Multi-target regulators represent a largely untapped area for metabolic engineering and anti-bacterial development. These regulators are complex to characterize because they often act at multiple levels, affecting proteins, transcripts and metabolites. Therefore, single omics experiments cannot profile their underlying targets and mechanisms. In this work, we used an Integrative FourD omics approach (INFO) that consists of collecting and analyzing systems data throughout multiple time points, using multiple genetic backgrounds, and multiple omics approaches (transcriptomics, proteomics and high throughput sequencing crosslinking immunoprecipitation) to evaluate simultaneous changes in gene expression after imposing an environmental stress that accentuates the regulatory features of a network. Using this approach, we profiled the targets and potential regulatory mechanisms of a global regulatory system, the well-studied carbon storage regulatory (Csr) system of Escherichia coli, which is widespread among bacteria. Using 126 sets of proteomics and transcriptomics data, we identified 136 potential direct CsrA targets, including 50 novel ones, categorized their behaviors into distinct regulatory patterns, and performed in vivo fluorescence-based follow up experiments. The results of this work validate 17 novel mRNAs as authentic direct CsrA targets and demonstrate a generalizable strategy to integrate multiple lines of omics data to identify a core pool of regulator targets.

We present a case of a 54-year-old gentleman with a history of hypertension and chronic HIV who presented with fever and epigastric pain, found to have elevated troponin-I levels and diffuse ST-segement elevations on ECG without clinical evidence of ischemia concerning for myopericarditis. Initial laboratory findings also included thrombocytopenia and elevated aminotransferases as well as computed tomography imaging revealing splenic infarcts. Given plausible exposure to ticks, this led to the eventual diagnosis of anaplasmosis confirmed on PCR assay. Cardiac MRI images confirmed myocardial involvement, which resolved with antibiotic treatment. While rare, cardiac involvement is possible sequelae of anaplasmosis infection as illustrated by this case.

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