The Transposon-Like Correia Elements Encode Numerous Strong Promoters and Provide a Potential New Mechanism for Phase Variation in the Meningococcus
Neisseria meningitidis is the primary causative agent of bacterial meningitis. The genome is rich in repetitive DNA and almost 2% is occupied by a diminutive transposon called the Correia element. Here we report a bioinformatic analysis defining eight subtypes of the element with four distinct types of ends. Transcriptional analysis, using PCR and a lacZ reporter system, revealed that two ends in particular encode strong promoters. The activity of the strongest promoter is dictated by a recurrent polymorphism (Y128) at the right end of the element. We highlight examples of elements that appear to drive transcription of adjacent genes and others that may express small non-coding RNAs. Pair-wise comparisons between three meningococcal genomes revealed that no more than two-thirds of Correia elements maintain their subtype at any particular locus. This is due to recombinational class switching between elements in a single strain. Upon switching subtype, a new allele is available to spread through the population by natural transformation. This process may represent a hitherto unrecognized mechanism for phase variation in the meningococcus. We conclude that the strain-to-strain variability of the Correia elements, and the large number of strong promoters encoded by them, allows for potentially widespread effects within the population as a whole. By defining the strength of the promoters encoded by the eight subtypes of Correia ends, we provide a resource that allows the transcriptional effects of a particular subtype at a given locus to be predicted.
Vyšlo v časopise:
The Transposon-Like Correia Elements Encode Numerous Strong Promoters and Provide a Potential New Mechanism for Phase Variation in the Meningococcus. PLoS Genet 7(1): e32767. doi:10.1371/journal.pgen.1001277
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1001277
Souhrn
Neisseria meningitidis is the primary causative agent of bacterial meningitis. The genome is rich in repetitive DNA and almost 2% is occupied by a diminutive transposon called the Correia element. Here we report a bioinformatic analysis defining eight subtypes of the element with four distinct types of ends. Transcriptional analysis, using PCR and a lacZ reporter system, revealed that two ends in particular encode strong promoters. The activity of the strongest promoter is dictated by a recurrent polymorphism (Y128) at the right end of the element. We highlight examples of elements that appear to drive transcription of adjacent genes and others that may express small non-coding RNAs. Pair-wise comparisons between three meningococcal genomes revealed that no more than two-thirds of Correia elements maintain their subtype at any particular locus. This is due to recombinational class switching between elements in a single strain. Upon switching subtype, a new allele is available to spread through the population by natural transformation. This process may represent a hitherto unrecognized mechanism for phase variation in the meningococcus. We conclude that the strain-to-strain variability of the Correia elements, and the large number of strong promoters encoded by them, allows for potentially widespread effects within the population as a whole. By defining the strength of the promoters encoded by the eight subtypes of Correia ends, we provide a resource that allows the transcriptional effects of a particular subtype at a given locus to be predicted.
Zdroje
1. HarrisonLH
TrotterCL
RamsayME
2009 Global epidemiology of meningococcal disease. Vaccine 27 Suppl 2 B51 63
2. SultanB
LabadiK
GueganJF
JanicotS
2005 Climate drives the meningitis epidemics onset in west Africa. PLoS Med 2 e6 doi:10.1371/journal.pmed.0030006
3. BentleySD
VernikosGS
SnyderLA
ChurcherC
ArrowsmithC
2007 Meningococcal genetic variation mechanisms viewed through comparative analysis of serogroup C strain FAM18. PLoS Genet 3 e23 doi:10.1371/journal.pgen.0030023
4. DavidsenT
TonjumT
2006 Meningococcal genome dynamics. Nat Rev Microbiol 4 11 22
5. ParkhillJ
AchtmanM
JamesKD
BentleySD
ChurcherC
2000 Complete DNA sequence of a serogroup A strain of Neisseria meningitidis Z2491. Nature 404 502 506
6. TettelinH
SaundersNJ
HeidelbergJ
JeffriesAC
NelsonKE
2000 Complete genome sequence of Neisseria meningitidis serogroup B strain MC58. Science 287 1809 1815
7. CorreiaFF
InouyeS
InouyeM
1986 A 26-base-pair repetitive sequence specific for Neisseria gonorrhoeae and Neisseria meningitidis genomic DNA. J Bacteriol 167 1009 1015
8. CorreiaFF
InouyeS
InouyeM
1988 A family of small repeated elements with some transposon-like properties in the genome of Neisseria gonorrhoeae. J Biol Chem 263 12194 12198
9. BuisineN
TangCM
ChalmersR
2002 Transposon-like Correia elements: structure, distribution and genetic exchange between pathogenic Neisseria sp. FEBS Lett 522 52 58
10. Claeys BouuaertC
ChalmersRM
2010 Gene therapy vectors: the prospects and potentials of the cut-and-paste transposons. Genetica 138 473 484
11. Claeys BouuaertC
ChalmersR
2010 Transposition of the human Hsmar1 transposon: rate-limiting steps and the importance of the flanking TA dinucleotide in second strand cleavage. Nucleic Acids Res 38 190 202
12. Munoz-LopezM
SiddiqueA
BischerourJ
LoriteP
ChalmersR
PalomequeT
2008 Transposition of Mboumar-9: identification of a new naturally active mariner-family transposon. J Mol Biol 382 567 572
13. LiuD
BischerourJ
SiddiqueA
BuisineN
BigotY
ChalmersR
2007 The human SETMAR protein preserves most of the activities of the ancestral Hsmar1 transposase. Mol Cell Biol 27 1125 1132
