The Stringent Response-Regulated sRNA Transcriptome of Borrelia burgdorferi .

The Lyme disease spirochete Borrelia ( Borreliella ) burgdorferi must tolerate nutrient stress to persist in the tick phase of its enzootic life cycle. We previously found that the stringent response mediated by Rel _Bbu globally regulates gene expression to facilitate persistence in the tick vector. Here, we show that Rel _Bbu regulates the expression of a swath of small RNAs (sRNA), affecting 36% of previously identified sRNAs in B. burgdorferi . This is the first sRNA regulatory mechanism identified in any spirochete. Threefold more sRNAs were Rel _Bbu -upregulated than downregulated during nutrient stress and included antisense, intergenic and 5' untranslated region sRNAs. Rel _Bbu -regulated sRNAs associated with genes known to be important for host infection ( bosR and dhhp ) as well as persistence in the tick ( glpF and hk1 ) were identified, suggesting potential mechanisms for post-transcriptional regulation of gene expression.