Document Type
Journal Article
Publication Date
9-22-2021
Publication Title
Microbiology Spectrum
Department
Biological Science
College/School
Jesse D. Jones College of Science, Engineering and Technology
Abstract
Intervening proteins, or inteins, are mobile genetic elements that are translated within host polypeptides and removed at the protein level by splicing. In protein splicing, a self-mediated reaction removes the intein, leaving a peptide bond in place. While protein splicing can proceed in the absence of external cofactors, several examples of conditional protein splicing (CPS) have emerged. In CPS, the rate and accuracy of splicing are highly dependent on environmental conditions. Because the activity of the intein-containing host protein is compromised prior to splicing and inteins are highly abundant in the microbial world, CPS represents an emerging form of posttranslational regulation that is potentially widespread in microbes. Reactive chlorine species (RCS) are highly potent oxidants encountered by bacteria in a variety of natural environments, including within cells of the mammalian innate immune system. Here, we demonstrate that two naturally occurring RCS, namely, hypochlorous acid (the active compound in bleach) and N-chlorotaurine, can reversibly block splicing of DnaB inteins from Mycobacterium leprae and Mycobacterium smegmatis in vitro. Further, using a reporter that monitors DnaB intein activity within M. smegmatis, we show that DnaB protein splicing is inhibited by RCS in the native host. DnaB, an essential replicative helicase, is the most common intein-housing protein in bacteria. These results add to the growing list of environmental conditions that are relevant to the survival of the intein-containing host and influence protein splicing, as well as suggesting a novel mycobacterial response to RCS. We propose a model in which DnaB splicing, and therefore replication, is paused when these mycobacteria encounter RCS.
Recommended Citation
Lennon, C. W., Wahl, D., Goetz, J. R., & Weinberger 2nd, J. Reactive Chlorine Species Reversibly Inhibit DnaB Protein Splicing in Mycobacteria. Microbiology spectrum, e0030121.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Comments
This is an article published by ASM Journals in Microbiology Spectrum, available at https://doi.org/10.1128/Spectrum.00301-21
Authors' acknowledgements: We are grateful to Marlene Belfort and Michael J. Gray for useful discussions, as well as to Markus Nagl for the gift of NCT. This work was supported by National Institutes of Health/KY INBRE grant P20GM103436, National Institutes of Health grant R15GM143662, and by start-up funds from Murray State University to C.W.L.