Linkage, Mobility, and Selfishness in the MazF Family of Bacterial Toxins: A Snapshot of Bacterial Evolution
Identifieur interne : 000327 ( Main/Exploration ); précédent : 000326; suivant : 000328Linkage, Mobility, and Selfishness in the MazF Family of Bacterial Toxins: A Snapshot of Bacterial Evolution
Auteurs : Nikita Chopra [Inde] ; Abhinandan Pathak [Inde] ; Rakesh Bhatnagar [Inde] ; Sonika Bhatnagar [Inde]Source :
- Genome Biology and Evolution [ 1759-6653 ] ; 2013.
Abstract
Prokaryotic MazF family toxins cooccur with cognate antitoxins having divergent DNA-binding folds and can be of chromosomal or plasmid origin. Sequence similarity search was carried out to identify the Toxin–Antitoxin (TA) operons of MazF family followed by sequence analysis and phylogenetic studies. The genomic DNA upstream of the TA operons was searched for the presence of regulatory motifs. The MazF family toxins showed a conserved hydrophobic pocket in a multibinding site and are present in pathogenic bacteria. The toxins of the MazF family are associated with four main types of cognate antitoxin partners and cluster as a subfamily on the branches of the phylogenetic tree. This indicates that transmission of the entire operon is the dominant mode of inheritance. The plasmid borne TA modules were interspersed between the chromosomal TA modules of the same subfamily, compatible with a frequent interchange of TA genes between the chromosome and the plasmid akin to that observed for antibiotic resistance gens. The split network of the MazF family toxins showed the AbrB-linked toxins as a hub of horizontal gene transfer. Distinct motifs are present in the upstream region of each subfamily. The presence of MazF family TA modules in pathogenic bacteria and identification of a conserved binding pocket are significant for the development of novel antibacterials to disrupt the TA interaction. However, the role of TAs in stress resistance needs to be established. Phylogenetic studies provide insight into the evolution of MazF family TAs and effect on the bacterial genome.
Url:
DOI: 10.1093/gbe/evt175
PubMed: 24265503
PubMed Central: 3879964
Affiliations:
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Snapshot of Bacterial Evolution</title><author><name sortKey="Chopra, Nikita" sort="Chopra, Nikita" uniqKey="Chopra N" first="Nikita" last="Chopra">Nikita Chopra</name><affiliation wicri:level="1"><nlm:aff id="evt175-AFF1">Computational and Structural Biology Laboratory, Division of Biotechnology, Netaji Subhas Institute of Technology, Dwarka, New Delhi, India</nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>Computational and Structural Biology Laboratory, Division of Biotechnology, Netaji Subhas Institute of Technology, Dwarka, New Delhi</wicri:regionArea><wicri:noRegion>New Delhi</wicri:noRegion></affiliation></author><author><name sortKey="Pathak, Abhinandan" sort="Pathak, Abhinandan" uniqKey="Pathak A" first="Abhinandan" last="Pathak">Abhinandan Pathak</name><affiliation wicri:level="1"><nlm:aff id="evt175-AFF1">Computational and Structural Biology Laboratory, Division of Biotechnology, Netaji Subhas Institute of Technology, Dwarka, New Delhi, India</nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>Computational and Structural Biology Laboratory, Division of Biotechnology, Netaji Subhas Institute of Technology, Dwarka, New Delhi</wicri:regionArea><wicri:noRegion>New Delhi</wicri:noRegion></affiliation></author><author><name sortKey="Bhatnagar, Rakesh" sort="Bhatnagar, Rakesh" uniqKey="Bhatnagar R" first="Rakesh" last="Bhatnagar">Rakesh Bhatnagar</name><affiliation wicri:level="1"><nlm:aff id="evt175-AFF2">Laboratory of Molecular Biology and Genetic Engineering, School of Biotechnology, Jawaharlal Nehru University, New Delhi, India</nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>Laboratory of Molecular Biology and Genetic Engineering, School of Biotechnology, Jawaharlal Nehru University, New Delhi</wicri:regionArea><wicri:noRegion>New Delhi</wicri:noRegion></affiliation></author><author><name sortKey="Bhatnagar, Sonika" sort="Bhatnagar, Sonika" uniqKey="Bhatnagar S" first="Sonika" last="Bhatnagar">Sonika Bhatnagar</name><affiliation wicri:level="1"><nlm:aff id="evt175-AFF1">Computational and Structural Biology Laboratory, Division of Biotechnology, Netaji Subhas Institute of Technology, Dwarka, New