Mycobacterium tuberculosis

Mycobacterium tuberculosis

Presented by Katherine SawyerFor BIOL 306 Genome Project

October 14, 2009

Mycobacterium tuberculosisPresented by Katherine Sawyer

1. How many nucleotides, genes, and chromosomes are in the Mycobacterium tuberculosis genome?

2. Why is it important to study the M. tuberculosis genome?

3. What are 2 recent research findings related to the M. tuberculosis genome?

Mycobacterium tuberculosis facts:Type of organism: bacillus (rod-

shaped) bacteria (eubacteria)

Lineage [NCBI Taxonomy]: Cellular organisms;  Bacteria; Actinobacteria; Actinobacteria(class);  Actinobacteridae;  Actinomycetales;  Corynebacterineae; Mycobacteriaceae;  Mycobacterium;  Mycobacterium tuberculosis compl

ex; 

Mycobacterium tuberculosis

M. Tuberculosis infection (M. tuberculosis are pink rods)

Image from http://library.med.utah.edu/WebPath/INFEHTML/INFEC033.html

.Image from  Centers for Disease Control and Prevention ( public domain.)

More M. tuberculosis facts

According to CDC, 1/3 of the world’s population are infected with TB.

Each year, nearly 9 million people around the worldbecome sick with TB and almost 2 million die from illness caused by M. tuberculosis

TB is the primary cause of death of people who are HIV infected.

Some strains are multi-drug resistant Most common strains lead to respiratory and lung

disease, some strains can also affect brain (meningitis), liver, and other organs

W.H.O. Map of New TB cases, 2006image from

http://gamapserver.who.int/mapLibrary/Files/Maps/Global_EstimatedTB_ITHRiskMap.png

M. tuberculosis infection

Left image From http://www.nlm.nih.gov/medlineplus/ency/imagepages/1607.htm Right image from http://www.nlm.nih.gov/medlineplus/ency/imagepages/1034.htm

M. tuberculosis genome

Over 70 identified strains First sequenced was H36Rv: 4,411, 529 bp T46: 4,347,699 bp Average bp = approximately 4.4 Mbp

4183 Genes 1 chromosome Large genome for a bacteria, slightly smaller

than E. coli

Genome size comparison with other bacteria

0

1

2

3

4

5

Genome Size (Mbp)

Streptococcuspneumoniae

Mycobacteriumtuberculosis

Escherichiacoli

Genome size comparison with other organisms

24 5

180

3000

1

10

100

1000

10000

Genome size (Mbp)

Streptococcuspneumoniae

Mycobacteriumtuberculosis

Esherichia coli

Drosophilamelanogaster

Homo sapien

M. tuberculosis genome research First complete sequence project in 1998 by

Wellcome Trust Sanger Institute. (whole genome shotgun sequencing method).

(Fleishman, et al, 2002) Genetic variation between strains was more than expected, including long sequence polymorphism.

(Caws, et al, 2008) Both the host and the bacterial genome affect the disease process. There are specific strains adapted to specific human populations

Why did I choose this M. tuberculosis? Understanding of M. tuberculosis makes better drug

development possible. Successful drug therapy for this disease could benefit millions of people.

Bioinformatics play a key role in comparing the huge variety of strains of this bacteria in addition to the sequencing process itself.

Mycobacterium tuberculosisPresented by Katherine Sawyer

1. How many nucleotides, genes, and chromosomes are in the Mycobacterium tuberculosis genome?

2. Why is it important to study the M. tuberculosis genome?

3. What are 2 recent research findings related to the M. tuberculosis genome?

References: complete genomes Cole S. T., Brosch R., Parkhill J., Garnier T., Churcher C., Harris D., Gordon Cole S. T., Brosch R., Parkhill J., Garnier T., Churcher C., Harris D., Gordon

S. V., Eiglmeier K., Gas S., Barry III C.E., et al., (1998) Deciphering the S. V., Eiglmeier K., Gas S., Barry III C.E., et al., (1998) Deciphering the biology of biology of Mycobacterium tuberculosisMycobacterium tuberculosis from the complete genome from the complete genome sequence. sequence. Nature Nature 393: 190-198, 537-544393: 190-198, 537-544..

