Resistance Development to Bacteriophages Occurring during Bacteriophage Therapy

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.

Interaction of phages, bacteria, and the human immune system: Evolutionary changes in phage therapy

“…Nevertheless, an increased phage resistance causes a reduced competitive bacterial fitness to the environment . As phage resistance requires many resources, mutation that result in phage resistance can cause other mutations related to bacterial fitness . Hall et al reported that bacteria possessing a broad range of phage resistance had a lower fitness as compared with the phage‐susceptible bacterial population .…”

“…Reduction of fitness includes reduced growth rate and loss of important surface features necessary for bacterial virulence . Thus, phage resistance is suggested to be unfavourable to bacteria themselves and in contrary, phage‐driven adaptation might be beneficial for the bacteria . Furthermore, phage resistance in bacteria is believed to be a temporary process.…”

A brief history of periodontics in the United States of America: Pioneers and thought‐leaders of the past, and current challenges

“…Nevertheless, bacteriophages are easily transmitted from person to person, demonstrated by data showing that substantial numbers of gut and oral bacteriophages are shared amongst genetically unrelated, cohabitating individuals . Finally, therapeutic use of bacteriophages to attack pathogens selectively within biofilm communities has been suggested . This approach is not without its problems because in early bacteriophage therapy trials, the emergence of pathogens resistant to bacteriophage attacks has been demonstrated .…”

Digest: Lab versus nature: Disease resistance evolution differs between environments*

“…). Resistance to phages commonly evolves when bacteria are cultured in vitro , but few studies have investigated phage resistance evolution within natural bacterial hosts such as plants or animals (Oechslin ).…”

“…vitro, but few studies have investigated phage resistance evolution within natural bacterial hosts such as plants or animals (Oechslin 2018).…”