Abstract
Bacteriophage (phage) therapy, i.e., the use of viruses that infect bacteria as antimicrobial agents, is a promising alternative to conventional antibiotics. Indeed, resistance to antibiotics has become a major public health problem after decades of extensive usage. However, one of the main questions regarding phage therapy is the possible rapid emergence of phage-resistant bacterial variants, which could impede favourable treatment outcomes. Experimental data has shown that phage-resistant variants occurred in up to 80% of studies targeting the intestinal milieu and 50% of studies using sepsis models. Phage-resistant variants have also been observed in human studies, as described in three out of four clinical trials that recorded the emergence of phage resistance. On the other hand, recent animal studies suggest that bacterial mutations that confer phage-resistance may result in fitness costs in the resistant bacterium, which, in turn, could benefit the host. Thus, phage resistance should not be underestimated and efforts should be made to develop methodologies for monitoring and preventing it. Moreover, understanding and taking advantage of the resistance-induced fitness costs in bacterial pathogens is a potentially promising avenue.
Highlights
Antimicrobial resistance is a major public health problem that could possibly cause an estimated10 million mortalities per year by 2050 [1]
Similar observations were made with E. coli, where phage cocktails decreased the frequency of phage-resistance or delayed the emergence of phage-resistant variants [97,98]
Studies suggested that phage–bacterial coevolution was limited to a few rounds of infection cycles
Summary
Antimicrobial resistance is a major public health problem that could possibly cause an estimated. 10 million mortalities per year by 2050 [1] For this reason, novel therapeutic strategies, beside traditional antibiotics, must be rapidly developed. Phages are nature’s most abundant bacterial predators They can be used alone or in combination with antibiotics against difficult-to-treat infections. Bacteria can resist phage attack through different mechanisms, including spontaneous mutations, restriction modification systems, and adaptive immunity via the CRISPR-Cas system [5]. Spontaneous mutations may confer phage resistance by modifying the structure of bacterial surface components that act as phage receptors and that determine phage specificity. Oral administration of phages up to 24 h before V. cholerae challenge reduced colonization of the intestinal tract and prevented cholera-like diarrhoea. Protective effects of phage treatment with lower and delayed mortality 1 or 24 h after bacterial challenge.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
