Identification and characterization of acetyltransferase-type toxin-antitoxin locus in Klebsiella pneumoniae

作者: Hongliang Qian , Qingqing Yao , Cui Tai , Zixin Deng , Jianhua Gan

DOI: 10.1111/MMI.13934

关键词:

摘要: A type II toxin-antitoxin (TA) system, in which the toxin contains a Gcn5-related N-acetyltransferase (GNAT) domain, has been characterized recently. GNAT acetylates aminoacyl-tRNA and blocks protein translation. It is abolished by cognate antitoxin that ribbon-helix-helix (RHH) domain. Here, we present an experimental demonstration of interaction GNAT-RHH complex with TA promoter DNA. First, locus kacAT was found Klebsiella pneumoniae HS11286, strain resistant to multiple antibiotics. Overexpression KacT halted cell growth resulted persister formation. The crystal structure also indicated typical acetyltransferase toxin. Co-expression KacA neutralized toxicity. Expression bicistronic up-regulated during antibiotic stress. Finally, formed heterohexamer interacted DNA, resulting negative autoregulation transcription. N-terminus region accounted for specific binding palindromic sequence on operator whereas its C-terminus essential inactivation These results provide important insight into regulation family system.

参考文章(50)
Kenn Gerdes, Susanne K. Christensen, Anders Løbner-Olesen, Prokaryotic toxin-antitoxin stress response loci. Nature Reviews Microbiology. ,vol. 3, pp. 371- 382 ,(2005) , 10.1038/NRMICRO1147
Robert D. Finn, Jody Clements, William Arndt, Benjamin L. Miller, Travis J. Wheeler, Fabian Schreiber, Alex Bateman, Sean R. Eddy, HMMER web server: 2015 update Nucleic Acids Research. ,vol. 43, ,(2015) , 10.1093/NAR/GKV397
Donghyuk Kim, Jay Sung-Joong Hong, Yu Qiu, Harish Nagarajan, Joo-Hyun Seo, Byung-Kwan Cho, Shih-Feng Tsai, Bernhard Ø. Palsson, Comparative Analysis of Regulatory Elements between Escherichia coli and Klebsiella pneumoniae by Genome-Wide Transcription Start Site Profiling PLoS Genetics. ,vol. 8, pp. e1002867- ,(2012) , 10.1371/JOURNAL.PGEN.1002867
S. Helaine, A. M. Cheverton, K. G. Watson, L. M. Faure, S. A. Matthews, D. W. Holden, Internalization of Salmonella by Macrophages Induces Formation of Nonreplicating Persisters Science. ,vol. 343, pp. 204- 208 ,(2014) , 10.1126/SCIENCE.1244705
Tobias Madl, Laurence Van Melderen, Natacha Mine, Michal Respondek, Monika Oberer, Walter Keller, Leila Khatai, Klaus Zangger, Structural Basis for Nucleic Acid and Toxin Recognition of the Bacterial Antitoxin CcdA Journal of Molecular Biology. ,vol. 364, pp. 170- 185 ,(2006) , 10.1016/J.JMB.2006.08.082
Longxiang Xie, Jie Zeng, Hongping Luo, Weihua Pan, Jianping Xie, The roles of bacterial GCN5-related N-acetyltransferases. Critical Reviews in Eukaryotic Gene Expression. ,vol. 24, pp. 77- 87 ,(2014) , 10.1615/CRITREVEUKARYOTGENEEXPR.2014007988
Kirsten Mattison, J. Scott Wilbur, Magdalene So, Richard G. Brennan, Structure of FitAB from Neisseria gonorrhoeae Bound to DNA Reveals a Tetramer of Toxin-Antitoxin Heterodimers Containing Pin Domains and Ribbon-Helix-Helix Motifs Journal of Biological Chemistry. ,vol. 281, pp. 37942- 37951 ,(2006) , 10.1074/JBC.M605198200
Elsa Germain, Mohammad Roghanian, Kenn Gerdes, Etienne Maisonneuve, Stochastic induction of persister cells by HipA through (p)ppGpp-mediated activation of mRNA endonucleases Proceedings of the National Academy of Sciences of the United States of America. ,vol. 112, pp. 5171- 5176 ,(2015) , 10.1073/PNAS.1423536112
Etienne Maisonneuve, Lana J. Shakespeare, Mikkel Girke Jørgensen, Kenn Gerdes, Bacterial persistence by RNA endonucleases Proceedings of the National Academy of Sciences of the United States of America. ,vol. 108, pp. 13206- 13211 ,(2011) , 10.1073/PNAS.1100186108