Bulgecins as β-Lactam Enhancers Against Multidrug Resistant (MDR) Pseudomonas aeruginosa

Abstract

Antibiotic resistance in non-lactose fermenting pathogens such as Pseudomonas aeruginosa (P. aeruginosa) is increasing, making these clinical pathogens more difficult to treat. Multiple resistance mechanisms exist within P. aeruginosa that affect all classes of antibiotics used in the clinic. New strategies and treatment targets within these MDR pathogens must be exploited. One heretofore untapped target is the family of cell wall enzymes known as lytic transglycosylases (Lts). Lts work in concert with penicillin binding proteins (PBPs) and other cell wall proteins such as amidases and peptidoglycan hydrolases to affect normal cell division, and during stress and programmed cell death. Lts are inhibited by natural products called bulgecins, produced by non-pathogenic Paraburkholderia and Burkholderia spp. New research describing the ability of Lt inhibition to restore susceptibility to β-lactams in MDR P. aeruginosa, as well as the structural biologic basis for the activity of bulgecins will be reviewed. Other targets and applications of bulgecins will also be discussed.