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Gyrase Inhibition by Toxin‐Antitoxin Modules
Author(s) -
Bourne Christina R,
White John C,
Dabadi Shivani,
Muthuramalingam Meenakumari
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.777.14
Subject(s) - dna gyrase , biology , genetics , antitoxin , ribosome , translation (biology) , dna , toxin , microbiology and biotechnology , computational biology , gene , rna , escherichia coli , messenger rna
Toxin‐Antitoxin (TA) modules are interacting cytosolic protein pairs found in most prokaryotes that can mediate metabolic adaptation by interacting with essential cellular machinery. TA modules are organized into families with highly similar structures yet poorly conserved sequences. Among these, the RelE/ParE superfamily has conserved protein folds but disparate cellular functions. Interactions of RelE‐type toxins with the ribosome, resulting in translational inhibition, have been well characterized. In contrast, the interactions of ParE toxins with their target, DNA gyrase, have remained elusive. The objective of this study was to determine the potency of individual ParE toxin proteins with respect to gyrase inhibition. This was determined by changes in cell morphology when the toxins were over‐expressed, and directly using in vitro inhibition assays. Through these studies we have identified a severely truncated ParE toxin in Agrobacterium tumefaciens that maintains an ability to inhibit DNA gyrase. We have also discovered a sub‐family member within this organism that closely matches the E. coli YoeB translation‐inhibiting toxin, however, it effectively inhibits DNA gyrase. Continuing studies are evaluating the propensity of RelE/ParE superfamily members to interact with DNA gyrase. Among over‐expressed ParE toxins, characteristic patterns of filamentatous cell morphology are consistent with phylogenetic sequence analyses. In conclusion, these results unexpectedly revealed that selected members of this superfamily can carry out overlapping functions. Ongoing studies are pursuing shared sequence features dictating these resulting phenotypes, as well as the structural interactions between the toxins and their cellular target. Support or Funding Information This research was supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20GM103640.