Mycobacterium tuberculosis

Transcription

1 Mycobacterium tuberculosis

2 Mycobacterium tuberculosis Ø small, aerobic, nonmotile bacteria Ø Gram-positive bacillus Ø can survive in a dry state for weeks Ø grow only within the cells of a host organism Ø can be cultured in the laboratory

3 Mycobacterium tuberculosis Ø spread through the air Ø typically attack the lungs, but TB bacteria can attack any part of the body such as kidney, spine & brain Ø most infections are asymptomatic and latent Ø in latent infections eventually progress to active disease Ø the classic symptoms of active TB infection are a chronic cough with blood-tinged sputum, fever, night sweats & weight loss

4 Diagnosis Active TB: radiology (x-ray), PCR, microscopic examination, microbiological culture of body fluid M. Tuberculosis (stained red) in sputum Latent TB: skin test and/or blood test

5 Tuberculosis (TB) Ø /3 of the world s population is thought to have been infected with TB Ø 3.7 million chronic active cases globally in 27 Ø in 2, there were an estimated 8.8 million new cases &.5 million associated deaths, mostly occurring in developing countries Ø no. of TB cases has been decreasing since 26, and new cases have decreased since 22 Ø distribution of TB: 8%: in Asian & Africa Ø 5-% of the US population tested positive

6 Treatment If not treated properly, TB disease can be fatal latent TB infection treatment Regimens Drugs Duration Isoniazid 9 months Isoniazid 6 months Isoniazid & Rifapentine Rifampin Interval Daily Twice weekly Daily Twice weekly Minimum doses months Once weekly 2 4 months Daily 2

7 Treatment active TB disease treatment regimens Preferred Regimen Initial Phase Alternative Regimen Alternative Regimen Initial Phase Initial Phase Daily INH, RIF, PZA, and EMB* for Thrice- weekly INH, RIF, Daily INH, RIF, PZA, and EMB* 4 doses (2 weeks), then twice PZA, and EMB* for 24 for 56 doses (8 weeks) weekly for 2 doses (6 weeks) doses (8 weeks) Continuation Phase Continuation Phase Continuation Phase Thrice- weekly INH and Daily INH and RIF for 26 Twice- weekly INH and RIF for 36 RIF for 54 doses (8 doses (8 weeks) doses (8 weeks) weeks) or Twice- weekly INH and RIF for 36 doses (8 weeks) INH: isoniazid RIF: rifampin EMB: ethambutol PZA: pyrazinamide

8 Vaccination BCG (Bacille Calmette-Guérin) Ø often given to infants & small children in countries where TB is common Ø not widely used in US Ø should only be considered for children who have a negative TB skin test

9 organism chrosome size (Mb) %GC Gene Protein 394 Mycobacterium tuberculosis F ,998 Mycobacterium tuberculosis H37Rv ,62 43 Mycobacterium tuberculosis CCDC , Mycobacterium tuberculosis CCDC , Mycobacterium tuberculosis CDC , Mycobacterium tuberculosis CTRI , 3944 Mycobacterium tuberculosis H37Ra , Mycobacterium tuberculosis H37Rv ,7 4 Mycobacterium tuberculosis KZN ,7 459 Mycobacterium tuberculosis KZN , TotalB as es : S tdeva T C ontigc ount P er.unknowns P er.l arges ts eq Myc obac terium tuberc ulos is H37R v NC _ Myc obac terium tuberc ulos is C C DC 579 NC _ Myc obac terium tuberc ulos is C C DC 58 NC _ Myc obac terium tuberc ulos is C DC 55 NC _ Myc obac terium tuberc ulos is C TR I- 2 NC _ Myc obac terium tuberc ulos is F NC _ Myc obac terium tuberc ulos is H37R a NC _ Myc obac terium tuberc ulos is H37R v NC _ Myc obac terium tuberc ulos is K ZN435 NC _ Myc obac terium tuberc ulos is K ZN427 NC _

