global spread of antimicrobial resistance poses a considerable threat to human health. Phage therapy is a promising approach to combat MDR bacteria. An increasing number of reports have been published on phage therapy and the successful application of antibacterials derived using this method. Additionally, the CRISPR-Cas system has been used to develop antimicrobials with bactericidal effects in vivo. The CRISPR-Cas system can be delivered into target bacteria in various ways, with phage-based vectors being reported as an effective method. In this review, we briefly summarise the results of randomised control trials on bacteriophage therapy.