Doctor: I have some bad news andsome very bad news.Patient: Well, might as well give me thebad news first.Doctor: The lab called with your testresults. They said you have 24 hours tolive.Patient: 24 HOURS! Thats terrible!!WHAT could be WORSE? Whats the verybad news?Doctor: Ive been trying to reach you sinceyesterday.
Mycobacterium tuberculosis is theetiologic agent of tuberculosis in humans.Humans are the only reservoir for thebacterium. Mycobacterium bovis is the etiologic agentof TB in cows and rarely in humans. Both cows and humans can serve asreservoirs. Humans can also be infected by theconsumption of unpasteurized milk. This route of transmission can lead to thedevelopment of extrapulmonary TB.
ROBERT KOCH Robert koch isolated Mycobacteriumtuberculosis and proved its role in thecausation of TB
GENERAL CHARACTERISTICS Mycobacterium tuberculosis is a fairlylarge nonmotile rod-shaped bacterium. Many non pathogenic mycobacteria arecomponents of the normal flora ofhumans, found most often in dry and oilylocales. The rods are 2-4 micrometers in lengthand 0.2-0.5 um in width.
QUESTION-1 What is the Mycobacteria component that isfound in the secretions(smegma) of the genitaliaof both males and females? CLUE:it is not harmful and it’s a commensal… ANS. Mycobacterium smegmatis SIGNIFICANT POINT: This may,by its presence inurine specimens,cause confusion with tuberclebacilli
Mycobacterium tuberculosis is an obligateaerobe. For this reason, in the classic case oftuberculosis, MTB complexes are alwaysfound in the well-aerated upper lobes ofthe lungs. The bacterium is a facultativeintracellular parasite, usually ofmacrophages, and has a slow generationtime, 15-20 hours, a physiologicalcharacteristic that may contribute to itsvirulence.
QUESTION-2 IS Mycobacteriumtuberculosis A GRAM-POSITIVE OR GRAM-NEGATIVE BACTERIUM..?
Mycobacteriun tuberculosis(MTB) is notclassified as either Gram-positive orGram-negative because it does not havethe chemical characteristics ofeither, although the bacteria do containpeptidoglycan (murein) in their cell wall. If a Gram stain is performed on MTB, itstains very weakly Gram-positive or not atall (cells referred to as "ghosts").
Mycobacterium species, along withmembers of a relatedgenus Nocardia, are classifiedas acid-fast bacteria due to theirimpermeability by certain dyes andstains. Once the Mycobacteria have beenstained,they are not easilydiscolourised even with acidalcohol. This resistance to discolourisation iscalled “ACID FASTNESS” One acid-fast staining methodfor Mycobacterium tuberculosis isthe Ziehl-Neelsen stain.
When this method is used,the acid fastbacilli appear pink in contrastingbackground.
Slow generation time. Because of MTBsslow generation time, the immune systemmay not readily recognize the bacteria ormay not be triggered sufficiently toeliminate them. Many other chronic disease are caused bybacteria with slow generation times, forexample, slow-growing M. leprae causesleprosy,Treponema pallidum causessyphilis
CELL WALL STRUCTURE… The cell wall structure of Mycobacteriumtuberculosis deserves special attention because itis unique among procaryotes, and it is a majordeterminant of virulence for the bacterium. The cell wall complexcontains peptidoglycan, but otherwise it iscomposed of complex lipids. Over 60% of the mycobacterial cell wall is lipid.
Lipid fraction of MTBs cell wall consists ofthree major components, mycolicacids, cord factor, and wax-D. Mycolic acids are unique alpha-branchedlipids found in cell wallsofMycobacterium and Corynebacterium.Continues……………….
They make up 50% of the dry weight ofthe mycobacterial cell envelope. Mycolic acids are strong hydrophobicmolecules that form a lipid shellaround the organism and affectpermeability properties at the cellsurface. Mycolic Acids are thought to be asignificant determinant of virulence inMTB. Probably, they prevent attack ofthe mycobacteria by cationicproteins, lysozyme, and oxygen radicals inthe phagocytic granule. They also protect extracellularmycobacteria from complementdeposition in serum.
The high concentration of lipids in the cellwall of Mycobacterium tuberculosishavebeen associated with these properties ofthe bacterium: Impermeability to stains and dyes Resistance to many antibiotics Resistance to killing by acidic and alkalinecompounds Resistance to osmotic lysis via complementdeposition Resistance to lethal oxidations and survivalinside of macrophages
Cord factor. Cord factor (trehalose 6, 6dimycolate) is a glycolipid found in the cell wallsof mycobacteria, which causes the cells to growin serpentine cords. it blocks the macrophage activation by IFN-γ,induces secretion of TNF-ALPHA and causes MTBto form cords in vitro. Of approximately 4,000 genes inthe Mycobacterium tuberculosis genome, 525 are involved in cell wall and "cell processes", 188 genes encode regulatory proteins, 91 genes are involved in "virulence, detoxificationand adaptation". Over 200 genes are identified as encoding enzymesfor the metabolism of fatty acids.
This large number of M. tuberculosis enzymes thatputatively use fatty acids may be related to the ability ofthe pathogen to grow in the tissues of the infectedhost, where fatty acids may be the major carbon source. This is thought to be an important aspect of M.tuberculosis physiology during infection. Some of these genes and their products or activities aredescribed below.19-kDa protein. The 19-kDa protein is a secretedantigenic protein that is immunologically recognized by Tcells and sera from TB patients.. When M. tuberculosis enters macrophages and otherphagocytic cells, this surface-exposed glyco-lipoproteinis thought to cause host signaling events as it interactswith its receptor, TLR2.
LAM-LIPO ARABINO MANNAN: . LAM is a complex glycolipid that contains repeatingarabinose-mannose disaccharide subunits. It is a major component of the M. tuberculosis cellwall. It is known to be an immunomodulator analogous tothe 19-kDa protein. Addition of LAM to murine macrophages depresses IFN-gamma production. . LAM can also scavenge oxygen radicals, in vitro, andinhibits the host protein kinase C. It has been suggested that LAM functions todownregulate host immune responses to M.tuberculosis infection, to protect the bacterium frompotentially lethal mechanisms like the respiratoryburst.
TB infection means that MTB is in thebody, but the immune system is keepingthe bacteria under control. The immune system does this by producingmacrophages that surround the tuberclebacilli. The cells form a hard shell thatkeeps the bacilli contained and undercontrol. Most people with TB infection have apositive reaction to the tuberculin skintest. People who have TB infection but not TBdisease are NOT infectious, i.e., theycannot spread the infection to otherpeople. These people usually have anormal chest x-ray.
TB infection is not considered a case of TB disease. Major similarities and differences between TBinfection and TB disease are given in the tablebelow.TB INFECTION TB DISEASE IN LUNGSMTB present MTB presentTuberculin skin testpositiveTuberculin skin testpositiveChest X-ray is normal Chest X-ray reveals lesionSputum smears and cultureare negativeSputum smears and cultureare positiveNo symptoms Symptoms such ascough,fever,weight lossNot infectious Often infectious beforetreatmentNot defined as a case of TB Usually defined as a case ofTB