Microbial Control and Microbiome Engineering Using Polyvalent Bacteriophages

J. Mathieu, P. Yu, and P. Alvarez
Rice University, Texas, United States

Keywords: bacteriophage, antibiotic resistance, biodecontamination, pathogen, microbiome

The increasing prevalence of antibiotic-resistant bacteria (ARB) has led to warnings of a “post-antibiotic era”, where current antibiotics are of reduced efficacy, and the barriers to developing novel antibiotics too great. Thus, there is an enormous impetus to reduce antibiotic use and find sustainable alternatives. Bacteriophages appear to be promising alternatives to antibiotics, though the strict host-specificity displayed by most bacteriophages has hindered their widespread adoption. Yet contrary to the common belief that bacteriophages are highly specific, we recently developed methods to isolate wide host-range (polyvalent) phages, and have found them to be more prevalent than previously appreciated, and highly effective agents for microbial control. Advantages of polyvalent bacteriophages relative to narrower host-range bacteriophages include decreased complexity of bacteriophage cocktails, higher titers in environments with multiple hosts (e.g., human gut), decreased phage decay rates, better propagation within biofilms, and safer, more economical production. Our research has demonstrated polyvalent bacteriophages to be 10- to 100-fold more effective than narrower host-range bacteriophages at controlling target bacteria in various natural and built environments. Advantages over antibiotics include self-replication, the ability to evolve, and tunable specificity. Potential applications include the treatment of ARB infections, bio-decontamination, microbiome engineering, and control of problematic environmental bacteria.