AJOU Central Library Repository: Unveiling the mechanism of bactericidal activity of a cecropin A-fused endolysin LNT103

Unveiling the mechanism of bactericidal activity of a cecropin A-fused endolysin LNT103

Keyword: Gram-negative bacteria; endolysin; lipopolysaccharide; membrane permeability

Alternative Abstract: Bacteriophages encode endolysins at the end of their lytic cycle to degrade the peptidoglycan layer of the host bacterium, leading to release of progeny phages. In virtue of the bacteriolytic activity, endolysins have been explored as an alternative antibacterial agent. However, the outer membrane present in Gram-negative bacteria obstructs the access of exogenous endolysins to the peptidoglycan lying beneath the outermost membranous structure. In order to overcome the restriction of intrinsic endolysins against Gram-negative bacteria, an endolysin encoded by Pseudomonas aeruginosa phage PBPA90 was engineered by substituting the 15 amino acids (mtPA90) and further by fusing the antimicrobial peptide cecropin A to its N-terminus (LNT103). Cecropin A of LNT103 improved the interaction with lipopolysaccharides (LPS) and accelerated the disruption of both bacterial membranes including the outer membrane and the inner membrane. LNT103 did not compromise the integrity of LPS structure. However, an LPS mutant strain with an altered lipid A structure was more susceptible to both endolysins of mtPA90 and LNT103, suggesting that the integrity of lipid A is important to obstruct endolysin penetration into bacterial membrane. This study revealed that an endolysin fused with cecropin A could not only degrade its intrinsic target peptidoglycan layers but also destabilize both bacterial membranes, leading to faster inactivation of Gram-negative bacteria.

Appears in Collections:: Graduate School of Ajou University > Department of Molecular Science and Technology > 3. Theses(Master)

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