Engineering a lysin with intrinsic antibacterial activity (LysMK34) with cecropin A enhances its antibacterial properties against < em > Acinetobacter baumannii < /em >

Appl Environ Microbiol. 2021 Oct 20:AEM0151521. doi: 10.1128/AEM.01515-21. Online ahead of print.ABSTRACTBacteriophage-encoded lysins are increasingly reported as alternatives to combat Acinetobacter baumannii infections for which limited therapeutic options are available. Some lysins such as LysMK34 have a C-terminal amphipathic helix allowing them to penetrate the otherwise impermeable outer membrane barrier. Another approach to kill Gram-negative pathogens with lysins relies on fusion of a peptide with outer membrane permeabilizing properties to the lysin. In this work, we aimed to leverage the intrinsic antibacterial activity of LysMK34 by fusing the peptide cecropin A to its N-terminus via a linker of three Ala-Gly repeats, resulting in eLysMK34. The engineered lysin has an improved antibacterial activity compared to the parental lysin LysMK34 in terms of minimum inhibitory concentration (0.45 - 1.2 μM), killing rate and killing extent. eLysMK34 has an at least two-fold increased activity against stationary-phase cells and the bactericidal effect becomes less dependent on the intracellular osmotic pressure. Particularly colistin-resistant strains become highly susceptible to eLysMK34 and enhanced antibacterial activity is observed in complement-deactivated human serum. These observations demonstrate that fusion of a lysin with intrinsic antibacterial activity with a selected outer membrane permeabilizing peptide is a useful strategy to further improve the in vitro antib...
Source: Applied and Environmental Microbiology - Category: Microbiology Authors: Source Type: research