%0 Journal Article
%T The bacterial defense system MADS interacts with CRISPR-Cas to limit phage infection and escape.
%A Maestri A
%A Pons BJ
%A Pursey E
%A Chong CE
%A Gandon S
%A Custodio R
%A Olina A
%A Agapov A
%A Chisnall MAW
%A Grasso A
%A Paterson S
%A Szczelkun MD
%A Baker KS
%A van Houte S
%A Chevallereau A
%A Westra ER
%J Cell Host Microbe
%V 32
%N 8
%D 2024 Aug 14
%M 39094583
%F 31.316
%R 10.1016/j.chom.2024.07.005
%X The constant arms race between bacteria and their parasites has resulted in a large diversity of bacterial defenses, with many bacteria carrying multiple systems. Here, we report the discovery of a phylogenetically widespread defense system, coined methylation-associated defense system (MADS), which is distributed across gram-positive and gram-negative bacteria. MADS interacts with a CRISPR-Cas system in its native host to provide robust and durable resistance against phages. While phages can acquire epigenetic-mediated resistance against MADS, co-existence of MADS and a CRISPR-Cas system limits escape emergence. MADS comprises eight genes with predicted nuclease, ATPase, kinase, and methyltransferase domains, most of which are essential for either self/non-self discrimination, DNA restriction, or both. The complex genetic architecture of MADS and MADS-like systems, relative to other prokaryotic defenses, points toward highly elaborate mechanisms of sensing infections, defense activation, and/or interference.