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However, they are typically absent from host-associated prokaryotes due to their potential host toxicity. Here, the obligate intracellular bacterium spotted fever group (SFG) rickettsiae, which causes mild to severe human illness, was shown to harbor two <jats:italic>vapBC<\/jats:italic> TA modules. One of the <jats:italic>vapBC<\/jats:italic> modules (<jats:italic>vapBC<\/jats:italic>1) is crucial for <jats:italic>Rickettsia<\/jats:italic> to withstand accumulated host reactive oxidative species (ROS), via induction of bacterial dormancy through cleavage on the anti-codon loop of tRNA<jats:sup>fMet<\/jats:sup>, thereby facilitating intracellular survival and infection in a mouse model. Another <jats:italic>vapBC<\/jats:italic> module (<jats:italic>vapBC<\/jats:italic>2) was found to be activated and toxin exposed to host cytoplasm, contributing to <jats:italic>Rickettsia<\/jats:italic>\u2019s virulence and adaptability in its human host by non-specifically degrading host rRNAs rather than regulating rickettsial growth. Recognition of these rickettsial effectors contributes to understanding the intracellular adaptability and pathogenicity of all host-associated pathogens that harbor TA modules.<\/jats:p>","DOI":"10.1371\/journal.ppat.1013380","type":"journal-article","created":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T17:39:41Z","timestamp":1753897181000},"page":"e1013380","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["VapC toxins promote the pathogenesis of Rickettsia heilongjiangensis by cleaving essential RNAs from both Rickettsia and its 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