Phage therapy for Clostridioides difficile infection

Abstract

Clostridioides difficile is endemic in the intestinal tract of healthy people. However, it is responsible for many healthcare-associated infections, such as nosocomial diarrhea following antibiotic treatment. Importantly, there have been cases of unsuccessful treatment and relapse related to the emergence of highly virulent strains of C. difficile and resistance to antimicrobial agents. Fecal microbiota transplantation (FMT) is considered an effective therapy for recurrent C. difficile infection. However, its safety is of concern because deaths caused by antibiotic-resistant bacterial infections after FMT were reported. Therefore, the development of effective C. difficile-specific treatments is urgently needed. In this review, we summarize the importance of phage therapy against C. difficile, and describe a novel next-generation phage therapy developed using metagenomic data.

Sterile faecal filtrate transplantation alters phage-microbe dynamics in individuals with metabolic syndrome: a double blind, randomised, placebo-controlled clinical trial assessing efficacy and safety

“…Besides above-mentioned suggestions for future FFT studies, future research should focus on targeting specific bacteria with phages to get a better mechanistic understanding of how bacterial communities are changed upon phage predation and how these changes could affect disease phenotypes. One example of specific phages targeting pathogenic bacteria is the phage cocktail developed to treat recurrent Clostridioides difficile infections 51 . Another interesting target are the Lactobacillaceae that are thought to produce ethanol and thereby contribute to non-alcoholic fatty liver disease (NAFLD) 52 .…”

A Taxonomy-Agnostic Approach to Targeted Microbiome Therapeutics—Leveraging Principles of Systems Biology

“…Bacteriophage viruses (“phages”) were first proposed in the early 20th century, prior to the discovery of antibiotics, as a means of controlling or eliminating infectious bacteria [ 89 , 90 ]. After falling out of favor with the advent of antibiotics, phage therapy is experiencing a renaissance in the treatment of antibiotic-resistant bacterial infections [ 91 ], and now in the field of microbiome therapeutics [ 89 , 91 , 92 ].…”

“…Phages are highly species- and often strain-specific viruses that rapidly replicate within, and then destroy target bacterial cells [ 91 , 92 , 93 ]. Phages endogenous to gut microbiomes are increasingly recognized as important dynamic factors in overall microbiome composition and function; indeed, it has been suggested that some of the microbiome composition changes seen in IBD, for example, are driven at least in part by “blooms” of endogenous phages [ 92 ].…”

A novel truncated CHAP modular endolysin, CHAPSAP26-161, that lysesStaphylococcus aureus,Acinetobacter baumannii,andClostridioides difficile

“…Therefore, there is an urgent need to develop alternative therapeutic strategies to combat these pathogens. Bacteriophages (phages) and their derivative endolysins have emerged as promising candidates in this endeavor (Fujimoto and Uematsu, 2022; Khan and Joshi, 2022; Kortright et al, 2019; Mondal et al, 2021, 2020; Sekiya et al, 2022; Ul Haq et al, 2012). Endolysins, hydrolytic enzymes produced by phages, demonstrate a broad host spectrum and possess the advantages of rapid bacterial cell lysis, low risk of resistance development, and efficacy against biofilms and mucosal surfaces (Abdelrahman et al, 2021; Borysowski et al, 2006; Gondil et al, 2020; Heselpoth et al, 2021; Mirski et al, 2019; Nelson et al, 2012; Schmelcher et al, 2012; Schmelcher and Loessner, 2016).…”