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In this manuscript, Ting et al. describe three gene clusters - named antagonism resistance clusters (arc1-3) - that are upregulated by the Gac/Rsm danger sensing system and proposed to work as an innate immunity system against antibacterial attacks. This work builds on their previous studies (LeRoux et al., 2015 eLife; LeRoux et al., 2015 J Mol Biol) in which the authors have identified a danger sensing mechanism that bacteria use to sense lysis of neighboring kin cells and activate an offensive T6SS weapon - which was also dependent on the Gac/Rsm regulators.

The arc clusters appear to provide antagonism against specific toxic T6SS effectors, with arc3 cluster being most important to antagonize the toxic effect of the lipase Tle3. 

During interbacterial competition assays between Pseudomonas aeruginosa and Burkholderia thailandensis, arc3 protects P. aeruginosa from detergent-like lysophospholipid toxic products generated by the action of Tle3.

Overall, the article is very interesting and touches on a hot topic in the field: the identification of mechanisms that protect bacteria from T6SS attacks independent of specific immunity proteins.

I have only one major comment:

Is the activation/expression of arc3 cluster regulated by an increase of lysophospholipids in the bacterial membrane? The expression of arc3 genes could be measured in bacteria exposed to extracellular phospholipase from another source or in bacteria expressing the Tle3 toxin from a plasmid. As the authors are claiming arc1-3 genes are innate immune systems, it would be interesting to analyze whether these clusters could be activated without interbacterial contact (downstream of Gac/Rsm) and only by the intracellular detection of the specific danger signal (lysophospholipids). Could they also try adding pure lysophospholipid to mimic the signaling without any bacterial contact?