http://www.ncbi.nlm.nih.gov/nuccore/NC_002755?ordinalpos=1&itool=EntrezSystem2.PEntrez.Sequence.Sequence_ResultsPanel.Sequence_RVDocSum

http://www.ncbi.nlm.nih.gov/nuccore/NC_009565?ordinalpos=1&itool=EntrezSystem2.PEntrez.Sequence.Sequence_ResultsPanel.Sequence_RVDocSum

http://www.ncbi.nlm.nih.gov/nuccore/NC_009525?ordinalpos=1&itool=EntrezSystem2.PEntrez.Sequence.Sequence_ResultsPanel.Sequence_RVDocSum

http://www.ncbi.nlm.nih.gov/nuccore/NC_012943?ordinalpos=1&itool=EntrezSystem2.PEntrez.Sequence.Sequence_ResultsPanel.Sequence_RVDocSum

Other references

Smith, I. Smith, I. Mycobacterium tuberculosisMycobacterium tuberculosis Pathogenesis and Molecular Determinants of Virulence (2003 July)  Pathogenesis and Molecular Determinants of Virulence (2003 July) Clinical Microbiology ReviewClinical Microbiology Review 16(3): 463-496. 16(3): 463-496.

Caws M., Thwaites G., Dunstan S., Hawn T.R., Lan N.T.N. , Thuong N.T.T., Stepniewska K., Huyen M.G.T., Caws M., Thwaites G., Dunstan S., Hawn T.R., Lan N.T.N. , Thuong N.T.T., Stepniewska K., Huyen M.G.T., Bang N.D., Loc T.H., et al.. (2008) The Influence of Host and Bacterial Genotype on the Development of Bang N.D., Loc T.H., et al.. (2008) The Influence of Host and Bacterial Genotype on the Development of Disseminated Disease with Disseminated Disease with Mycobacterium tuberculosis. Mycobacterium tuberculosis. Public Library of Science (PLoS) Public Library of Science (PLoS) PathogensPathogens 4(3) 4(3) e100004.e100004.

Fleischmann, RD, Allnad D, Eisen, JA, Carpenter L, White, O, Peterson, R., Deboy, R, Dodson, R, Gwinn, Fleischmann, RD, Allnad D, Eisen, JA, Carpenter L, White, O, Peterson, R., Deboy, R, Dodson, R, Gwinn, M, Haft, D., Hickey, E, Kolonay, JF, Nelson, WC, Umayam, A, Ermolaeva, M, Salzberg, SL, Delcher, A, M, Haft, D., Hickey, E, Kolonay, JF, Nelson, WC, Umayam, A, Ermolaeva, M, Salzberg, SL, Delcher, A, Utterback, T. , Weidman, J. Khouri, H. Gill, J, Mikula, A., Bishai, W. Jacobs, WR, Venter, JC, and Fraser, Utterback, T. , Weidman, J. Khouri, H. Gill, J, Mikula, A., Bishai, W. Jacobs, WR, Venter, JC, and Fraser, CM, (2002) Whole Genome Comparison of CM, (2002) Whole Genome Comparison of Mycobacterium tuberculosis Mycobacterium tuberculosis Clinical and Laboratory Strains. Clinical and Laboratory Strains. Journal of BacteriologyJournal of Bacteriology 184 (19) : 5479-5490. 184 (19) : 5479-5490.

http://www.ncbi.nlm.nih.gov/sites/entrez?Db=genomeprj&cmd=ShowDetailView&TermToSearch=224http://www.ncbi.nlm.nih.gov/sites/entrez?Db=genomeprj&cmd=ShowDetailView&TermToSearch=224

http://library.med.utah.edu/WebPath/TUTORIAL/MTB/MTB.html

http://www.cdc.gov/tb/

http://gamapserver.who.int/mapLibrary/Files/Maps/Global_EstimatedTB_ITHRiskMap.png