Evolutionary Rationale for Phages as Complements of Antibiotics

Antibiotic-resistant bacterial infections are a major concern to public health. Phage therapy has been proposed as a promising alternative to antibiotics, but an increasing number of studies suggest that both of these antimicrobial agents in combination are more effective in controlling pathogenic bacteria than either alone. We advocate the use of phages in combination with antibiotics and present the evolutionary basis for our claim. In addition, we identify compelling challenges for the realistic application of phage–antibiotic combined therapy. Antibiotic-resistant bacterial infections are a major concern to public health. Phage therapy has been proposed as a promising alternative to antibiotics, but an increasing number of studies suggest that both of these antimicrobial agents in combination are more effective in controlling pathogenic bacteria than either alone. We advocate the use of phages in combination with antibiotics and present the evolutionary basis for our claim. In addition, we identify compelling challenges for the realistic application of phage–antibiotic combined therapy. The efficacy of new and old antibiotics could be preserved if combined with phages. Positive interactions have been observed between antibiotics and lytic phages in controlling bacterial pathogens both in vitro and in vivo. Phage–antibiotic combinations are capable of targeting multidrug-resistant bacteria but their underlying mechanisms remain to be discovered. Evolutionary biology provides a framework for understanding the interactions between antimicrobial agents and the successful management of bacterial pathogens, their resistance, and their virulence. Video Abstract https://www.cell.com/cms/asset/f4d1b750-0d2c-48be-8d04-ee92c399bb9f/mmc1.mp4 Loading ... (mp4, 42.57 MB) Download video The efficacy of new and old antibiotics could be preserved if combined with phages. Positive interactions have been observed between antibiotics and lytic phages in controlling bacterial pathogens both in vitro and in vivo. Phage–antibiotic combinations are capable of targeting multidrug-resistant bacteria but their underlying mechanisms remain to be discovered. Evolutionary biology provides a framework for understanding the interactions between antimicrobial agents and the successful management of bacterial pathogens, their resistance, and their virulence. group of microorganisms that adhere to each other, frequently embedded within a self-produced extracellular matrix. occurs when one of two or more species competing for the same resource or exposed to the same stressor disappears, thereby allowing the remaining competitor(s) to utilize the resource and repopulate the community. major component of the outer membrane of Gram-negative bacteria. Large molecules consisting of a lipid and a polysaccharide composed of an O-antigen, expressed as an outer core and inner core joined by a covalent bond. a phenomenon whereby antibiotics stimulate the production of phages by bacterial hosts under certain conditions. dormant variants of regular cells that form stochastically in microbial populations and are highly tolerant to antibiotics. proteins that cross a cellular membrane in bacteria and act as a pore through which molecules such as small metabolites or antibiotics can diffuse. the monitoring of the environment for other bacteria resulting in the coordination of gene expression. general bacterial stress response pathway that is induced by DNA damage caused by a wide range of stressors, including antibiotics. Effects of its activation include increased bacterial survival and antibiotic resistance, prophage activation, or the horizontal transfer of virulence factors.