Delhi, India</nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>Computational and Structural Biology Laboratory, Division of Biotechnology, Netaji Subhas Institute of Technology, Dwarka, New Delhi</wicri:regionArea><wicri:noRegion>New Delhi</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24265503</idno><idno type="pmc">3879964</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3879964</idno><idno type="RBID">PMC:3879964</idno><idno type="doi">10.1093/gbe/evt175</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">000546</idno><idno type="wicri:Area/Pmc/Curation">000546</idno><idno type="wicri:Area/Pmc/Checkpoint">000306</idno><idno type="wicri:Area/Ncbi/Merge">000476</idno><idno type="wicri:Area/Ncbi/Curation">000476</idno><idno type="wicri:Area/Ncbi/Checkpoint">000476</idno><idno type="wicri:Area/Main/Merge">000327</idno><idno type="wicri:Area/Main/Curation">000327</idno><idno type="wicri:Area/Main/Exploration">000327</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Linkage, Mobility, and Selfishness in the MazF Family of Bacterial Toxins: A
Snapshot of Bacterial Evolution</title><author><name sortKey="Chopra, Nikita" sort="Chopra, Nikita" uniqKey="Chopra N" first="Nikita" last="Chopra">Nikita Chopra</name><affiliation wicri:level="1"><nlm:aff id="evt175-AFF1">Computational and Structural Biology Laboratory, Division of Biotechnology, Netaji Subhas Institute of Technology, Dwarka, New Delhi, India</nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>Computational and Structural Biology Laboratory, Division of Biotechnology, Netaji Subhas Institute of Technology, Dwarka, New Delhi</wicri:regionArea><wicri:noRegion>New Delhi</wicri:noRegion></affiliation></author><author><name sortKey="Pathak, Abhinandan" sort="Pathak, Abhinandan" uniqKey="Pathak A" first="Abhinandan" last="Pathak">Abhinandan Pathak</name><affiliation wicri:level="1"><nlm:aff id="evt175-AFF1">Computational and Structural Biology Laboratory, Division of Biotechnology, Netaji Subhas Institute of Technology, Dwarka, New Delhi, India</nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>Computational and Structural Biology Laboratory, Division of Biotechnology, Netaji Subhas Institute of Technology, Dwarka, New Delhi</wicri:regionArea><wicri:noRegion>New Delhi</wicri:noRegion></affiliation></author><author><name sortKey="Bhatnagar, Rakesh" sort="Bhatnagar, Rakesh" uniqKey="Bhatnagar R" first="Rakesh" last="Bhatnagar">Rakesh Bhatnagar</name><affiliation wicri:level="1"><nlm:aff id="evt175-AFF2">Laboratory of Molecular Biology and Genetic Engineering, School of Biotechnology, Jawaharlal Nehru University, New Delhi, India</nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>Laboratory of Molecular Biology and Genetic Engineering, School of Biotechnology, Jawaharlal Nehru University, New Delhi</wicri:regionArea><wicri:noRegion>New Delhi</wicri:noRegion></affiliation></author><author><name sortKey="Bhatnagar, Sonika" sort="Bhatnagar, Sonika" uniqKey="Bhatnagar S" first="Sonika" last="Bhatnagar">Sonika Bhatnagar</name><affiliation wicri:level="1"><nlm:aff id="evt175-AFF1">Computational and Structural Biology Laboratory, Division of Biotechnology, Netaji Subhas Institute of Technology, Dwarka, New Delhi, India</nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>Computational and Structural Biology Laboratory, Division of Biotechnology, Netaji Subhas Institute of Technology, Dwarka, New Delhi</wicri:regionArea><wicri:noRegion>New Delhi</wicri:noRegion></affiliation></author></analytic><series><title level="j">Genome Biology and Evolution</title><idno type="eISSN">1759-6653</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Prokaryotic MazF family toxins cooccur with cognate antitoxins having divergent
DNA-binding folds and can be of chromosomal or plasmid origin. Sequence similarity search
was carried out to identify the Toxin–Antitoxin (TA) operons of MazF family followed
by sequence analysis and phylogenetic studies. The genomic DNA upstream of the TA operons
was searched for the presence of regulatory motifs. The MazF family toxins showed a
conserved hydrophobic pocket in a multibinding site and are present in pathogenic
bacteria. The toxins of the MazF family are associated with four main types of cognate
antitoxin partners and cluster as a subfamily on the branches of the phylogenetic tree.
