PT - JOURNAL ARTICLE AU - Paramita Sarkar AU - Amy Switzer AU - Christine Peters AU - Joe Pogliano AU - Sivaramesh Wigneshweraraj TI - Phenotypic consequences of RNA polymerase dysregulation in <em>Escherichia coli</em> AID - 10.1101/150581 DP - 2017 Jan 01 TA - bioRxiv PG - 150581 4099 - http://biorxiv.org/content/early/2017/06/18/150581.short 4100 - http://biorxiv.org/content/early/2017/06/18/150581.full AB - Many bacterial adaptive responses to changes in growth conditions due to biotic and abiotic factors involve reprogramming of gene expression at the transcription level. The bacterial RNA polymerase (RNAP), which catalyzes transcription, can thus be considered as the major mediator of cellular adaptive strategies. But how do bacteria respond if a stress factor directly compromises the activity of the RNAP? We used a phage-derived small protein to specifically perturb bacterial RNAP activity in exponentially growing Escherichia coli. Using cytological profiling, tracking RNAP behavior at single-molecule level and transcriptome analysis, we reveal that adaptation to conditions that directly perturb bacterial RNAP performance can result in a biphasic growth behavior and thereby confer the ‘adapted’ bacterial cells an enhanced ability to tolerate diverse antibacterial stresses. The results imply that while synthetic transcriptional rewiring may confer bacteria with the intended desirable properties, such approaches may also collaterally allow them to acquire undesirable traits.