Abstract
ABSTRACTmazEF is a toxin-antitoxin module located on chromosomes of most bacteria. MazF toxins are endoribonucleases antagonized by MazE antitoxins. Previously, we characterized several quorum sensing peptides called "extracellular death factors" (EDFs). When secreted from bacterial cultures, EDFs induce interspecies cell death. EDFs also enhance the endoribonucleolytic activity of Escherichia coli MazF. Mycobacterium tuberculosis carries several mazEF modules. Among them, the endoribonucleolytic activities of MazF proteins mt-1, mt-3, and mt-6 were identified. MazF-mt6 and MazF-mt-3 cleave M. tuberculosis rRNAs. Here we report the in vitro effects of EDFs on the endoribonucleolytic activities of M. tuberculosis MazFs. Escherichia coli EDF (EcEDF) and the three Pseudomonas aeruginosa EDFs (PaEDFs) individually enhance the endoribonucleolytic activities of MazF-mt6 and MazF-mt3 and overcome the inhibitory effect of MazE-mt3 or MazE-mt6 on the endoribonucleolytic activities of the respective toxins. We propose that these EDFs can serve as a basis for a novel class of antibiotics against M. tuberculosis.
Highlights
ABSTRACT mazEF is a toxin-antitoxin module located on chromosomes of most bacteria
We started by studying the effects of each of the several extracellular death factors (EDFs) peptides on the endoribonucleolytic activity of the M. tuberculosis MazF toxin MazF-mt6
Of the many mazEF systems identified in M. tuberculosis so far, three, MazEF-mt6, MazEF-mt3, and MazEF-mt1, have been characterized and their cleaved sites identified [13, 14, 21]
Summary
ABSTRACT mazEF is a toxin-antitoxin module located on chromosomes of most bacteria. MazF toxins are endoribonucleases antagonized by MazE antitoxins. We asked whether each of these different EDFs (including EcEDF, BsEDF, and all three PaEDFs) might enhance the endoribonucleolytic activities of the various M. tuberculosis MazF toxins as we showed in previous studies with E. coli MazF [18, 19]. If so, these EDFs may serve as a basis for a bacteriostatic or even bactericidal effect on M. tuberculosis
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