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Multiple phage resistance systems inhibit infection via SIR2-dependent NAD+ depletion

Nat Microbiol. 2022-10; 
Jeremy Garb, Anna Lopatina, Aude Bernheim, Mindaugas Zaremba, Virginijus Siksnys, Sarah Melamed, Azita Leavitt, Adi Millman, Gil Amitai, Rotem Sorek
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GenParts™ DNA Fragments … Genome analyses of hybrid phages enabled us to pinpoint the exact phage proteins that … A cloning shuttle vector for large fragments was constructed by Genscript Corp. This vector was … Get A Quote

摘要

Defence-associated sirtuins (DSRs) comprise a family of proteins that defend bacteria from phage infection via an unknown mechanism. These proteins are common in bacteria and harbour an N-terminal sirtuin (SIR2) domain. In this study we report that DSR proteins degrade nicotinamide adenine dinucleotide (NAD+) during infection, depleting the cell of this essential molecule and aborting phage propagation. Our data show that one of these proteins, DSR2, directly identifies phage tail tube proteins and then becomes an active NADase in Bacillus subtilis. Using a phage mating methodology that promotes genetic exchange between pairs of DSR2-sensitive and DSR2-resistant phages, we further show that some phag... More

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