Review Article: Gentamicin-induced protective effects against T7 bacteriophage infection in Escherichia coli

Abstract

The rapid growth of antibiotic-resistant Escherichia coli globally highlights the need to develop novel antimicrobial treatments including phage therapy or combination therapies. To further understand the combined dynamics between bacteriophage and antibiotics on bacterial survival, past studies have found that E. coli exhibit an increased resistance to T7 bacteriophage when exposed to sub-inhibitory levels of gentamicin, a common antibiotic treatment for E. coli infections. However, the gentamicin-induced mechanism of resistance to phage remains to be elucidated. Here, we review current research and its limitations in regards to this phenomenon and the potential cellular mechanisms by which it occurs, including the gentamicin-induced secretion of outer membrane vesicles, release of soluble lipopolysaccharides, RpoS-mediated stress responses, and increase in capsular polysaccharide formation. We conclude that soluble lipopolysaccharides and RpoS are likely not involved in gentamicin-induced phage resistance, while past studies have not conclusively supported the roles of outer membrane vesicles and capsular polysaccharides. The conflicting evidence for several extracellular mechanisms suggests that it may be useful to consider possible intracellular processes such as ribosomal inhibition or toxin-antitoxin systems. Moreover, limitations and variability in past studies should be addressed in follow-up experiments. With this retrospective, we emphasize the importance of future research in narrowing the scope of potential mechanisms and thus discuss methods to identify the subcellular localization of these protective factors.