TY - JOUR
T1 - Toxins of toxin/antitoxin systems are inactivated primarily through promoter mutations
AU - Fernandez-Garcia, L.
AU - Kim, J. S.
AU - Tomas, M.
AU - Wood, T. K.
N1 - Publisher Copyright:
© 2019 The Society for Applied Microbiology
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Aims: Given the extreme toxicity of some of the toxins of toxin-antitoxin (TA) systems, we were curious how the cell silences toxins, if the antitoxin is inactivated or independent toxins are obtained via horizontal gene transfer. Methods and Results: Growth curves of Escherichia coli K12 BW25113 harbouring plasmid pCA24N to produce RalR, MqsR, GhoT or Hha toxins, showed toxin inactivation after 3 h. Sequencing plasmids from these cultures revealed toxin inactivation occurred primarily due to consistent deletions in the promoter. The lack of mutation in the structural genes was corroborated by a bioinformatics analysis of 1000 E. coli genomes which showed both conservation and little variability in the four toxin genes. For those strains that lacked a mutation in the plasmid, single nucleotide polymorphism analysis was performed to identify that chromosomal mutations iraM and mhpR inactivate the toxins GhoT and MqsR/GhoT respectively. Conclusion: We find that the RalR (type I), MqsR (type II), GhoT (type V) and Hha (type VII) toxins are inactivated primarily by a mutation that inactivates the toxin promoter or via the chromosomal mutations iraM and mhpR. Significance and Impact of the Study: This study demonstrates toxins of TA systems may be inactivated by mutations that primarily affect the toxin gene promoter instead of the toxin structural gene.
AB - Aims: Given the extreme toxicity of some of the toxins of toxin-antitoxin (TA) systems, we were curious how the cell silences toxins, if the antitoxin is inactivated or independent toxins are obtained via horizontal gene transfer. Methods and Results: Growth curves of Escherichia coli K12 BW25113 harbouring plasmid pCA24N to produce RalR, MqsR, GhoT or Hha toxins, showed toxin inactivation after 3 h. Sequencing plasmids from these cultures revealed toxin inactivation occurred primarily due to consistent deletions in the promoter. The lack of mutation in the structural genes was corroborated by a bioinformatics analysis of 1000 E. coli genomes which showed both conservation and little variability in the four toxin genes. For those strains that lacked a mutation in the plasmid, single nucleotide polymorphism analysis was performed to identify that chromosomal mutations iraM and mhpR inactivate the toxins GhoT and MqsR/GhoT respectively. Conclusion: We find that the RalR (type I), MqsR (type II), GhoT (type V) and Hha (type VII) toxins are inactivated primarily by a mutation that inactivates the toxin promoter or via the chromosomal mutations iraM and mhpR. Significance and Impact of the Study: This study demonstrates toxins of TA systems may be inactivated by mutations that primarily affect the toxin gene promoter instead of the toxin structural gene.
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U2 - 10.1111/jam.14414
DO - 10.1111/jam.14414
M3 - Article
C2 - 31429177
AN - SCOPUS:85071499497
SN - 1364-5072
VL - 127
SP - 1859
EP - 1868
JO - Journal of Applied Microbiology
JF - Journal of Applied Microbiology
IS - 6
ER -