This indicates that transmission of the entire operon is the dominant mode of inheritance.
The plasmid borne TA modules were interspersed between the chromosomal TA modules of the
same subfamily, compatible with a frequent interchange of TA genes between the chromosome
and the plasmid akin to that observed for antibiotic resistance gens. The split network of
the MazF family toxins showed the AbrB-linked toxins as a hub of horizontal gene transfer.
Distinct motifs are present in the upstream region of each subfamily. The presence of MazF
family TA modules in pathogenic bacteria and identification of a conserved binding pocket
are significant for the development of novel antibacterials to disrupt the TA interaction.
However, the role of TAs in stress resistance needs to be established. Phylogenetic
studies provide insight into the evolution of MazF family TAs and effect on the bacterial
genome.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Abascal, F" uniqKey="Abascal F">F Abascal</name></author><author><name sortKey="Zardoya, R" uniqKey="Zardoya R">R Zardoya</name></author><author><name sortKey="Posada, D" uniqKey="Posada D">D Posada</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Acebo, P" uniqKey="Acebo P">P Acebo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Agarwal, S" uniqKey="Agarwal S">S Agarwal</name></author><author><name sortKey="Mishra, Nk" uniqKey="Mishra N">NK Mishra</name></author><author><name sortKey="Bhatnagar, S" uniqKey="Bhatnagar S">S Bhatnagar</name></author><author><name sortKey="Bhatnagar, R" uniqKey="Bhatnagar R">R Bhatnagar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Altekar, G" uniqKey="Altekar G">G Altekar</name></author><author><name sortKey="Dwarkadas, S" 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Sharp</name></author><author><name sortKey="Kobayashi, H" uniqKey="Kobayashi H">H Kobayashi</name></author><author><name sortKey="Woychik, Na" uniqKey="Woychik N">NA Woychik</name></author><author><name sortKey="Inouye, M" uniqKey="Inouye M">M Inouye</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Inde</li></country></list><tree><country name="Inde"><noRegion><name sortKey="Chopra, Nikita" sort="Chopra, Nikita" uniqKey="Chopra N" first="Nikita" last="Chopra">Nikita Chopra</name></noRegion><name sortKey="Bhatnagar, Rakesh" sort="Bhatnagar, Rakesh" uniqKey="Bhatnagar R" first="Rakesh" last="Bhatnagar">Rakesh Bhatnagar</name><name sortKey="Bhatnagar, Sonika" sort="Bhatnagar, Sonika" uniqKey="Bhatnagar S" first="Sonika" last="Bhatnagar">Sonika Bhatnagar</name><name sortKey="Pathak, Abhinandan" sort="Pathak, Abhinandan" uniqKey="Pathak A" first="Abhinandan" last="Pathak">Abhinandan 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