TY - JOUR
T1 - Toxin-antitoxin gene pairs found in Tn3 family transposons appear to be an integral part of the transposition module
AU - Lima-Mendez, Gipsi
AU - Alvarenga, Danillo Oliveira
AU - Ross, Karen
AU - Hallet, Bernard
AU - Van Melderen, Laurence
AU - Varani, Alessandro M.
AU - Chandler, Michael
N1 - Funding Information:
This work was primarily funded by the Global Emerging Infections Surveillance (GEIS) and Response System (P0020_18_WR; awarded to Michael Chandler and Patrick McGann). We thank Martin Boocock for providing information concerning the res sites and Jian Zhang (Protein Information Resource PIR, Georgetown University), Hongzhan Huang (Protein Information Resource PIR, University of Delaware), and Cathy Wu (Protein Information Resource, PIR Georgetown University and University of Delaware) for providing essential expert assistance and both conceptual and practical support. Invaluable contributions were made by Erik Snesrud and Patrick McGann (Walter Reed Army Institute of Research).
Publisher Copyright:
© 2020 Lima-Mendez et al.
PY - 2020/3/1
Y1 - 2020/3/1
N2 - Much of the diversity of prokaryotic genomes is contributed by the tightly controlled recombination activity of transposons (Tns). The Tn3 family is argu-ably one of the most widespread transposon families. Members carry a large range of passenger genes incorporated into their structures. Family members undergo rep-licative transposition using a DDE transposase to generate a cointegrate structure which is then resolved by site-specific recombination between specific DNA sequences (res) on each of the two Tn copies in the cointegrate. These sites also carry promoters controlling expression of the recombinase and transposase. We report here that a number of Tn3 members encode a type II toxin-antitoxin (TA) system, typically composed of a stable toxin and a labile antitoxin that binds the toxin and inhibits its lethal activity. This system serves to improve plasmid maintenance in a bacterial population and, until recently, was believed to be associated with bacterial persistence. At least six different TA gene pairs are associated with various Tn3 members. Our data suggest that several independent acquisition events have oc-curred. In contrast to most Tn3 family passenger genes, which are generally located away from the transposition module, the TA gene pairs abut the res site upstream of the resolvase genes. Although their role when part of Tn3 family transposons is un-clear, this finding suggests a potential role for the embedded TA in stabilizing the associated transposon with the possibility that TA expression is coupled to expression of transposase and resolvase during the transposition process itself. IMPORTANCE Transposable elements (TEs) are important in genetic diversification due to their recombination properties and their ability to promote horizontal gene transfer. Over the last decades, much effort has been made to understand TE transposition mechanisms and their impact on prokaryotic genomes. For example, the Tn3 family is ubiquitous in bacteria, molding their host genomes by the paste-and-copy mechanism. In addition to the transposition module, Tn3 members often carry additional passenger genes (e.g., conferring antibiotic or heavy metal resistance and virulence), and three were previously known to carry a toxin-antitoxin (TA) system often associated with plas-mid maintenance; however, the role of TA systems within the Tn3 family is unknown. The genetic context of TA systems in Tn3 members suggests that they may play a regulatory role in ensuring stable invasion of these Tns during transposition.
AB - Much of the diversity of prokaryotic genomes is contributed by the tightly controlled recombination activity of transposons (Tns). The Tn3 family is argu-ably one of the most widespread transposon families. Members carry a large range of passenger genes incorporated into their structures. Family members undergo rep-licative transposition using a DDE transposase to generate a cointegrate structure which is then resolved by site-specific recombination between specific DNA sequences (res) on each of the two Tn copies in the cointegrate. These sites also carry promoters controlling expression of the recombinase and transposase. We report here that a number of Tn3 members encode a type II toxin-antitoxin (TA) system, typically composed of a stable toxin and a labile antitoxin that binds the toxin and inhibits its lethal activity. This system serves to improve plasmid maintenance in a bacterial population and, until recently, was believed to be associated with bacterial persistence. At least six different TA gene pairs are associated with various Tn3 members. Our data suggest that several independent acquisition events have oc-curred. In contrast to most Tn3 family passenger genes, which are generally located away from the transposition module, the TA gene pairs abut the res site upstream of the resolvase genes. Although their role when part of Tn3 family transposons is un-clear, this finding suggests a potential role for the embedded TA in stabilizing the associated transposon with the possibility that TA expression is coupled to expression of transposase and resolvase during the transposition process itself. IMPORTANCE Transposable elements (TEs) are important in genetic diversification due to their recombination properties and their ability to promote horizontal gene transfer. Over the last decades, much effort has been made to understand TE transposition mechanisms and their impact on prokaryotic genomes. For example, the Tn3 family is ubiquitous in bacteria, molding their host genomes by the paste-and-copy mechanism. In addition to the transposition module, Tn3 members often carry additional passenger genes (e.g., conferring antibiotic or heavy metal resistance and virulence), and three were previously known to carry a toxin-antitoxin (TA) system often associated with plas-mid maintenance; however, the role of TA systems within the Tn3 family is unknown. The genetic context of TA systems in Tn3 members suggests that they may play a regulatory role in ensuring stable invasion of these Tns during transposition.
KW - Antitoxin
KW - Tn3 family
KW - Toxin
KW - Transposition
UR - http://www.scopus.com/inward/record.url?scp=85082731807&partnerID=8YFLogxK
U2 - 10.1128/mBio.00452-20
DO - 10.1128/mBio.00452-20
M3 - Article
C2 - 32234815
AN - SCOPUS:85082731807
SN - 2161-2129
VL - 11
JO - mBio
JF - mBio
IS - 2
M1 - e00452-20
ER -