Authors: Shaleen B Korch Vandana Malhotra Heidi Contreras Josephine E ClarkCurtiss
Publish Date: 2015/10/28
Volume: 53, Issue: 11, Pages: 783-795
Abstract
Toxinantitoxin TA genes are ubiquitous among bacteria and are associated with persistence and dormancy Following exposure to unfavorable environmental stimuli several species Escherichia coli Staphylococcus aureus Myxococcus xanthus employ toxin proteins such as RelE and MazF to downregulate growth or initiate cell death Mycobacterium tuberculosis possesses three Rel TA modules Rel Mtb RelBE Mtb RelFG Mtb and RelJK Mtb Rv1246cRv1247c Rv2865Rv2866 and Rv3357Rv3358 respectively which inhibit mycobacterial growth when the toxin gene relE relG relK is expressed independently of the antitoxin gene relB relF relJ In the present study we examined the in vivo mechanism of the RelE Mtb toxin protein the impact of RelE Mtb on M tuberculosis physiology and the environmental conditions that regulate all three rel Mtb modules RelE Mtb negatively impacts growth and the structural integrity of the mycobacterial envelope generating cells with aberrant forms that are prone to extensive aggregation At a time coincident with growth defects RelE Mtb mediates mRNA degradation in vivo resulting in significant changes to the proteome We establish that rel Mtb modules are stress responsive as all three operons are transcriptionally activated following mycobacterial exposure to oxidative stress or nitrogenlimiting growth environments Here we present evidence that the rel Mtb toxinantitoxin family is stressresponsive and through the degradation of mRNA the RelE Mtb toxin influences the growth proteome and morphology of mycobacterial cells
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