The mechanism of bacterial defense system DdmDE from Lactobacillus casei

Dear Editor,

Prokaryotes have evolved a multitude of defense systems that confer immunity against invasive mobile genetic elements.^1,2,3,4,5 A two-gene DNA defense module DdmDE system is found in Vibrionaceae and Lactobacillaceae family and imposes fitness advantages to the bacteria by eliminating invasive plasmids.⁶ DdmD encodes a fusion protein comprising an N-terminal superfamily 2 helicase and a C-terminal PD-(D/E)XK superfamily nuclease, while DdmE is a putative prokaryotic Argonaute-like protein that frequently engages in bacterial immunity. Although recent studies described the function and structure of DdmDE from Vibrio cholerae,^6,7,8,9 the mechanistic basis by which the DdmDE system detects and degrades plasmids is not fully understood. In particular, the process by which DdmD dimer dissociates and how the DNA is captured by the nuclease domain for degradation remain elusive.

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