14. AzizRK
BreitbartM
EdwardsRA
2010 Transposases are the most abundant, most ubiquitous genes in nature. Nucleic Acids Res 38 4207 4217
15. ChalmersR
BlotM
1999 Insertion Sequences and Transposons.
CharleboisRL
Organization of the Prokaryotic Genome Washington, D.C. American Society for Microbiology 151 169
16. SchmidtJM
GoodRT
AppletonB
SherrardJ
RaymantGC
2010 Copy number variation and transposable elements feature in recent, ongoing adaptation at the Cyp6g1 locus. PLoS Genet 6 e1000998 doi:10.1371/journal.pgen.1000998
17. MahillonJ
ChandlerM
1998 Insertion sequences. Microbiol Mol Biol Rev 62 725 774
18. SimonsRW
HoopesBC
McClureWR
KlecknerN
1983 Three promoters near the termini of IS10 - pIN, pOUT, and pIII. Cell 34 673 682
19. GlansdorffN
CharlierD
ZafarullahM
1981 Activation of gene expression by IS2 and IS3. Cold Spring Harb Symp Quant Biol 45 Pt 1 153 156
20. HintonDM
MussoRE
1982 Transcription initiation sites within an IS2 insertion in a Gal-constitutive mutant of Escherichia coli. Nucleic Acids Res 10 5015 5031
21. PrentkiP
TeterB
ChandlerM
GalasDJ
1986 Functional promoters created by the insertion of transposable element IS1. J Mol Biol 191 383 393
22. LiuSV
SaundersNJ
JeffriesA
RestRF
2002 Genome analysis and strain comparison of Correia repeats and Correia repeat-enclosed elements in pathogenic Neisseria. J Bacteriol 184 6163 6173
23. De GregorioE
AbresciaC
CarlomagnoMS
Di NoceraPP
2002 The abundant class of nemis repeats provides RNA substrates for ribonuclease III in Neisseriae. Biochim Biophys Acta 1576 39 44
24. De GregorioE
AbresciaC
CarlomagnoMS
Di NoceraPP
2003 Ribonuclease III-mediated processing of specific Neisseria meningitidis mRNAs. Biochem J 374 799 805
25. MazzoneM
De GregorioE
LavitolaA
PagliaruloC
AlifanoP
Di NoceraPP
2001 Whole-genome organization and functional properties of miniature DNA insertion sequences conserved in pathogenic Neisseriae. Gene 278 211 222
26. FrancisF
Ramirez-ArcosS
SalimniaH
VictorC
DillonJR
2000 Organization and transcription of the division cell wall (dcw) cluster in Neisseria gonorrhoeae. Gene 251 141 151
27. BlackCG
FyfeJA
DaviesJK
1995 A promoter associated with the neisserial repeat can be used to transcribe the uvrB gene from Neisseria gonorrhoeae. J Bacteriol 177 1952 1958
28. PackiamM
ShellDM
LiuSV
LiuYB
McGeeDJ
2006 Differential expression and transcriptional analysis of the alpha-2,3-sialyltransferase gene in pathogenic Neisseria spp. Infect Immun 74 2637 2650
29. ZhaoS
MontanezGE
KumarP
SannigrahiS
TzengYL
2010 Regulatory role of the MisR/S two-component system in hemoglobin utilization in Neisseria meningitidis. Infect Immun 78 1109 1122
30. KumarA
MallochRA
FujitaN
SmillieDA
IshihamaA
HaywardRS
1993 The minus 35-recognition region of Escherichia coli sigma 70 is inessential for initiation of transcription at an “extended minus 10” promoter. J Mol Biol 232 406 418
31. SwartleyJS
AhnJH
LiuLJ
KahlerCM
StephensDS
1996 Expression of sialic acid and polysialic acid in serogroup B Neisseria meningitidis: divergent transcription of biosynthesis and transport operons through a common promoter region. J Bacteriol 178 4052 4059
32. PonnambalamS
WebsterC
BinghamA
BusbyS
1986 Transcription initiation at the Escherichia coli galactose operon promoters in the absence of the normal −35 region sequences. J Biol Chem 261 16043 16048
33. AzamTA
IwataA
NishimuraA
UedaS
IshihamaA
