Regulation of an auxiliary, antibiotic-resistant tryptophanyl-tRNA synthetase gene via ribosome-mediated transcriptional attenuation.
cis-Acting RNA elements in the leaders of bacterial mRNA often regulate gene transcription, especially in the context of amino acid metabolism. We determined that the transcription of the auxiliary, antibiotic-resistant tryptophanyl-tRNA synthetase gene (trpRS1) in Streptomyces coelicolor is regulated by a ribosome-mediated attenuator in the 5' leader of its mRNA region. This regulatory element controls gene transcription in response to the physiological effects of indolmycin and chuangxinmycin, two antibiotics that inhibit bacterial tryptophanyl-tRNA synthetases. By mining streptomycete genome sequences, we found several orthologs of trpRS1 that share this regulatory element; we predict that they are regulated in a similar fashion. The validity of this prediction was established through the analysis of a trpRS1 ortholog (SAV4725) in Streptomyces avermitilis. We conclude that the trpRS1 locus is a widely distributed and self-regulating antibiotic resistance cassette. This study provides insights into how auxiliary aminoacyl-tRNA synthetase genes are regulated in bacteria.
Vecchione
James J
JJ
Department of Chemistry, Brown University, 324 Brook St., Providence, RI 02912, USA.
Sello
Jason K
JK
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001483:Base Sequence; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D008969:Molecular Sequence Data; D016296:Mutagenesis; D020125:Mutation, Missense; D012329:RNA, Bacterial / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000502:physiology*; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*; D014369:Tryptophan-tRNA Ligase / Q000235:genetics / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D012329:RNA, Bacterial; D012333:RNA, Messenger; D014369:Tryptophan-tRNA Ligase
Curr Opin Microbiol. 2008 Apr;11(2):78-86
18374625
Proc Natl Acad Sci U S A. 1979 Nov;76(11):5524-8
118451
Antimicrob Agents Chemother. 2009 Nov;53(11):4619-27
19721072
Nat Biotechnol. 2003 May;21(5):526-31
12692562
Clin Microbiol Rev. 2007 Jan;20(1):79-114
17223624
Chem Pharm Bull (Tokyo). 2001 Dec;49(12):1604-8
11767081
J Bacteriol. 2008 Jun;190(11):4050-60
18375553
J Bacteriol. 1996 Sep;178(17):5159-63
8752333
J Mol Biol. 1977 Nov 25;117(1):227-47
340702
J Biol Chem. 2002 Jun 28;277(26):23882-7
11970956
Bioessays. 2002 Aug;24(8):700-7
12210530
Adv Microb Physiol. 2000;42:47-238
10907551
Curr Drug Targets Infect Disord. 2004 Dec;4(4):261-72
15578968
Mol Microbiol. 2006 Feb;59(3):923-35
16420361
Antimicrob Agents Chemother. 2009 Sep;53(9):3972-80
19546369
J Antimicrob Chemother. 2004 Aug;54(2):549-52
15243028
Annu Rev Microbiol. 1989;43:207-33
2679354
Proc Natl Acad Sci U S A. 1973 Aug;70(8):2276-80
4209515
Mol Microbiol. 1997 Jan;23(1):169-78
9004230
J Bacteriol. 2008 Sep;190(18):6253-7
18621902
Proc Biol Sci. 2009 Jul 22;276(1667):2521-30
19364732
J Bacteriol. 2003 Sep;185(17):5320-3
12923110
Trends Genet. 2005 May;21(5):260-4
15851059
Proc Natl Acad Sci U S A. 2001 Oct 9;98(21):12215-20
11572948
Proc Natl Acad Sci U S A. 1980 Jan;77(1):508-12
6987654
Nature. 1980 Jul 31;286(5772):525-7
6250070
J Biol Chem. 2001 Jan 12;276(2):1479-85
11050092
Nucleic Acids Res. 1981 Feb 11;9(3):563-77
7012794
Mol Microbiol. 2004 May;52(4):1107-21
15130128
J Biol Chem. 2003 Mar 28;278(13):10859-78
12556463
Annu Rev Genet. 1982;16:113-34
6186194
Nature. 1981 Feb 26;289(5800):751-8
7007895
Microbiol Mol Biol Rev. 2009 Mar;73(1):36-61
19258532
Mol Microbiol. 1999 May;32(4):869-80
10361288
Mol Ecol. 1998 Sep;7(9):1205-16
9734076
Bioorg Med Chem Lett. 2002 Nov 4;12(21):3171-4
12372526
Nature. 2002 May 9;417(6885):141-7
12000953
Science. 2006 Jan 20;311(5759):374-7
16424339
J Bacteriol. 1983 Feb;153(2):1120-3
6337120
Nucleic Acids Res. 2001 Sep 1;29(17):3583-94
11522828
RNA. 2008 Apr;14(4):717-35
18359782
BMC Microbiol. 2005 Oct 03;5:54
16202131
J Bacteriol. 1966 Apr;91(4):1663
5929787