Heme-Based Oxygen Sensors of Commensal, Symbiotic, and Pathogenic Bacteria




Tuckerman, Jason Robert

Journal Title

Journal ISSN

Volume Title


Content Notes


Direct oxygen sensors are proteins that serve as "on-off switches" to cause reversible and adaptive changes in the activities of other proteins or genes, with great specificity in response to fluctuations in oxygen concentration. The heme-based oxygen sensors are a large class of direct oxygen sensors that feature direct binding of oxygen to a sensory heme-containing domain. This heme-binding region couples to a regulatory domain within the same polypeptide. The types of functionalities controlled by these oxygen-specific switches are diverse, and include the regulation of protein activities, gene expression, and second messenger elaboration. A primary focus of this work was the biochemical characterization of a pair of heme-based oxygen sensors involved in the control of the bacterial second messenger cyclic diguanylic acid (c-di-GMP) in Escherichia coli. We discovered that these enzymes, designated DosC and DosP, serve as a diguanylate cyclase and c-di-GMP phosphodiesterase pair that associate with components of the E. coli RNA degradosome in vivo. Importantly, one member of these degradosomes, PNPase, is a direct, high-affinity target of c-di-GMP. These findings imply that specialized oxygen-sensing degradosomes exist in E. coli. In these oxygen-sensing degradosomes cellular oxygen levels regulate PNPase processing of specific RNA transcripts via c-di-GMP. A secondary focus of this work was the characterization of a novel two-component system in M. tuberculosis involved in the non-replicating persistent phase of this bacterium in a typical TB infection. Here, the activities of two heme-containing histidine kinases, DosT and DevS, were discovered to be inhibited specifically by oxygen. As DosT and DevS are the primary regulators of the dormancy survival regulator (DosR/DevR) transcription factor, these results contributed a molecular explanation for the numerous observations linking oxygen and DevR to the dormancy phenotype of M. tuberculosis seen both in vitro and in vivo.

General Notes

Table of Contents


Related URI