10 M. tuberculosis CCDC579 Genome Atlas

11 replic on of c hros omes # of rr NA operons Myc obac terium tuberc ulos is H37R v NC _962 Myc obac terium tuberc ulos is C C DC 579 NC _7523 Myc obac terium tuberc ulos is C C DC 58 NC _7522 Myc obac terium tuberc ulos is C DC 55 NC _2755 Myc obac terium tuberc ulos is C TR I- 2 NC _7524 Myc obac terium tuberc ulos is F NC _9565 Myc obac terium tuberc ulos is H37R a NC _9525 Myc obac terium tuberc ulos is H37R v NC _843 Myc obac terium tuberc ulos is K ZN435 NC _2943 Myc obac terium tuberc ulos is K ZN427 NC _6768

12 Phylogenetic tree from 6S rrna alignment Myc obac terium tuberc ulos is F NC _9565 Myc obac terium tuberc ulos is H37R v NC _843 Myc obac terium tuberc ulos is C C DC 579 NC _7523 Myc obac terium tuberc ulos is K ZN427 NC _6768 Myc obac terium tuberc ulos is C DC 55 NC _2755 Myc obac terium tuberc ulos is C TR I- 2 NC _7524 Myc obac terium tuberc ulos is C C DC 58 NC _7522 Myc obac terium tuberc ulos is K ZN435 NC _2943 Myc obac terium tuberc ulos is H37R a NC _9525 Myc obac terium tuberc ulos is H37R v NC _962

13 Alignment result for 6S rrna (52 bp)

14

15 % A T % G C Myc obac terium tuberc ulos is H37R v NC _ % 65.6% Myc obac terium tuberc ulos is C C DC 579 NC _ % 65.6% Myc obac terium tuberc ulos is C C DC 58 NC _ % 65.59% Myc obac terium tuberc ulos is C DC 55 NC _ % 65.6% Myc obac terium tuberc ulos is C TR I- 2 NC _ % 65.6% Myc obac terium tuberc ulos is F NC _ % 65.62% Myc obac terium tuberc ulos is H37R a NC _ % 65.6% Myc obac terium tuberc ulos is H37R v NC _ % 65.62% Myc obac terium tuberc ulos is K ZN435 NC _ % 65.6% Myc obac terium tuberc ulos is K ZN427 NC _ % 65.6%

16 M. tuberculosis CCDC579 Amino acid & codon usage

17 # gene predic ted # gene in gbk Myc obac terium tuberc ulos is H37R v NC _ Myc obac terium tuberc ulos is C C DC 579 NC _ Myc obac terium tuberc ulos is C C DC 58 NC _ Myc obac terium tuberc ulos is C DC 55 NC _ Myc obac terium tuberc ulos is C TR I- 2 NC _ Myc obac terium tuberc ulos is F NC _ Myc obac terium tuberc ulos is H37R a NC _ Myc obac terium tuberc ulos is H37R v NC _ Myc obac terium tuberc ulos is K ZN435 NC _ Myc obac terium tuberc ulos is K ZN427 NC _

18 Blast Matrix

19 Blast Atlas F CDC55 H37Rv_962 H37Rv_843 CTRI-2 CCDC579 CCDC58 KZN427 KZN435

20 Pancore plot orgsnism Mycobacterium tuberculosis H37Rv 2 Mycobacterium tuberculosis CDC55 TotalBases gene NC_ NC_ Mycobacterium tuberculosis H37Ra 4 Mycobacterium tuberculosis F NC_ NC_ Mycobacterium tuberculosis KZN435 6 Mycobacterium tuberculosis KZN427 NC_ NC_ Mycobacterium tuberculosis CCDC58 8 Mycobacterium tuberculosis CCDC579 9 Mycobacterium tuberculosis CTRI-2 NC_ Mycobacterium tuberculosis H37Rv NC_ NC_ NC_

21 PanGome Tree Mycobacterium tuberculosis CCDC58 NC_7522 Mycobacterium tuberculosis CCDC579 NC_7523 Mycobacterium tuberculosis KZN427 NC_6768 Mycobacterium tuberculosis KZN435 NC_2943 Mycobacterium tuberculosis CTRI-2 NC_7524 Mycobacterium tuberculosis F NC_9565 Mycobacterium tuberculosis H37Rv NC_962 Mycobacterium tuberculosis H37Rv NC_843 Mycobacterium tuberculosis H37Ra NC_9525 Mycobacterium tuberculosis CDC55 NC_2755