Abstract
Antibiotics have had a profound impact on human society by enabling the eradication of otherwise deadly infections. Unfortunately, antibiotic use and overuse has led to the rapid spread of acquired antibiotic resistance, creating a major threat to public health. Novel therapeutic agents called bacteriophage endolysins (lysins) provide a solution to the worldwide epidemic of antibiotic resistance. Lysins are a class of enzymes produced by bacteriophages during the lytic cycle, which are capable of cleaving bonds in the bacterial cell wall, resulting in the death of the bacteria within seconds after contact. Through evolutionary selection of the phage progeny to be released and spread, these lysins target different critical components in the cell wall, making resistance to these molecules orders of magnitude less likely than conventional antibiotics. Such properties make lysins uniquely suitable for the treatment of multidrug resistant bacterial pathogens. Lysins, either naturally occurring or engineered, have the potential of being developed into fast-acting, narrow-spectrum, biofilm-disrupting antimicrobials that act synergistically with standard of care antibiotics. This review focuses on newly discovered classes of Gram-negative lysins with emphasis on prototypical enzymes that have been evaluated for efficacy against the major antibiotic resistant organisms causing nosocomial infections.
Highlights
The discovery of penicillin in 1928 at St
As Antimicrobial resistance (AMR) continues to grow as a global health threat, novel and nontraditional therapeutic agents are urgently needed to fill the gap that traditional small molecule antibiotics are failing to meet
Common lysin characteristics such as a narrow spectrum activity, coupled with potent and rapid bactericidal activity against specific bacterial pathogens, anti-biofilm activity, a low propensity for developing resistance, and synergy with standard-of-care antibiotics, make these Gram-negative lysins ideal candidates to take on the challenge of AMR
Summary
The discovery of penicillin in 1928 at St. Mary’s Hospital in London changed the course of infectious disease treatment and increased patient survival [1]. Antimicrobial resistance (AMR) is a major threat to global health and human development, and is not merely a medical problem, and an economic and social problem [5]. Each year in the U.S alone at least two million people are infected with antibiotic-resistant bacteria, and at least 35,000 of these patients die [6]. Multidrug-resistant (MDR) Gram-negative infections are widely recognized as one of the greatest areas of unmet medical need, carbapenem-resistant pathogens such as Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa, which are on the rise among hospitalized patients [5,7,8]. It is predicted that by 2050 more than 10 million people will die per year due to AMR infections unless action is taken today to spur development of novel and nontraditional antibiotics [9].
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