Developments and opportunities of bacteriophage lytic proteins for therapeutics against gram-negative pathogens

The globally increasing antimicrobial resistance levels urge for the introduction of novel classes of antimicrobials. In this regard, enzyme-based antibiotics (or enzybiotics) derived from phage lytic proteins represent a promising strategy. These enzymes kill bacteria through peptidoglycan degradation followed by osmotic lysis and come along with significant advantages such as a rapid bactericidal effect, a novel mode of action and a low probability of resistance development. They have been progressed significantly on the route for clinical application to treat infections caused by Gram-positive bacteria. The latter have a thick but easily accessible peptidoglycan layer. Gram-negative bacteria have been for long a no go zone for enzybiotics due to their protective outer membrane, principally excluding access to the thin peptidoglycan layer. This view has shifted drastically, particularly driven by the lack of remaining therapeutic options for infections caused by Gram-negatives. Diverse strategies grouped in three classes (phage lytic proteins with a natural intrinsic antibacterial activity, combination strategies with physical or chemical means and protein engineering) have been proposed and developed in the last decade, ranging from the conceptual to the preclinical level, and will be discussed in this chapter.

ISBN:9781913652524

Publication year:2020

Accessibility:Closed