1999 Growth phase-dependent variation in protein composition of the Escherichia coli nucleoid. J Bacteriol 181 6361 6370
34. DittoMD
RobertsD
WeisbergRA
1994 Growth phase variation of integration host factor level in Escherichia coli. J Bacteriol 176 3738 3748
35. KingsfordCL
AyanbuleK
SalzbergSL
2007 Rapid, accurate computational discovery of rho-independent transcription terminators illuminates their relationship to DNA uptake. Genome Biol 8 R22
36. GottesmanS
2002 Stealth regulation: biological circuits with small RNA switches. Genes Dev 16 2829 2842
37. GottesmanS
2004 The small RNA regulators of Escherichia coli: roles and mechanisms*. Annu Rev Microbiol 58 303 328
38. ArgamanL
HershbergR
VogelJ
BejeranoG
WagnerEGH
MargalitH
AltuviaS
2001 Novel small RNA-encoding genes in the intergenic regions of Escherichia coli. Curr Biol 11 941 950
39. ChenS
LesnikEA
HallTA
SampathR
GriffeyRH
EckerDJ
BlynLB
2002 A bioinformatics based approach to discover small RNA genes in the Escherichia coli genome. BioSystems 65 157 177
40. VogelJ
SharmaCM
2005 How to find small non-coding RNAs in bacteria. Biol Chem 386 1219 1238
41. EnriquezR
AbadR
ChantoG
CorsoA
CrucesR
2010 Deletion of the Correia element in the mtr gene complex of Neisseria meningitidis. J Med Microbiol 59 1055 1060
42. SnyderLA
ShaferWM
SaundersNJ
2003 Divergence and transcriptional analysis of the division cell wall (dcw) gene cluster in Neisseria spp. Mol Microbiol 47 431 442
43. SwingerKK
RicePA
2004 IHF and HU: flexible architects of bent DNA. Curr Opin Struct Biol 14 28 35
44. DormanCJ
2009 Nucleoid-associated proteins and bacterial physiology. Adv Appl Microbiol 67 47 64
45. Rouquette-LoughlinCE
BalthazarJT
HillSA
ShaferWM
2004 Modulation of the mtrCDE-encoded efflux pump gene complex of Neisseria meningitidis due to a Correia element insertion sequence. Mol Microbiol 54 731 741
46. ShaJ
KozlovaEV
FadlAA
OlanoJP
HoustonCW
PetersonJW
ChopraAK
2004 Molecular characterization of a glucose-inhibited division gene, gidA, that regulates cytotoxic enterotoxin of Aeromonas hydrophila. Infect Immun 72 1084 1095
47. ChoKH
CaparonMG
2008 tRNA modification by GidA/MnmE is necessary for Streptococcus pyogenes virulence: a new strategy to make live attenuated strains. Infect Immun 76 3176 3186
48. CarpousisAJ
2003 Degradation of targeted mRNAs in Escherichia coli: regulation by a small antisense RNA. Genes Dev 17 2351 2355
49. HandNJ
SilhavyTJ
2000 A practical guide to the construction and use of lac fusions in Escherichia coli. Methods Enzymol 326 11 35
50. MillerJH
1972 Experiments in Molecular genetics Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY
51. SawayaR
ArhinFF
MoreauF
CoultonJW
MillsEL
1999 Mutational analysis of the promoter region of the porA gene of Neisseria meningitidis. Gene 233 49 57
52. SimonsRW
HoumanF
KlecknerN
1987 Improved single and multicopy lac-based cloning vectors for protein and operon fusions. Gene 53 85 96
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2011 Číslo 1
- Gynekologové a odborníci na reprodukční medicínu se sejdou na prvním virtuálním summitu
- Je „freeze-all“ pro všechny? Odborníci na fertilitu diskutovali na virtuálním summitu
Najčítanejšie v tomto čísle
- H3K9me-Independent Gene Silencing in Fission Yeast Heterochromatin by Clr5 and Histone Deacetylases
- Rnf12—A Jack of All Trades in X Inactivation?
- Joint Genetic Analysis of Gene Expression Data with Inferred Cellular Phenotypes
- Evolutionary Conserved Regulation of HIF-1β by NF-κB